Revision Notes for MMed Neurosurgery (UoN

Revision Notes in Scientific Principles of Surgery for MMed Neurosurgery (UoN)
Prof N J M Mwangombe, Professor of Surgery, University of Nairobi

Kenyatta National Hospital, Nairobi, Kenya.
Every man/woman owes it as a debt to his/her profession to put on record

whatever he/she has done that might be of use for others.
Francis Bacon (1561-1626)
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TABLE OF CONTENTS
Topic Page
Foreword 3
Pre-op Assessment and Preparation of the Surgical Patient 4
Management of Medical Conditions in Surgical Patients 13
Metabolic response to trauma 16
Surgical nutrition 20
Fluid and Electrolyte Balance 35
Fluid Management in Paeditric Surgery 43
Shock 48
Disorders of Acid Base Balance in Surgery 65
Incisions and Wound Closure 74
Post-operative complications 79
General Surgical Infections 81
Surgical Site Infections 100
Gas embolism 113
Deep Venous Thrombosis 119
Pulmonary and Fat Embolism 127
Compartment Syndrome 133
Bleeding in the Surgical Patient 135
Blood and Blood Products 139
Septic Shock, SIRS, MODS, ARDS 150
Principles of Surgical Oncology 161
Surgery Clerkship Manual 186
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FOREWORD
The Department of Surgery, School of Medicine, University of Nairobi,
introduced a 6-year postgraduate training program in the speciality of
neurosurgery in 2006. At that time, Kenya had only 14 neurosurgeons. The
aim of the training program was to meet the needs of the country in line with
the National Health Policy Framework, 2012-2030, and Vision 2030, and
establish neurosurgical services in all level 5 and 6 hospitals in Kenya.
The first two years of training are based on the Common Foundation
Principles of Surgery that apply to all surgical specialities. The MMed
Neurosurgery (MMedNS) program was the pioneer program at the University
of Nairobi to undertake this Foundation Course. I was privileged to introduce
and teach this course during that period. The revision notes are a collection of
the lectures I gave during that period.
Any part of this document may be partially or fully reproduced, quoted and
used, provided the source is acknowledged. However, it cannot be used for
profit or other commercial purposes.
Comments and inquiries from readers and users are welcome.
Prof Nimrod Juniahs Mwakitawha Mwangombe MBChB, MMed, PhD (Lond)

Department of Surgery, University of Nairobi
PO Box 19676-0020
Nairobi, Kenya.
3
CHAPTER 1
PRE-OPERATIVE ASSESSMENT AND PREPARATION OF THE SURGICAL

PATIENT.
Aims to:
(i) reduce morbidity and mortality associated with surgery
(ii) prevent unnecessary cancellations
(iii) reduce hospital stay
Plan:
(i) inform patient of the proposed procedure, time of admission and starving
instructions, transport to theatre, anesthesia, duration of surgery, recovery
period, postoperative drains or catheters, postoperative care, discharge date,
follow up, likely date of return to work or full activity
(ii) obtain informed consent for the procedure
(iii) assess pre-existing medical conditions and manage usual medication and
specific pre-operative preparation
(iv) plan pre and postoperative management of these conditions
Perform a pre-operative examination of patient for medical conditions

associated with increased morbidity and mortality:
(i) Ischaemic heart disease
(ii) (ii) Congestive cardiac failure
(iii) Hypertension
(iv) Cardiac arrhythmias
(v) Chronic respiratory disease
(vi) Diabetes mellitus
(vii) Endocrine dysfunction
(viii) Chronic renal failure
(ix) Nephrotic syndrome
(x) Obstructive jaundice
Table 1. Indications for preoperative investigations
Investigation Indication
(i) Full blood count Routine
(ii)Urea and electrolytes Routine
(iii) ECG Men over 40 years
Women over 50 years
Cardiovascular disease
Diabetics
(iv) Chest X-ray Routine
Pre-operative investigations cannot screen for asymptomatic disease and

rarely uncover unsuspected medical conditions.
The National Institute for Clinical Excellence (NICE) guidelines on

preoperative tests recommend the following tests, as and when required
4
based on clinical judgement, age, ASA Grade of patient and Grade of
surgery. Avoid unnecessary pre-operative investigations:
(i) Chest x-ray
(ii) ECG
(iii) Full blood count
(iv) Clotting screen
(v) Renal function
(vi) Random blood glucose
(vii) Urinalysis
(viii) Blood gases
(ix) Lung function tests
Important factors in doctor-patient relationship and patient management

(i) Concern for the patients views, privacy and care
(ii) Provide patient with relevant information on illness
(iii) Keep your professional knowledge and skills up to date and
recognise your professional limits
(iv) Respect patient confidentiality
(v) Avoid abusing position as a doctor
(vi) Work with colleagues when necessary to promote patient care
Informed consent
(i) Respect patients autonomy and right to decide
(ii) Provide sufficient information on illness and treatment to the patient
Types of consent
(i) Express consent - oral or written. Needed for most investigations or
treatments with risks attached e.g. consent for operation
(ii) Implied consent. Non-written consent when patient co-operates with
a particular action e.g. physical examination
Information required for valid consent:

(i) diagnosis and prognosis with and without treatment
(ii) other treatment options
(iii) Purpose, benefit and probability of success of proposed treatment
(iv) possible side effects
(v) right of the patient to change his/her mind and obtain second
opinion
In an emergency a life-saving procedure can be performed without consent

from patient, consent being given by the consultant involved in the
management of the patient.
A parent may authorise treatment when the child is below 18 years of age.
Premedication: administration of drugs prior to an anaesthetic. Has three

potentially useful effects:
5
(i) Anxiolysis. Anxiolysis if needed can be achieved with either
benzodiazepines or phenothiazines. Opiate analgesics also have
useful sedative properties
(ii) Reduced bronchial secretions. Reduction of secretions is not as
important today with modern inhalational agents. Ether was
notorious for stimulating bronchial secretions. If required secretions
can be reduced with hyoscine. Also reduce salivation and prevents
bradycardia.
(iii) Analgesia. Analgesia best achieved with strong opiates
Drugs used in premedication should be able to achieve the following;

Anxiolysis - benzodiazepines, phenothiazines
Analgesia - opiates, non-steroids anti-inflammatories
Amnesia - benzodiazepines, anticholinergics
Antiemetic - anticholinergics, antihistamines, 5HT antagonist
Antacid - Alginates, proton pump inhibitors
Anti-autonomic - anticholinergics, beta-blockers
Adjuncts - Bronchodilators, steroids
Induction. Induction agents are usually administered intravenously and

distributed to organs with a high blood flow (e.g. brain).
Should be highly lipid soluble, rapidly cross blood brain barrier
and be redistributed from brain
Should have rapid onset and rapid recovery
(i) Thiopentone. Short-acting barbiturate. First used at Pearl Harbour
in 1942. Depresses myocardium. In hypovolaemic patient can
induce profound hypotension
(ii) Propofol. Has very short half-life. Can cause hypotension. Can also
be used for maintenance of anaesthesia as an infusion
Rapid induction of anaesthesia.

Cricoid pressures used to reduce risk of aspiration
Pressure released once tracheal intubation with a cuffed tube has been
achieved
Achieved by the use of thiopentone and suxamethonium. Ideal for following
patients
(i) None fasted.
(ii) History of gastro-oesophageal reflux
(iii) Emergency trauma patients
(iv) Intestinal obstruction
(v) Pregnancy
(vi) Intra-abdominal pathology that will delay gastric emptying
RISK ASSESSMENT AND MANAGEMENT

Risk assessment forms an integral part of patient care.
An assessment needs to be made of the risks vs. benefits for any surgery.
These will then influence decisions made by the surgeon or the patient.
6
Assessment of risk in surgery depends on knowledge of the following factors;
patient, disease, comorbidities, proposed surgery and physiological status.
Risk assessment tools:
(i) ASA Grading
(ii) Injury Severity Score
(iii) Revised Trauma score
(iv) Tests of Respiratory, Cardiac and Renal Disease
ASA Grading
Medical co-morbidity increases the risk associated with anaesthesia and
surgery.
American Society of Anesthesiologists (ASA) grade is the most commonly
used grading system. ASA grade can accurately predict morbidity and
mortality.
Normally 50% of patients presenting for elective surgery are ASA grade 1 and
therefore low risk. Operative mortality for these patients is less than 1 in
10,000
Table 2. American Society of Anesthesiologists (ASA) Classification of Physical Status
ASA Grade Definition Mortality (%)

I Normal healthy individual 0.05
II Mild systemic disease that does not limit activity 0.4
III Severe systemic disease that limits activity but is not incapacitating 4.5
IV Incapacitating systemic disease which is constantly life-threatening 25
V Moribund, not expected to survive 24 hours with or without surgery 50
Table 3. Application of ASA Grading. Cardiovascular disease
ASA Grade 2 ASA Grade 3

Angina Occasional use of GTN Regular use of GTN or unstable angina
Hypertension Well controlled on single agent Poorly controlled. Multiple drugs
Diabetes Well controlled. No complications Poorly controlled or complications
GTN=glyceryl trinitrate
Table 4. Application of ASA Grading. Respiratory disease
ASA Grade 2 ASA Grade 3

COPD Cough or wheeze. Well controlled Breathless on minimal exertion
Asthma Well controlled with inhalers Poorly controlled. Limiting lifestyle
COPD=chronic obstructive pulmonary disease
ABBREVIATED INJURY SCALE (AIS) AND INJURY SEVERITY SCORE

(ISS)
Used to assess patients involved in traffic accidents with multiple injuries.
The Abbreviated Injury Scale is an anatomical scoring system first introduced
in 1969. Injuries are ranked on a scale of 1 to 6, with 1 being minor, 5 severe
and 6 a nonsurvivable injury. This represents the 'threat to life' associated
with an injury and is not meant to represent a comprehensive measure of
severity.
7
Injury AIS score

1 Minor
2 Moderate
3 Serious
4 Severe
5 Critical
6 Unsurvivable
The Injury Severity Score (ISS) is an anatomical scoring system that provides
an overall score for patients with multiple injuries. Each injury is assigned an
AIS and is allocated to one of six body regions (Head, Face, Chest, Abdomen,
Extremities (including Pelvis), External). Only the highest AIS score in each
body region is used. The 3 most severely injured body regions have their
score squared and added together to produce the ISS score.
Its value correlates with the risk of mortality.
Patients with immediately or rapidly fatal injuries are excluded (AIS score 6)
Injuries are assigned to six body regions
1. Head and neck
2. Face
3. Chest,
4. Abdomen,
5. Extremities & pelvis
6. External
Each type of injury encountered is assigned a value from 1 to 5;
Minor injury = 1
Moderate injury = 2
Severe but not life-threatening injury = 3
Life-threatening but survival likely = 4
Critical with uncertain survival = 5
Table 5. Examples of AIS scores
System Example AIS Square

top 3
General 1st degree burns 1 1
General 50% 3rd degree burns 3 9
Chest Haemothorax 3 9
Chest Pericardial injury/flail chest 4 16
Abdomen Ruptured liver/spleen 5 25
Contusion liver 2 4
Extremity Fractured femur 3 9
Head and neck Cerebral contusion 3 9
Face No injury 0 0
Injury severity score 50
Highest score, indicating the most severe injury, for each region is selected.
Ranked from the highest to lowest value.
Three highest values are then used to calculate the injury severity score.
8
Injury severity score (ISS) = square of highest region score + square of
second highest region score + square of third highest region score
Minimum score: 0
Maximum score: 75
Mortality rate increases with score and age
Table 6. Mortality (%) according to ISS and age
ISS Mortality (%) Mortality (%) Mortality (%)

Score <49 yrs 50-69 yrs > 70 yrs
5 0 3 13
10 2 4 15
15 3 5 16
20 6 16 31
25 9 26 44
30 21 42 65
35 31 56 82
40 47 62 92
45 61 67 100
50 75 83 100
55 89 100 100
REVISED TRAUMA SCORE

The Revised Trauma Score (RTS) is a physiological scoring system, with high
inter-rater reliability and demonstrated accuracy in predicting death. It is
scored from the first set of data obtained on the patient, and consists of
Glasgow Coma Scale, Systolic Blood Pressure and Respiratory Rate.
Revised trauma score = (points for respiratory rate) + (points for systolic blood
pressure) + (points for Glasgow coma score)
Maximum score (indicating least affected) = 12
Minimum score (indicating most affected) = 0
Used to rapidly assess patients at the scene of an accident
Table 7. Revised Trauma Score
Parameter Finding Points

Respiratory rate 10-29 per minute 4
> 29 per minute 3
6-9 per minute 2
1-5 per minute 1
Nil 0
Systolic blood pressure >89 mmHg 4
76-89 mm Hg 3
50-75 mm Hg 2
1-49 mm Hg 1
Nil 0
Glasgow Coma Score 13-15 4
9-12 3
6-8 2
4-5 1
3 0
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TESTS OF RESPIRATORY, CARDIAC AND RENAL DISEASE

Respiratory function
Lung function tests should be able to predict the type and severity of lung
disease
Can predict risk of complications and postoperative mortality
Tests fall in to three categories
i) Lung mechanics
ii) Gas exchange
iii) Control of breathing
Useful radiological investigations include chest x-ray and high-resolution

thoracic CT
Arterial blood gases may at times be needed
Lung function tests assess lung volumes, airway calibre and gas transfer
a) Spirometry: Lung volumes are assessed with spirometry

Volumes measured include:
IC = Inspiratory capacity
IRV = Inspiratory reserve volume
TV = Tidal volume
VC = Vital capacity
FRC = Functional residual capacity
RV = Residual volume
ERV = Expiratory reserve volume
TLC = Total lung capacity
b) Peak flow rates: Airway calibre can be assessed with peak flow
measurements
Requires co-operation and maximum voluntary effort of the patient
Flow rates measured include
FVC = Forced vital capacity
FEV1 = Forced expiratory volume in one second
Absolute values depend on height, weight, age, sex and race
FEV1 / FVC ratio is important
c) Gas transfer: Arterial blood gases are best measure available of gas
transfer
Also allow assessment of ventilation / perfusion mismatch
Important parameters to measure are: pH, Partial pressure of oxygen, Partial
pressure of carbon dioxide.
Pulse oximetry gives an indirect estimate of gas transfer. Technique is
unreliable in the presence of other medical problems (e.g. anaemia)
Lung function can be classified as:

i) Normal
10
ii) Restrictive
ii) Obstructive
In restrictive lung disease FVC is reduced but FEV1/FVC is normal
In obstructive lung disease FVC is normal or reduced and FEV1/FVC is
reduced
Cardiac function
Simple non-invasive and more complicated invasive tests of cardiac function
exist
Non-invasive: Chest x-ray, ECG, Echocardiography, Exercise test.
Invasive: Coronary angiography, Thallium scanning
Chest x-ray
Routine chest x-ray is not recommended
It is indicated in the presence of cardiorespiratory symptoms or signs
Important signs associated with increased cardiac morbidity are:
cardiomegaly, pulmonary oedema and change in the cardiac outline
characteristic of specific diseases
ECG
Resting ECG is normal in 25-50% of patients with ischaemic heart disease.
Characteristic features of ischaemia or previous infarction may be present.
Exercise ECG provides a good indication of the degree of cardiac reserve.
24-hour monitoring is useful in the detection and assessment of arrhythmias
Echocardiography
Can be performed percutaneously or transoesophageal.
Two-dimensional echocardiography allows assessment of muscle mass,
ventricular function / ejection fraction, end-diastolic and end-systolic volumes,
valvular function,
segmental defects
Doppler ultrasound
Allows assessment of valvular flow and pressure gradients
Nuclear medicine
Myocardial scintigraphy allows assessment of myocardial perfusion.
Radiolabelled thallium is commonest isotope used.
Areas of ischaemia or infarction appear as 'cold' spots.
Vasodilators can be used to evaluate reversibility of ischaemia.
Radiolabelled albumin or red cells can be used to assess ejection fraction.
Renal function
Glomerular filtration rate is the gold standard test of renal function.
Can be calculated by measuring creatinine clearance rate.
Requires 24-hour urine collection.
Serum creatinine allows a good estimate of renal function.
Use of serum creatinine may be inaccurate in patients with obesity, oedema,
pregnancy and ascites.
OUTCOME ASSESSMENT IN NEUROSURGERY

(i) The Karnofsky outcome scale for malignancy
11
Table 8. Karnofsky scale
Score Observation
100 Normal
90 minor symptoms
80 symtoms and activity with effort
70 cares for self without normal activity
60 requires assistance
50 requires care
40 Disabled
30 severly disabled, hospitalised
20 very sick on active support
10 Moribund
0 Dead
(ii) The Glasgow outcome scale for head injuries
Table 9 Glasgow outcome scale
Score Observation
5 good recovery
4 moderate disability
3 severe disability
2 vegetative state
1 Death
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CHAPTER 2
MANAGEMENT OF MEDICAL CONDITIONS IN SURGICAL PATIENTS
The following conditions may increase anaesthetic risk to the patient;

difficult airway, obesity, cardiac disease, respiratory disease, gastrointestinal
disease, renal failure, diabetes, haematological disorders, allergic reactions.
(I). Cardiovascular disease.

Hypertension, ischaemic heart disease, cerebrovascular disease, deep
venous thrombosis, difficult vascular access.
Cardiac risk assessment in surgery:
Several scoring systems exist for stratifying cardiac risk prior to non-cardiac
surgery.
Simple to use and identify patients in need of further investigation
(a). Eagle index
One point allocated for each of the following:
i) History of myocardial infarction of angina
ii) Q wave on preoperative ECG
iii) Non-diet controlled diabetes mellitus
iv) Age more than 70 years
v) History of ventricular arrhythmia
If total score is:
No points = low risk
1 or 2 points = intermediate risk
More than 2 points = high risk
Low risk patients require no further investigation
Intermediate risk patients require exercise ECG and thallium scan
High risk patients require coronary angiography prior to major surgery
(b). Revised cardiac risk index
One point allocated for each of the following:
i) High-risk surgery
ii) Ischaemic heart disease
iii) History of congestive heart failure
iv) History of cerebrovascular disease
v) Insulin therapy for diabetes mellitus
vi) Renal impairment
vii) Risk of major cardiac event during surgery:
No points = 0.5% risk
1 point = 1.3% risk
2 points = 4% risk
More than 2 points = 10% risk
Myocardial Infarction (MI)
Elective surgery should be deferred for 6 months after a myocardial infarct
Risk factors for postoperative myocardial re-infarction included the following:
i) Short time since previous infarct
ii) Residual major coronary vessel disease
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iii) Prolonged or major surgery
iv) Impaired myocardial function
Risk or postoperative re-infarction after a previous MI:
i) Within 0-3 months is 35%
ii) Within 3-6 months is 15%
iii) More than 6 months is 4%
60% of post operative myocardial infarcts are silent
The mortality of re-infarction is about 40%
Hypertension
In patients with hypertension there is need to assess degree of hypertension
and presence of end organ damage.
Risk of cardiovascular morbidity is increased in untreated or poorly controlled
hypertension.
Risk is present if diastolic pressure is greater than 95 mmHg.
Elective surgery should be cancelled if diastolic pressure is greater than 120
mmHg
(II). Respiratory disease

Respiratory diseases are associated with difficult airway, difficult mechanical
ventilation, chronic hypoxaemia, obstructive sleep apnoea, pulmonary
hypertension and postoperative hypoxaemia
Patients with lung disease are at increased risk of respiratory complications
such as bronchospasm, atelectasis, bronchopneumonia, hypoxaemia,
respiratory failure, pulmonary embolism.
In addition to routine preoperative investigations there is need to consider
chest radiography, spirometry, arterial blood gases.
Upper respiratory tract infections increase the risk of postoperative chest
complications. Elective surgery should be deferred for 2-4 weeks
Smoking doubles the risk of pulmonary complication and this persists for 3-4
months after stopping smoking.
Smoking increases blood carboxyhaemoglobi for at least 12 hours after last
cigarette
(III). Obesity
Morbidity and mortality after all surgery is increased in the obese patient.
Risk is increased even in the absence of other disease.
Body mass index (BMI) is the best measure of degree of obesity;
BMI = Weight in Kg / height in sqm
Normal BMI = 22-28
BMI greater than 28 means significant overweight
BMI greater than 35 is morbid obesity
Such patients are at risk of numerous complications and ICU bed may be
required postoperatively. Obesity may also be associated with gastro-
oesophageal reflux, abnormal liver function, insulin resistance and Type 2
diabetes, poor postoperative pain control and unpredictable pharmacological
responses.
14
(IV). Diabetes mellitus
Pre and perioperative management depends on severity of disease.
Diet controlled diabetes: No specific precautions.
Check blood sugar and consider Glucose-Potassium-Insulin (GKI) infusion if
>12 mmol/l.
Oral hypoglycaemics: Stop long acting sulphonylureas (e.g.
chlorpropamide) 48 hours prior to surgery. Short acting agents may be omited
on morning of operation.
Restart medication when the patient is eating normally.
Consider GKI infusion for major surgery.
Insulin dependent diabetes: Convert long acting insulins to 8-hourly Actrapid.
Place early on operating list. Give GKI infusion until eating normally.
GKI infusion:
15 u insulin
10 mmol potassium chloride
500 ml 10% dextrose
Infuse at a rate of 100 ml /hr.
(V). Obstructive Jaundice

Operative morbidity and mortality is increased in patients with obstructive
jaundice due to:
i) Coagulation disorders due to reduced absorption of fat soluble
vitamins (ADEK). Reversed with Fresh Frozen Plasma or Vitamin K
ii) Coagulation disorders due to reduced production of factors II, VII,
IX, X. Reversed with Fresh Frozen Plasma or Vitamin K
iii) Reduced wound healing
iv) Increased risk of infection
v) Hepato-renal syndrome. Acute renal failure in patient with jaundice.
Probably due to systemic endotoxaemia. Requires adequate
hydration and diuretics. Mannitol may help in management.
vi) Altered drug metabolism. Half life of many analgesics is prolonged.
(VI). Chronic renal failure

Chronic renal failure affects multiple organ systems leading to electrolyte
disturbances, impaired acid-base balance, anaemia, coagulopathy, impaired
autonomic regulation.
15
CHAPTER 3
METABOLIC RESPONSE TO TRAUMA
Similar responses are seen in trauma, burns, sepsis and surgery.

These involve both local and systemic reactions.
The extent of response is proportional to the severity of insult. The body
responds locally by inflammation and protective response to conserve fluid
and provide energy for repair. Resuscitation lowers the level of response.
There are two phases of this response;
a) the ebb phase in the first 24 hours characterized by reduced enzymatic
activity, reduced oxygen consumption, reduced cardiac output and a fall in
temperature (shock phase-lactic acidosis).
b). the flow phase. Has two stages
(i) the catabolic phase in the first 3-10 days associated with fat and
protein mobilization, increased urinary nitrogen excretion and weight
loss. This stage is associated with maintenance of the energy needs
of the body.
(ii) the anabolic stage is associated with replacement of lost tissue (fat
and protein) and weight gain. This occurs in the next 10-60 days.
An appropriate response maintains homeostasis and allows wound healing.
An excessive response can produce a systemic response such as the
systemic inflammatory response syndrome (SIRS) leading to multiple organs
dysfunction syndrome (MODS).
Initiation of response;
Several factors such as tissue injury, infection, hypovolaemia, hypoxia and
hypercarbia can initiate the physiological response to trauma.Multiple
simultaneous factors can have a synergistic effect.
Control of response;
Four factors control the response to trauma;
i) Sympathetic nervous system.
Due to hypothalamic activation of the sympathetic system
Has direct actions via the release of noradrenaline from
sympathetic nerves (neurotransmitters)
Has indirect action via the release of adrenaline from the adrenal
medulla. Produces cardiovascular, visceral and metabolic actions
This results in blood being diverted from skin and visceral organs,
Heart rate and myocardial contractility are increased
Bronchodilation occurs and gastrointestinal motility is reduced
Insulin production is reduced and glucagons production increased
Increased glycogenolysis increases blood sugar levels
ii) Acute phase response.
Tissue injury results in cytokine release. These are low molecular
weight proteins that include interleukin and interferons. They are
produced from activated leucocytes, fibroblasts and endothelial
cells as an early response to tissue injury and have a major role in
16
mediating immunity and inflammation. They act on surface
receptors on the target cells to influence protein synthesis within the
cell. This results in the production of acute phase proteins in the
liver (C-reactive protein, fibrinogen, alpha2 macroglobulin,
Complement C3 and other antiproteinases). These proteins act as
inflammatory mediators, antiproteinases and scavengers and act in
tissue repair.
Important cytokines include TNF-alpha, IL-1, IL-2, IL-6, interferon
and prostaglandins
Cytokines have mainly paracrine actions
They are important in regulating the inflammatory response. There
is reduced production of other proteins in the liver such as albumin
and transferrin. There is also reduced production of circulating
cations eg zinc and iron due to changes in production of transport
proteins.
Overflow of cytokines into systemic circulation is an important factor
in SIRS.
iii) Endocrine response (hypothalamic-pituitary-adrenal axis)
The hypothalamus, pituitary, adrenal axis is important via the
ascending reticular formation and limbic system effect on the
hypothalamus. This results in release of ACTH, GH and Prolactin
from Anterior pituitary and Arginine vasopressin (ADH) from
posterior pituitary.
Trauma increases ACTH and cortisol production
Steroids have a permissive action in many metabolic responses
Catabolic action increases protein breakdown. The following
systemic changes are observed as a result of the endocrine
response;
insulin antagonism increases blood sugar levels,
anti-inflammatory actions reduce vascular permeability,
aldosterone increases sodium reabsorption,
arginine vasopressin (ADH) increases water reabsorption and
produces vasoconstriction,
histamine increases vascular permeability,
total T4, total and free T3 levels are reduced.
iv) Vascular endothelium
Nitric oxide produces vasodilatation
Platelet activating factor augments the cytokine response
Prostaglandins produce vasodilatation and induce platelet
aggregation
Outcome of response;
The Endocrine response to surgery results in increased secretion of catabolic
hormones. This response was significant in evolutionary terms as a survival
mechanism to allow the injured animal to sustain themselves until injuries heal
by using stored body fuels, retaining salt and water to survive. This response
is not necessary in current surgical and anaesthetic practice.
(a) carbohydrate metabolism
17
Rise in blood glucose after surgery begins through increased levels of cortisol
and catecholamines, increased hepatic glycogenolysis and gluconeogenesis
and reduction in peripheral use of glucose.
The rise depends on intensity of surgical injury. The mechanisms of
maintaining glucose homeostasis are ineffective in the peri-operative period
because catabolic hormones promote glucose production, there is relative
lack of insulin and peripheral insulin resistance.
The risks of prolonged perioperative hyperglycaemia include increased
incidence of wound infection and impaired wound healing
(b) Protein metabolism
Increased cortisol causes protein catabolism. This leads to breakdown of
skeletal muscles and visceral muscles, and a rise in amino acid levels. The
amino acids are catabolised for energy or used in the liver to form new
proteins (acute phase proteins) or converted by liver to glucose, fatty acids or
ketone bodies.
This will lead to weight loss and muscle wasting after major surgery.
The effect can be measured by increased nitrogen excretion in urine.
It has been shown that patients on enteral nutrition supplemented with
arginine or glycine show faster recovery.
(c) Fat metabolism
During surgery there is increased lipolytic activity and fats stored as
triglycerides are converted to glycerol by cortisol, catecholamines and Growth
hormone. This activity can be inhibited by insulin. Glycerol is used as
substrate for gluconeogenesis in the liver. Fatty acids enter a pool and may
be oxidised in liver and muscle, converted to ketone bodies or re-esterified
(d) Water and Electrolyte metabolism
Arginine Vasopressin released from posterior pituitary causes water retention
and production of concentrated urine by direct action on kidney. Increased
secretion of hormone may continue for 3-5 days depending on severity of
surgical injury and the development of complications.
Renin is secreted by juxtaglomerular cells of the kidney as a result of
increased sympathetic efferent activation. This stimulates the production of
Angiotensin II causing release of aldosterone from adrenal cortex; causes
sodium and water reabsorption from distal tubules in the kidney.
(e) Inflammatory response
Inflammatory response produces clinically apparent local and systemic effects
The local response is usually the cardinal signs of inflammation
summary;
The outcome of systemic response includes:
Increased ECF volume and hypovolaemia
Increased vascular permeability and oedema
Early reduced urine output and increased urine osmolality
Reduced free water clearance
Late diuresis and increased sodium loss
Pyrexia in the absence of infection
Early reduction in metabolic rate
Late increased metabolism, negative nitrogen balance and weight loss
18
Lipolysis and ketosis
Gluconeogenesis via amino acid breakdown
Reduced serum albumin
Hyponatraemia due to impaired sodium pump action
Acid-base disturbance usually a metabolic alkalosis or acidosis
Immunosuppression
Hypoxia
Coagulopathy
Limitation of response;
inflammatory response can be limited by;
Reducing degree of trauma with appropriate and careful surgery
Reducing infection with wound care and antibiotics
Maintaining enteral nutrition
Controlling pain
Correcting hypovolaemia
Correcting acid-base disturbance
Correcting hypoxia
19
CHAPTER 4
SURGICAL NUTRITION
The body is composed of a fat and a lean (fat-free) body mass component.
Lean mass; the body's protein is contained in lean body mass, mostly as
skeletal muscle. Lean body mass is 50% to 60% muscle mass by weight and
the rest is bone and tendon. Protein makes up the critical cell structure in
muscle, viscera, red cells, and connective tissue. Enzymes that direct
metabolism and antibodies that maintain immune functions are also proteins.
It is the loss of body protein, not fat loss that produces the complications of
malnutrition; protein synthesis is essential for any tissue repair. Skin is
composed primarily of the protein collagen.
Table 10. Distribution of Fat and Lean Mass
Fat Mass (25%) Lean Mass (75%)

Energy store 70% Water
Metabolically inactive 20% Protein (Muscle 60%, Visceral 20%,
Connective tissue 15%, Essential proteins 5%.)
Contracts if energy demand exceeds intake 10% Mineral
Expands if energy intake in excess Essential for survival. Size regulated
Total stored; 150,000 kcal Capacity; 40,000 kcal
Fat mass; stored body fat is used primarily as a reservoir for energy. The size
of the fat depot is controlled by both genetic and environmental stimuli, such
as diet. Excess nutrients, especially carbohydrates, will expand the depot,
while inadequate intake will decrease depot size. There are 5 types of lipids;
free fatty acids (fat), Phospholipids, Lecithin, Cholesterol and Lipoproteins.
Fat undergoes conversion to fatty acids for energy use and re-conversion to
fat for storage (storage fat). A component of the essential lipids is used for all
membrane phospholipid content. Cholesterol is the lipid used for many
hormones and other essential molecules (essential fat). There are other
essential lipids used in normal metabolic activity, but they make up only a very
small proportion of the total fat mass.
Factors involved in the maintenance of lean body mass:
1. Genetic drive. Body composition is genetically determined especially the
lean mass component. There are a number of genetic adaptations the body
makes to maintain normal lean body mass or body protein, as any net loss of
body protein or lean mass is deleterious.
2. Anabolic hormones. Endogenous levels of anabolic hormones, human
growth hormone (HGH), testosterone, and, to some degree, insulin are
maintained at a level sufficient to increase net anabolism when needed to
maintain body protein content. This process is most evident during periods of
decreased intake where efficiency of protein synthesis increases and any
protein used for fuel is decreased to avoid a net loss. (This process is
overridden with the stress or fright-flight response).
3. Resistance exercise. Resistance exercise, which is muscle activity against
20
a force (eg, lifting objects, weight-bearing activity, a weight-lifting program),
leads to an anabolic stimulus that increases the protein synthesis of muscle.
4. Protein intake. Protein intake must be sufficient to allow for the necessary
new protein synthesis. The recommended daily allowance (RDA) is 0.8 g/kg
body weight/day. This amount increases with age, body stress, and wounds
when more protein synthesis is needed.
Table 11. Terminology of Nutrition
Term Definition
Energy The capacity to do work
Energy production Defined in terms of standard energy units produced per time
Energy Energy used/time ( eg, kcal/hour or mL oxygen/minute)
consumption
Kilocalorie (kcal) Standard measure of the quantity of energy obtained from nutrients (often referred to as a
calorie)
Metabolism Sum (body) total of all chemical reactions required for cell function, an energy-requiring
process
Hypermetabolism Increase in metabolic rate above normal
Anabolism Constructive metabolism or new tissue formation with protein synthesis
Catabolism Destructive metabolism or tissue degradation with protein breakdown
Common Causes of Weight Loss

There are 2 routes to involuntary weight loss.
(1)The first is via the acute injury or disease process, where increased
nutrient requirements and wasting of body protein are characteristic. The
presence of other stressors, such as pain and anxiety, can lead to the same
end point. Then, protein energy malnutrition (PEM) occurs rapidly, due to the
lack of any adaptive or protective responses. Often the insult or "stress"
resolves, but the weight loss and PEM are never corrected in the recovery
phase. With the presence of any catabolic insult, the degree of PEM exceeds
the degree of weight loss, as lean mass is not protected. Increased nutrient
losses due to gastrointestinal disease can lead to the same end point. The
stress response seen in illness, injury or infection leads to marked increase in
catecholamines and other stress hormones with a resultant hypermetabolic-
catabolic state. This increase in energy demands is provided by fat (50%),
carbohydrates (30%) and protein (20%). The increased use of protein for fuel
rapidly depletes lean body mass.
(2) The second route is due to inadequate nutrient intake, in both quality and
quantity. This process is very common in the elderly, those with disabilities,
those with lack of appetite from chronic illness, those with mental illness, and
those with poverty. The onset of severe weight loss precedes the PEM as
some adaptation will occur and lean mass is initially spared, but, eventually,
PEM will occur.
Whatever the route, the most common cause of weight loss and PEM is the
combination of increased nutrient demands and decreased intake.
Conditions Associated With development of malnutrition:
i). Catabolic illness, "the stress response" (eg, trauma, surgery, wounds,
infection, and corticosteroids)
21
ii). Involuntary weight loss exceeding 10% of ideal, for any reason
iii). Chronic illnesses (eg, diabetes, cancer, mental impairment, arthritis, and
renal failure)
iv). Increased nutritional losses; open wounds, enteral fistulas
v). Intestinal tract diseases impairing absorption
Malnutrition causes:
i. Delayed wound healing
ii. Reduced ventilatory capacity
iii. Reduced immunity and increased risk of infection.
However, it is not yet fully established that improving nutritional status
influences surgical outcome.
Methods of Measuring Body Composition:
Only body composition evaluations will determine how much of the weight
loss is lean body mass. The complications (e.g., weakness seen in the
patient), are often the best markers and should raise concern. But the extent
of body composition changes due to an insult or poor nutrition (or both) is not
easily determined after an injury. Restoration of body composition can be
more precisely defined, and the amount of weight that is lean mass and the
amount that is fat can be more accurately measured using currently available
techniques. If lean mass loss is the major problem, the anticipated weight
gained should be mainly lean mass.
There are a variety of methods to measure and monitor body composition
changes. The easiest (but least accurate) are anthropometric measurements.
These measurements can determine the progression or correction of
involuntary weight loss and PEM. However, the key value is the starting point
in the once-healthy state. An initial measurement, once PEM is present, will
assist with trends, but restoration of normal is the goal. The usual approach is
to measure either lean mass or fat mass and subtract that from total mass to
obtain the final composition.
1. Body mass index. The measurement of body mass index (BMI) determines
the body mass according to the relationship of weight to height and compares
it to a normal range.
The formula for BMI is weight in kilograms divided by height in square meters
(kg/m2). An estimate of fat mass is made, which can then be used to calculate
lean mass. Accuracy depends on how close the individual is to the "normal"
population. The BMI of a muscular individual (who maybe outside the norm)
would underestimate lean mass. A very obese individual would have a BMI
that overestimates lean body mass.
2. Skinfold thickness. This measurement estimates fat mass based on the
thickness of a skin fold at a number of precisely defined areas on the body.
The values are then used in a formula that includes other variables, such as
age. The value of contained fat assumes a homogenous fat distribution. Fat
mass is calculated and lean mass is derived by subtracting the fat mass from
the total mass.
3. Circumference measurements. Circumference measurements are taken for
specific body areas (waist to hip circumference ratio, mid-upper arm
circumference, forearm circumference, calf circumference) and then added to
22
the skinfold measure. Again the assumption is that the fat and muscle mass in
these areas can be compared with the reference population from which the
standard table is derived. The percentage of fat equals the circumference of
the right upper arm and abdomen minus the right forearm (in centimeters)
minus 10.2.
4. Bioelectric impedance analysis.
Bioelectric impedance analysis (BIA) measures body composition based on
the principle that lean mass has a higher electrical conductivity and lower
impedence relative to water, based on electrolyte content. BIA is an easy
bedside method; electrodes are attached to the extremities and a small
electrical current is used to obtain electrical and resistance measurements,
which can be converted to lean mass and fat mass measurements. This
method is the most common technique used to monitor body composition in
compromised patients. However, hydration must be adequate because the
measurement of lean body mass is really the measurement of body water, as
fat is water-free. Lean body mass is underestimated in a dehydrated patient
and, conversely, overestimated in an edematous patient.
Correction of Weight Loss (Protein Energy Malnutrition-PEM):
Correcting weight loss is multifactorial and requires a greater length of time to
reverse than to develop.
objectives to restoring lost lean mass are to:
1. eliminate the catabolic state
2. restore sufficient nutrient intake to meet current energy and protein needs
(calorie intake up to a 100% increase; protein intake 1.5 g/kg/day to 2
g/kg/day)
3. increase energy or calorie intake to about 50% above daily needs to begin
the process of weight and lean mass gain during recovery
4. increase protein intake to two times the RDA (recommended daily
allowance; from 0.8 g/kg/day to 1.5 g/kg/day) to allow for restoration of lost
lean mass during recovery
5. increase anabolic stimulation (which is abnormally low with PEM) to direct
the substrate from protein intake into protein synthesis (and restore normal
nutrient partitioning)
6. avoid replacement of lost lean mass with fat gain
7. use exercise (mainly resistance exercise) to increase the bodies' anabolic
drive to more rapidly regain lean mass
8. consider use of exogenous anabolic hormones to increase net protein
synthesis
To accomplish these objectives, a needs assessment must be completed.
This process can be divided into several components:
i) Energy or caloric requirements
ii) Protein requirements
iii) Nutrient mix
iv)Micronutrient requirements
i) Energy Expenditure
Energy expenditures can be calculated or directly measured. Calculation is
usually the preferred approach for the outpatient or the patient in a
23
rehabilitation center as the requirement for direct measurement is often
available only in an acute care facility. The first step in calculating energy
expenditure is to determine the basal metabolic rate (BMR) using predictive
equations.
The BMR is the amount of energy needed to maintain all functions while at
rest. It is measured shortly after awakening and in a fasting state for 12-18
hours.
The BMR depends on age, sex, and body size and correlates roughly with
body surface area. It is proportional to lean body mass, not to fat.
Resting energy expenditure, which is often used synonymously with BMR,
represents the amount of energy expended 2 hours after a meal under
conditions of rest and thermal neutrality. It is generally 10% higher than the
BMR.
The second step is to adjust BMR for any stress from injury, wounds, or
disease. As previously mentioned, metabolic rate (energy demands)
increases 20% after elective surgery and 100% after a severe burn. A wound,
infection, or traumatic injury will fall between these 2 extremes.
One simple formula for defining the stress factor is that described below. The
stress factor is the multiplier used in the BMR equation (Table 12).
Table 12. Stress Factors Relative to Insult
Stress Stress Factors

Minor surgery 1.2
Clean wound 1.2
Infected wound 1.3
Major trauma 1.5
Major sepsis 1.5
BMR needs to be adjusted in the recovery phase as part of the weight

restoration program and requires a 50% increase in energy (along with an
exercise program).
The last component to energy expenditure evaluation is to determine the
physical activity level of the patient.
Physical activity is adjusted by multiplying by the appropriate activity factor;
for patients confined to bed, it is 1.2, and for patients out of bed, it is 1.3. For
patients in an active resistance and endurance exercise program, the physical
activity factor is between 1.4 and 1.5.
Energy is required both for exercise and also to synthesize protein.
Thus, the energy requirements can be calculated as:
energy expenditure = BMR x stress factor x activity factor.
Usually, the basal or resting energy expenditure is about 25 kcal/kg ideal body
weight for the young adult and about 20 kcal/kg for the elderly. Requirements
for the injured or ill patient are usually 30% to 50% higher.
Protein-energy malnourished patients require a 50% increase over calculated
maintenance calories (energy) because they already have a protein deficit
and weight loss.
The reference standard for measuring energy expenditure in the clinical
24
setting is indirect calorimetry.
Indirect calorimetry is a technique that measures oxygen consumption and
carbon dioxide production to calculate resting energy expenditure and
respiratory quotient (RQ). One liter of oxygen consumed generates 3.9 kcal
(16.32 kJ); 1 liter of carbon dioxide produced generates 1.1 kcal (4.60 kJ).
Indirect calorimetry allows the precise measurement of the daily caloric
expenditure. Use of a stress factor to account for injury is not necessary
because the measured energy expenditure accounts for the effects of disease
state, stress, and trauma. However, because the measurement occurs at rest,
it is necessary to multiply by an "activity" factor of 1.0 to 1.3, depending on
whether the patient is intubated, at bed rest, or ambulatory. In addition,
indirect calorimetric data provide information on the use of carbohydrate, fat,
and protein oxidized for energy by monitoring the RQ. RQ is the ratio of
carbon dioxide expired to the amount of oxygen inspired (RQ = carbon dioxide
production/oxygen consumption). The RQ is used to develop the best
nutritional support regimen. Normal RQ ranges from 0.7-1.0. The nutrient mix
is adjusted to maintain an RQ of 0.8-0.85.
In clinical practice, basal energy expenditure (BEE) can be obtained from the
Harris-Benedict equation:
Males: BEE = 66.47 + 13.75 x W + 5.0 x H 6.76 x A
Females: BEE = 65.51 + 9.56 x W + 1.85 x H 4.68 x A
Infants: BEE = 22.1 + 31.05 x W + 1.16 x H
(W=weight, H=height, A=age)
ii) Protein requirement.
After determining calorie (energy) requirements, protein requirements are
assessed (Table 13). A healthy adult requires about 0.8 g protein/kg/day or
about 60 g to 70 g protein to maintain homeostasis. Nutritionally depleted,
nonstressed patients require at least 1.5 g/kg/day to restore body protein.
Stressed patients need more in the range of 1.5 g to 2.0 g protein/kg/day. The
increased need stems from additional demands for protein synthesis and
further amino acid loss due to normal protein synthesis. Urinary nitrogen
losses occur after injury and illness and increase with stress. Because
nitrogen content is used as a marker for protein, the 2 terms are used
interchangeably; 6.25 g protein is equal to 1 g nitrogen. Nitrogen balance
studies, such as a 24-hour urinary urea nitrogen measurement, that compare
nitrogen intake with nitrogen excretion can be helpful in determining patient
needs. Stressed, depleted patients usually cannot metabolize more than 2
g/kg unless an anabolic agent is added that can override the catabolic
stimulus. It is recommended that at least 15% of calories be supplied as
protein in head injury patients. Formula available for calculating protein
consumed;
N (gm N) = 0.006 x BEE
25
Table 13. Protein Requirements
During stress 1.5 g/kg/day to 2 g/kg/day

With established PEM 1.5 g/kg/day
To replace lost weight 1.5 g/kg/day
Elderly (healthy) 1 g/kg/day to 1.2 g/kg/day
Young (healthy) 0.8 g/kg/day
iii). Providing Nutritional Support (nutrient mix):

Healthcare providers should provide optimal nutrition early and include:
Adequate energy and nutrient profile; 30 cal/kg/day to 35 cal/kg/day
Adequate protein; 1.5 g/kg/day to 2 g/kg/day
Necessary micronutrients
Adequate water intake
Use of anabolic agents, if needed, to increase the rate of anabolic activity
Provide exercise to muscles
Basic principles:
Optimal nutrition is essential to keep up with the increased calorie demands
and to decrease the rate of catabolism. The first goal is to provide for the
calorie and protein demands. The second goal is to provide the appropriate
nutrient mix. Nutrient mix is typically 50% to 60% carbohydrate, 25% fat, and
20% to 25% protein, with the rate of onset, osmolarity of solution, and rate of
progression being dependent on gastrointestinal tolerance. Excess
carbohydrates (CHO) are deleterious and lead to hyperglycemia and excess
fat, which acts as a substrate for immunosuppressive mediators. Protein
requirements are 2-3 times the recommended daily allowance (RDA), or
about 1.5 g/kg body weight per day. The increased protein intake will
decrease the net nitrogen losses by increasing the amino acid flow into the
protein synthesis channel. Micronutrients need to be increased to keep up
with the increased metabolism and quickly restore deficiencies. It is essential
to initiate nutritional support as soon as possible after a catabolic insult within
48 hours in the presence of mild to moderate PEM. A more gradual
restoration of optimal nutrition is necessary with evidence of severe PEM, to
avoid a refeeding syndrome. The sudden restoration of nutrient intake,
especially carbohydrates, in severe malnutrition will suddenly reactivate a
number of dormant metabolic pathways. Lack of key micronutrients,
especially thiamine and other B complexes, will allow glucose to go through
oxidative phosphorylation resulting in lactate (lactic acid). The sudden
availability of CHO will exceed downregulated cell demands, necessitating
energy for fat production and leading to a further energy deficit. In addition,
there will be a shift of the previously depleted electrolytes, potassium,
phosphorous, and magnesium, back into cells, resulting in potentially severe
hypokalemia, hypomagnesemia, and hypophosphatemia. These compounds
must be returned into the intratratracellular compartment.
Nutritionally depleted patients need cautious refeeding orally, enterally or
parenterally, with feeds supplemented in potassium, phosphate and thiamine.
Generally, and particularly if oedema is present, these feeds should be
reduced in water and sodium. Though refeeding syndrome is a risk, improved
26
nutrition will help to restore normal partitioning of sodium, potassium and
water between intra and extra-cellular spaces
Surgical patients should be nutritionally screened, and NICE guidelines for
perioperative nutritional support adhered to. Care should be taken to mitigate
risks of the refeeding syndrome; a more gradual restoration of optimal
nutrition is necessary with evidence of severe protein energy malnutrition, to
avoid a refeeding syndrome. The most beneficial route for nutritional support
is the enteral (oral) route, which is really the only option for outpatients or
chronic care patients. If prior malnutrition has resulted in intestinal mucosal
atrophy and malabsorption is present, supplemental glutamine, 10 g to 20 g
per day, can be provided along with an elemental diet or protein hydrolysate,
until mucosal function improves. Oral intake of food is rarely sufficient to meet
either energy or protein needs in a catabolic or malnourished patient;
therefore, nutritional supplements are invariably needed.
Using a small nasogastric feeding tube is the first line of defence when severe
weight loss or PEM is detected, and it is used until the catabolic insult is
resolved and the patient is capable of taking adequate oral nutrition. It is most
often used in the acute or chronic care setting. Nutrient mix is typically 55% to
65% carbohydrate, 25% fat, and 20% protein. The solutions are isosmolar or
hyperosmolar, depending on the nutrient density. Hyperosmolarity is less well
tolerated, often leading to diarrhea. The increased fat content of most high-
energy supplements can also lead to impaired gastric emptying, necessitating
placement of a nasogastric tube. The increased carbohydrate content can
lead to hyperglycemia in the elderly or the diabetic population. There are
many tube feeding solutions available with nutrient mixes to meet a number of
different clinical disease states. In general, most are somewhat hyperosmolar
and free water is added. The parenteral (intravenous) route is used in the
acutely ill or injured hospital patient with catabolic disease.
iv). Micronutrient support.
Micronutrients are compounds found in small quantities in all tissues. They
are essential for cellular function and, therefore, for survival. It is becoming
increasingly clear that marked deficiencies in key micronutrients occur during
the severe stress response as a result of increased losses, increased
consumption during metabolism, and inadequate replacement. Because
micronutrients are essential for cellular function, a deficiency state further
amplifies stress, metabolic derangements, and ongoing catabolism or PEM.
The micronutrients include organic compounds (vitamins), and inorganic
compounds (trace minerals). These compounds are both used and excreted
at a more rapid rate after injury, leading to deficiencies. However, because it
is difficult to measure these micronutrients, prevention of a deficiency is
accomplished only by providing increased intake. Deficiency states can lead
to severe morbidity because adequate amounts of these key components are
essential for minimizing complications (table 7)
27
Table 14. Micronutrients
ORGANIC COMPOUNDS FUNCTION

1. Fat Soluble Vitamins
Vitamin A (Retinol) Synthesis of rhodopsin, epithelial cell and bone growth, inflammatory
stimulant, wound healing
Vitamin E Antioxidant in cell membranes
Vitamin D Regulation of calcium metabolism
Vitamin K Activates blood clotting factors II, VII, IX, X
2. Water Soluble Vitamins
Thiamine (Vit B1) Oxidative decarboxylation
Riboflavin (Vit B2) Electron transfer during oxidative phosphorylation
Niacin (Vit B3) Nicotinamide-adenide Dinucleotide electron transfer reactions
Pantothenic acid Part of coenzyme A
Biotin Carbon dioxide transfer reactions
Pyridoxine (Vit B6) Transamination and decarboxylation reactions
Folic acid One carbon transfer reaction
Vitamin B12 (cobalamin) Production of methionine coenzyme A reactions
Ascorbic acid (Vit C) Antioxidant in cytosol collagen synthesis, Carnitine production
INORGANIC COMPOUNDS (Trace
Minerals)
Chromium Use of glucose and insulin. Potentiates insulin action
Cobalt Required for vitamin B12 synthesis
Copper Connective tissue development through collagen cross linking
Iodine Thyroid hormones
Iron For haemoglobin and oxygen transport, electron transfer in oxidative
phosphorylation
Manganese Procollagen ground substance formation, brain function, neuromuscular
function, fatty acid synthesis
Molybdenum Metabolism of purines, pyramidines, redox reactions
Selenium Antioxidant and fat metabolism
Although the doses of micronutrients required to correct PEM are not well
defined, a dose 5-10 times the RDA is usually suggested until the PEM is
corrected.
Hydration.
Water is an essential nutrient. It is required to transport nutrients and remove
by-products from cell metabolism as well as to maintain cardiovascular
stability. Dehydration is a major problem in patients with the "stress response"
due to increased evaporative losses and established PEM due to both lack of
intake and increased losses. This is especially true in the elderly because
aging kidneys are not able to concentrate urine efficiently. These problems,
combined with a decreased thirst sensation, result in inadequate hydration. In
addition, more water is needed to process and excrete the necessary
increased calorie and protein intake. Causes of
Dehydration; reduced thirst sensation, reduced intake throughout the day,
increased kidney loss due to aging, lack of replacement after increased
gastrointestinal losses. Losses due to medications, especially diuretics.
Recommendations of daily fluid intake are based on caloric intake as well as
replacement of losses. Optimal macronutrient intake in the absence of
inadequate fluid will lead to poor nutrient processing and can accentuate the
28
degree of dehydration.
The recommendations for daily fluid intake are as follows:
i. 30 mL to 35 mL per kg body weight
ii. minimum of 1500 mL/day
iii. 1 mL to 1.5 mL per calorie consumed
iv. replacement of added losses from disease or medications
Nutrient supplements.
Numerous studies demonstrate the need for increased protein intake during
both the catabolic and recovery phase after injury. The increased protein
demands, especially if restoration of depleted body lean mass is required,
often exceed that which a severe wound patient can achieve with oral intake
alone. This concept is well documented in the management of the burn wound
patient; the addition of protein supplements to maintain intake at 1.5 g/kg to
2.0 g/kg per day significantly increased the healing rates.
As described, the protein intake correlates best with correction of PEM and
wound healing rate. Nutrient supplements should be selected based on the
following criteria:
i. Sufficient protein content
ii. Sufficient caloric content
iii. Quality of the contained nutrients
iv. Route of administration (ie, taken orally or tube feeding)
v. Palatability
Many high-protein supplements are nonpalatable and not for oral
consumption; they are used specifically for tube feeding. However, palatable,
oral high-protein formulations are now available.
Nutritional support in surgery:
Literature suggests that early parenteral nutrition does not improve clinical
outcomes except in severely malnourished patients where nutritional support
is provided for at least seven days pre-operatively.
High dose parenteral glutamine may reduce infectious complications and the
length of hospitalisation for surgical patients.
Guidelines from American Society for Parenteral and Enteral Nutrition
(ASPEN); Nutritional support should be initiated for patients unable to take
adequate oral nutrition for 7-14 days.
Guidelines:
Identify early which patients may benefit from parenteral nutrition or enteral
nutrition.
Provide optimal combination of nutrients
Closely monitor patients progress through out the course of therapy.
Advantages of enteral nutrition over parenteral nutrition:
Preferred route of nutritional support
Enteral tube feeding promotes maintenance of gastrointestinal mucosal
integrity through regular delivery of nutrients into the gastrointestinal tract.
This reduces risk of mucosal atrophy, infectious complications, multiorgan
failure and death.
More physiological, safe and less expensive.
29
Nutritional Assessment:
i). History; weight loss, dietary habits, dentition, absorption, appetite.
Physical examination; signs of muscle and fat wasting, poor wound healing,
poor skin integrity.
Body weight and weight history: compare weight with ideal body weight for
height. Compare current body weight with usual body weight (loss of 10%
last 6 months or 5% last one month significant. Associated with significant
increases in morbidity and mortality).
ii). Body Mass Index: Can be used to asses nutritional status; weight in kg/
height in sq, metres. Body mass index of less than 15 Kg/sq m has been
associated with significant increase in morbidity and mortality.
iii). Plasma proteins: (i) albumin; Synthesized and catabolised in the liver. Has
long half life (20 days). Normal levels=3.5-5g/dL. Reduced levels in acute
injury and illness due to reduced synthesis by liver and increased production
of acute phase reactant proteins. Levels are low in hepatic failure. There is
increased renal loss of albumin with low serum levels in nephrotic syndrome
and enteropathies. Systemic inflammation results in reduced albumin
synthesis, increased degradation and transcapillary leakage of albumin.
Serum albumin levels are low in fluid overload and high in dehydration.
Albumin levels are excellent predictor of surgical outcomes because low
preoperative levels are associated with poor nutrition or advanced disease.
(ii). Prealbumin (transthyretin). Transport protein for thyroid hormone.
Synthesized by the liver and partly catabolised by the kidneys. Has short half
life (2-3 days) therefore more favourable marker of acute change in nutritional
status. Test expensive therefore not routinely done. Normal levels=16-40
mg/dL. Levels below 16 mg/dL area associated with malnutrion. High levels
are seen in renal dysfunction, corticosteroid therapy and dehydration. Low
levels are seen in physiological stress, infection, liver dysfunction, and over-
hydration. (iii) Acute phase reactants e.g. C-reactive protein. May increase
thousand fold in inflammation, infection and physiological stress. Transferrin;
transport protein for iron. Half life of 8-10 days. Normal levels=200-360
mg/dL. Reduced levels in malnutrition. Expensive to measure.
iv). Subjective Global Assessment (SGA). Information on weight change,
dietary history and physical examination enables patients to be classified as
well nourished, moderately malnourished and severely malnourished. SGA
can predict post-operative nutrition related complications. The results are
reproducible and can therefore be used for nutritional assessment of surgical
patients.
Nutritional Support.
The disease process should be considered when discussing nutritional
options for a specific patient. Patients wishes, prognosis, severity of illness,
anticipated duration of inadequate oral intake, risks associated with nutritional
support access and infusion and potential effects of not providing infusion are
some of the factors that may need to be addressed.
It is important to avoid aggressive overfeeding as well as prolonged
underfeeding. Aggressive overfeeding is associated with
hypertriglyceridaemia, hepatic steatosis and hypercapnia. This may lead to
30
prolonged dependence on mechanical ventilation. Prolonged underfeeding is
associated with a compromised immune function, delayed wound healing,
may exacerbate muscle wasting and may lead to prolonged recovery of
nitrogen balance and visceral protein levels.
Caloric requirements may be measured by indirect calorimetry; Expensive
therefore not routinely available. Translates gas exchange across the lungs
into patients daily energy requirements.
Pre-operative nutritional status of the patient.
The underlying pathophysiologic condition prompting surgery.
Stress factors from the surgical procedure (minor or major).
ASPEN guidelines; caloric needs for catabolic patients fall between 25-30
total kcal/kg/day. Allowance may be made for acute phase response.
Protein
Protein plays an important role in tissue maintenance, wound healing, and
protein supplements slow down endogenous protein catabolism after major
surgery.
Postoperative protein requirements range between 1.2-2g/kg and may be
lower in uncomplicated elective surgery and higher in major surgery. Protein
requirements a lower in severe hepatic and renal dysfunction and high in
severe open wounds and burns (>2g/kg).
Carbohydrate versus lipids.
Carbohydrates are important protein-sparing fuel source for glucose
dependent tissues such as bone marrow, erythrocytes and brain tissue. 100-
150g of carbohydrates per day suppress gluconeogenesis and prevents
ketosis. Provide 70-85% of non-protein calories.
Intravenous lipids may act as alternate source of non-protein calories.
Reduces hepatic complications associated with parenteral nutrition. Reduces
carbon dioxide production and improve glycaemic control. Provide essential
long chain fatty acids, linoleic acids, and alpha linoleic. 1-2% of calories
should be given in this form as 500 mL of 20% lipids once a week at
maximum infusion rate of 2.5g/kg/day upto 1g/kg/day in the critically ill to
prevent the production of immunosuppresive , proinflammatory eicosanoids.
Immunonutrition:
This is controversial.
glutamine. Its a non-essential amino acid synthesised by almost all body
tissue. Acts as nitrogen courier among organs, a source of fuel for
lymphocytes, hepatocytes, and the intestinal mucosa and as substrate for
gluconeogenesis and protein synthesis.
Low levels seen catabolic stress may be associated with immune dysfunction
and increased hospital mortality. However, supplementation is controversial
because glutamine can be degraded to ammonia and cause hepatic
encephalopathy. Studies show daily doses of 0.2-0.5 g/kg to be safe and
beneficial in surgical and critically ill patients.
arginine. Nonessential amino acid but becomes essential under conditions of
metabolic stress. Associated with improved nitrogen balance and wound
healing due to its nitrogen level. It is immunoenhancing through promotion of
macrophage and natural killer tumour cytotoxicity and T-cell proliferation and
31
activation. Its a precursor to nitric oxide which is involved in regulation of
vascular tone and immune function. Its used in combination as a component
of immune enhancing enteral formular containing Omega-3 fatty acids and
nucleotides.
Omega-3 fatty acids. Derived from fish oils. Compete with fatty acids for
incorporation into the cell membrane. Give rise to anti inflammatory and
antithrombotic eicosanoids.
Nucleotides. Structural units of DNA and RNA. Thought to have potential
immunoenhancing effects with regard to natural killer cells and T
lymphocytes.
Immunonutrition may improve outcome in elective surgical patients but
probably harmful in critically ill patients due to excess nitric oxide production
which may cause abnormal haemodynamic status and immune function in the
critically ill who already have an enhanced immune response unlike general
surgery patients who may have post-operative immunosuppression.
Recommendations on immune enhancing enteral therapy;
May be indicated in moderately severly malnourished patients undergoing
major elective upper-GIT surgery (albumin concentration<3.5 g/dL) and
severely malnourished patients undergoing lower-GIT surgery ( albumin
concentration <2.8g/dL). Should not be used where patients are expected to
resume adequate oral intake within five days, patients with bowel obstruction
distal to the access site, patients with incomplete resuscitation or splanchnic
hypoperfusion and in patients with major GIT haemorrhage caused by varices
or peptic ulcer disease with a visible vessel on endoscopy.
Should be started 5-7 days pre-operatively at 50-60% of estimated nutrient
needs and given for minimum five days post surgery. Benefits include
reduction in infectious complications, length of stay and resource utilisation
(i.e. hospital inputs and therefore reduced costs).
Monitoring of nutritional support adequacy:
Clinical monitoring. Weight. Fluid balance. Wound healing.
Biochemical. Albumin, pre-albumin, transferrin.Nitrogen balance.
Assess nitrogen intake versus nitrogen loss.
Nitrogen intake = protein delivered in gms/6.25.
Nitrogen loss = urea nitrogen from a 24 hour urine collection + 3-5g of
insensible nitrogen losses.
The goal is to achieve a positive nitrogen balance in nutritional support. This
may be difficult to achieve in the acute phase of critical illness, or heavy
protein losses e.g. drainage from large wounds, protein losing enteropathy
and renal dysfunction.
Principles of surgical nutrition :
Clinical assessment.
Weight loss (10% =mild malnutrition, 30% = severe malnutrition).
Body mass index
Anthropometric assessment; Triceps skin fold thickness, Mid arm
circumference, Hand grip strength
Blood indices: Reduced serum albumin, prealbumin or transferrin,
Lymphocyte count.
32
However, no index of nutritional assessment has been shown to be superior
to clinical assessment.
Methods of nutritional support:
Use gastrointestinal tract if available
prolonged post-operative starvation is probably not required. Early enteral
nutrition reduces post-operative morbidity.
Enteral feeding:
Prevents intestinal mucosal atrophy Supports gut associated immunological
shield, attenuates hypermetabolic response to injury and surgery Cheaper
than TPN and has fewer complications
Polymeric liquid diet: Short peptides, medium chain triglycerides and
polysaccharides Vitamins and trace elements
Elemental diet; L-amino acids, simple sugars, expensive and unpalatable,
high osmolarity can cause diarrhoea, Enteral feed can be taken orally or by
nasogastric tube, Nasoenteral tube - usually fine bore.
Long term feeding can be by:
Surgical gastrostomy, jejunostomy, Percutaneous endoscopic gastrostomy,
Needle catheter jejunostomy
Rate of infusion often started at low rate and increased.
Strength of initial feed often diluted and strength gradually increased.
Complications of enteral feeding;
Malposition and blockage of tube, Gastrooesophageal reflux. Feed
intolerance
Isotonic solutions should be used at full strength starting at 30 ml/hr. Check
gastric residuals every 4 hours and withhold feeding if residual exceeds 125ml
in an adult. Rate may be increased 15-25ml/hr every 12-24 hours until
optimum rate is achieved.
Parenteral nutrition;
Intestinal failure = A reduction in functioning gut mass below the minimal
necessary for adequate digestion and absorption of nutrients. Useful concept
for assessing need for total parenteral nutrition (TPN). Can be given by either
a peripheral or central line
Indications for total parenteral nutrition;
Absolute indications; Enterocutaneous fistulae
Relative indications; Moderate or severe malnutrition, Acute pancreatitis,
Abdominal sepsis, Prolonged ileus, Major trauma and burns, Severe
inflammatory bowel disease.
Peripheral parenteral nutrition; Hyperosmotic solution, Significant problem
with thrombophlebitis, Need to change cannulas every 24- 48 hours, No
evidence to support it as a clinically important therapy, Composition - 12g
nitrogen, 2000 Calories.
Central parenteral nutrition; Hyperosmolar, low pH and irritant to vessel walls,
Typical feed contains the following in 2.5L; 14g nitrogen as L amino acids,
250g glucose, 500 ml 20% lipid emulsion, 100 mmol Na+ , 100 mmol K+, 150
mmol Cl- , 15 mmol Mg2+ , 13 mmol Ca2+ , 30 mmol PO42- , 0.4 mmol Zn2+ , Water
and fat soluble vitamins, Trace elements
Complications of subclavian and jugular central venous lines; 10% of central
33
lines develop significant complications. Problems of insertion; (Failure to
cannulate, Pneumothorax, Haemothorax, Arterial puncture, Brachial plexus
injury, Mediastinal haematoma, Thoracic duct injury). Problems of care; (Line
and systemic sepsis, Air embolus, Thrombosis, Catheter breakage)
Monitoring of parenteral nutrition:
Feeding lines should only be used for that purpose. Drugs and blood products
should be given via separate peripheral line. 5% patients on TPN develop
metabolic derangement.
Nutrition should be monitored: Clinically - Weight, Biochemically-twice weekly,
FBC, U+Es, LFTs, Mg2+, Ca2+, PO42-, Zn2+ , Nitrogen balance, Blood cultures
on any sign of sepsis.
Metabolic complications of parenteral nutrition; hyponatraemia, hypokalaemia,
hyperchloraemia, trace element and folate deficiency, deranged LFTs, linoleic
acid deficiency.
Nutrition in the head injured patient
Head injury patients have a metabolic expenditure 140% of normal. This is
reduced by paralysis with muscle blocker or barbiturate to 120%. Mortality is
reduced in patients who receive full caloric replacements by day 7 post-
trauma. To achieve this objective, begin nutritional replacement therapy within
72 hours of head injury.
Nutritional requirements: Basal energy expenditure; Harris-Benedict equation
Aim to achieve expectations by day 7.
Aim for between 100-140% of the basal energy expenditure depending on
whether is paralysed or nonparallysed.
15% of calories given as protein.
34
CHAPTER 5
FLUID AND ELECTROLYTE BALANCE IN SURGERY.
Daily requirements for the average 70 Kg man;

Total body water is 42 L (approximately 60% of body weight)
28 L is in the intracellular and 14 L in the extracellular compartments
The plasma volume is 3 L
The extravascular volume is 11 L
Total body sodium is 4200 mmol (50% in extracellular fluid-ECF)
Total body potassium is 3500 mmol (only about 50-60 mmol in ECF)
Normal osmolality of ECF is 280 295 mosmol/kg
Fluid replacement;
When calculating fluid replacement for a patient one needs to consider:
(i) Maintenance requirements
(a) Daily maintenance fluid requirements vary between individuals.
70 Kg male = 2.5 - 3.0L water, 120 140 mmol sodium and 70 mmol
potassium
40 Kg woman = 2.0L water, 70 90 mmol sodium and 40 mmol potassium
(b) Daily maintenance fluid requirements for children
0-10 kg; 100 ml/kg
10-20 kg; 1000 ml + 50 ml/kg for each kg above 10
>20 kg is 1500 ml + 25 ml/kg for each kg above 20
(ii) Replacement of losses. Two types;
(a) Pre-operative or pre-admission ongoing losses; nasogastric aspirate,
vomit, diarrhoea, stoma, drains, fistula etc
Most surgical ongoing losses are rich in sodium and should be replaced with
0.9% (Normal) saline
(b) Insensible losses; faeces approximately 100 ml/ day, lungs approximately
400 ml/ day, skin approximately 600 ml/ day
Types of Fluids
Table 15. Crystalloids
Hartmans Normal Dextrose Ringers 5% Extracellular

solution saline saline lactate Dextrose fluid
Sodium (mmol/l) 131 154 30 130 Nil 142
Chloride (mmol/l) 111 154 30 109 Nil 103
Potassium 5 Nil Nil 4 Nil 4
(mmol/l)
Bicarbonate 29* Nil Nil 28* Nil 27
(mmol/l)
Calcium (mmol/l) 2 Nil Nil 1.5 Nil 5
Lactate (mmol) 29 28
mOsm/L 279 308 560 273 252 280-295
(*present as lactate that is converted to bicarbonate)

Monodispersed = All molecules of similar molecular weight
Polydispersed = Molecules have spread of molecular weights
35
Table 16. Composition of colloids
Volume effect Average MW Circulatory half life

(%) (kDa)
Gelatins 80 35 2-3 hours
(Haemacel)
4% Albumin 100 69 15 days
Dextran 70 120 41 2-12 hours
6% Hydroxyethyl Starch 100 70 17 days
Albumin; Monodispersed. Expensive. Long half life

Accounts for 60-80% of normal plasma oncotic pressure
No adverse effect on coagulation
Dextrans. Polysaccharides; Polydispersed with MW 10-90 kDa
Reduces plasma viscosity. Reduces platelet aggregation. 1-5% develop
anaphylaxis
Gelatins. Polypeptides; Polydispersed with MW 35 kDa. Rapidly lost from
vascular space
Hydroxyethyl starch. Synthetic polysaccharide polymers derived from
amylopectin; Polydispersed with MW 50-450 kDa. Large molecules engulfed
by reticuloendothelial system. Associated with bleeding diathesis
Fluid management.
(a) Preoperative fluid management
In patients without disorders of gastric emptying undergoing elective surgery
clear non-particulate oral fluids should not be withheld for more than two
hours prior to the induction of anaesthesia.
In the absence of disorders of gastric emptying or diabetes, preoperative
administration of carbohydrate rich beverages 2-3 h before induction of
anaesthesia may improve patient well being and facilitate recovery from
surgery. It should be considered in the routine preoperative preparation for
elective surgery.
Routine use of preoperative mechanical bowel preparation is not beneficial
and may complicate intra and postoperative management of fluid and
electrolyte balance. Its use should therefore be avoided whenever possible.
Where mechanical bowel preparation is used, fluid and electrolyte
derangements commonly occur and should be corrected by simultaneous
intravenous fluid therapy with Hartmanns or Ringer-Lactate.
Excessive losses from gastric aspiration or vomiting should be treated
preoperatively with an appropriate crystalloid solution and potassium
supplement. Hypochloraemia is an indication for the use of 0.9% saline, with
sufficient additions of potassium and care not to produce sodium overload.
Losses from diarrhoea, ileostomy, small bowel fistula, ileus or obstruction
should be replaced volume for volume with Hartmanns or Ringer-Lactate
solutions. Saline depletion, for example due to excessive diuretic exposure,
is best managed with a balanced electrolyte solution such as Hartmann's.
36
In high risk surgical patients, preoperative treatment with intravenous fluid and
inotropes should be aimed at achieving predetermined goals for cardiac
output and oxygen delivery as this may improve survival.
Hypovolaemia can be diagnosed clinically on the basis of pulse, peripheral
perfusion and capillary refill, venous pressure and Glasgow Coma Scale
together with acid-base and lactate measurements. Hypovolaemia due to
blood loss should be treated with either a balanced crystalloid solution or a
suitable colloid until packed red cells are available. Hypovolaemia due to
severe inflammation such as infection, peritonitis, pancreatitis or burns should
be treated with either a suitable colloid or a balanced crystalloid. Critically ill
patients are at risk of developing interstiatial oedema during fluid replacement
because they are unable to excrete excess sodium adequately. The
administration of large volumes of colloid should be accompanied by sufficient
free water (e.g. 5% dextrose) to maintain normal serum osmolality.
(b) Intraoperative Fluid Management
Perioperative fluid management in brain surgery should aim at preserving
cerebral perfusion pressure (CPP), maintaining normovolaemia and ICP.
Cerebral capillary membranes, unlike systemic capillary membranes, are
impermeable to ions due to the blood brain barrier. Isotonic crystalloids such
as sodium chloride are preferred during intraoperative management. Fluid
replacement guidelines will vary for routine craniotomy, traumatic brain injury,
or when there is associated diabetes insipidus and subarachnoid
haemorrhage.
In major elective surgery, intraoperative treatment with intravenous fluid to
achieve an optimal value of stroke volume should be the aim where possible
as this may reduce postoperative complication rates and duration of hospital
stay.
In non-elective major surgery intravenous fluids should be given to achieve an
optimal value of stroke volume during and for the first eight hours after
surgery.
(c) Postoperative fluid management.
Record the amount and type of fluid given during surgery and compare with
fluid losses in theatre, insensible losses and urine output and determine the
volume status of the patient. If the patient is euvolaemic and
haemodynamically stable, oral fluid administration should be done as soon as
possible. If the patient needs intravenous maintenance fluids, low sodium
fluids should be used until sodium and fluid balance is stable after the
excretion of the perioperative sodium load. The routine daily maintenance
fluid requarement (with replacement of any additional losses) is then given.
In the presence of generalised oedema, any hypovolaemia should first be
corrected and then a negative sodium and water balance maintained, guided
by urine sodium concentration or excretion and maintenance of normal
plasma sodium and potassium levels.
(d) Fluid resuscitation in shock
Circulatory shock states and severe intravascular volume depletion from
diarrheah usually require large amounts of intravenous fluid replacement.
Intravascular volume deficiency is acutely compensated by vasoconstriction,
37
followed over hours by migration of fluid from the extravascular compartment
to the intravascular, maintaining circulating volume at the expense of total
body water. However, this compensation is overwhelmed after major losses.
Choice of resuscitation fluid depends on the cause of the deficit.
i. Hemorrhagic hypovolaemia
Loss of RBCs diminishes oxygen carrying capacity. However, the body
increases cardiac output to maintain oxygen delivery and also increases
oxygen extraction. These factors provide a safety margin of almost ten times
the resting oxygen requirement. Therefore crystalloid or colloid solutions may
be used to restore intravascular volume in mild to moderate blood loss.
However, once Hb declines to below 7 g/dL, in the absence of cardiac or
cerebral vascular disease, oxygen-carrying capacity must be restored by
infusion of blood. Patients with coronary or cerebral vascular disease require
blood for Hb below 10 g/dL.
Crystalloid solutions for intravascular volume replenishment are typically
isotonic (eg, 0.9% saline or Ringer's lactate). Water freely travels outside the
vasculature, so as little as 10% of isotonic fluid given remains in the
intravascular space. With hypotonic fluid (eg, 0.45% saline), even less
remains in the vasculature and thus is not used for resuscitation. Both 0.9%
saline and Ringers lactate are equally effective; Ringers lactate may be
preferred in hemorrhagic shock because it minimizes acidosis. However, the
Calcium in Ringers lactate may interfere with concurrently infused drugs and
may trigger clotting in transfused blood unless the ratio of blood to Ringers
lactate is more than 2 to1. For patients with acute brain injury and
hemorrhagic shock, 0.9% saline is preferred. Hypertonic saline (7.5%) is also
an effective crystalloid; it shifts more volume from the extravascular space
and therefore requires lower absolute volume, which has practical advantages
in a pre-hospital setting.
Colloid solutions (eg, hydroxyethyl starch, albumin, dextrans) are also
effective for volume replacement during major hemorrhage. Despite
theoretical benefits over crystalloid, no differences in survival have been
proven. Albumin is the colloid of choice, although it may have a negative
inotropic effect. Both dextrans and hydroxyethyl starch may adversely affect
coagulation when more than 1.5 L is given.
Blood typically is given as packed RBCs, which should be cross-matched, but
in an urgent situation, 1 to 2 units of type O Rh-negative blood are an
acceptable alternative. When more than 2 units are transfused (eg, in major
trauma), blood is warmed to 37 C. Patients receiving more than 8 units may
require replacement of clotting factors with fresh frozen plasma,
cryoprecipitate or platelets.
ii. Nonhemorrhagic hypovolemia
Isotonic crystalloid solutions are given during shock and hypovolemia. Colloid
solutions are generally not used. Patients with dehydration and adequate
circulatory volume typically have a free water deficit, and hypotonic solutions
(eg, 5% dextrose or 0.45% saline) are used.
Route and Rate of Fluid Administration
38
Standard, large (eg, 14- to 16-gauge) peripheral IV catheters are adequate for
most fluid resuscitation. With infusion pump 1 L of crystalloid in 10 to 15 min
and 1 unit of packed RBCs can be given in 20 minutes. For patients at risk of
exsanguination, a large central venous catheter provides more rapid infusion
rates; a pressure infusion device can infuse 1 unit of packed RBCs in less
than five minutes.
Adults are given 1 L of crystalloid (20 mL/kg in children) or, in hemorrhagic
shock, 5 to 10 mL/kg of colloid or packed RBCs, and the patient is
reassessed.
(e) End point and Monitoring
The actual end point of fluid therapy in shock is normalization of oxygen
delivery usually determined by clinical indicators of end-organ perfusion such
as urine output of more than 0.5 to 1 mL/kg/hour. Other clinical indicators
such as heart rate, mental status, and capillary refill may be unreliable
because they may be influenced by the underlying disease process. Because
of compensatory vasoconstriction, mean arterial pressure (MAP) is only a
rough guideline; organ hypoperfusion may be present despite apparently
normal values. An elevated arterial blood lactate level reflects hypoperfusion;
however, levels do not decline for several hours after successful resuscitation.
Urine output does not provide a minute-to-minute indication of the success of
resuscitation and measures of preload may be helpful in guiding fluid
resuscitation for critically ill patients. Central venous pressure (CVP) is the
mean pressure in the superior vena cava, reflecting right ventricular end-
diastolic pressure or preload. Normal CVP ranges from 2 to 7 mm Hg (3 to 9
cm H2O). A sick or injured patient with a CVP < 3 mm Hg is presumed to be
volume depleted and may be given fluids with relative safety. When the CVP
is within the normal range, volume depletion cannot be excluded, and the
response to 100- to 200-mL fluid boluses should be assessed; a modest
increase in CVP in response to fluid generally indicates hypovolemia. An
increase of > 3 to 5 mm Hg in response to a 100-mL fluid bolus suggests
limited cardiac reserve. A CVP > 12 to 15 mm Hg casts doubt on hypovolemia
as the sole etiology of hypoperfusion, and fluid administration risks fluid
overload.
A slightly different approach in determining the resuscitation end-point is
applied in patients with traumatic haemorrhagic shock. Experimental and
clinical evidence indicates that internal hemorrhage (eg, from visceral or
vascular laceration or crush) may be worsened by resuscitation to normal or
supranormal mean arterial pressure (MAP). A MAP of 60 to 80 mm Hg may
be used as the resuscitation end point in such patients pending surgical
control of bleeding.
After blood loss is controlled, Haematocrit (Hct) is used to guide the need for
further transfusion aiming at a target Hct of 23 to 28% and 30% for patients
with coronary or cerebral artery disease who may be unable to tolerate
moderate anaemia. Higher Hct levels do not improve outcome and have a
risk of increased blood viscosity and impaired perfusion of capillary beds.
Assessment of adequacy of resuscitation:
1. Clinical history and observations; Pulse, blood pressure, skin turgor
39
2. Urine output; oliguria < 0.5 ml/kg/hr
3. CVP or pulmonary capillary wedge pressure
4. Response of urine output or CVP to fluid challenge
A fluid challenge should be regarded as a 200-250 ml bolus of colloid
This should be administered as quickly as possible
A response in the CVP or urine output should be seen within minutes
The size and duration of the CVP response rather the actual values recorded
is more important.
Because of the risk of inducing hyperchloraemic acidosis in routine practice,
when crystalloid resuscitation or replacement is indicated, balanced salt
solutions (e.g. Ringers lactate/acetate or Hartmanns solution) should replace
0.9% saline, except in cases of hypochloraemia.
Solutions such as dextrose/saline and 5% dextrose are important sources of
free water for maintenance, but should be used with caution as excessive
amounts may cause dangerous hyponatraemia, especially in children and the
elderly. These solutions are not appropriate for resuscitation or replacement
therapy except in conditions of significant free water deficit (e.g. diabetes
insipidus).
To meet maintenance requirements, adult patients should receive sodium 50-
100 mmol/day, potassium 40-80 mmol/day in 1.5-2.5 litres of water by the
oral, enteral or parenteral route (or a combination of routes). Additional
amounts should only be given to correct deficit or continuing losses. Careful
monitoring should be undertaken using clinical examination and fluid balance
charts.
(f) Complications
i. Rapid infusion of fluids may precipitate pulmonary edema.
ii. Hemodilution may occur from crystalloid infusion. Hct must be
monitored.
iii. RBC transfusion has a low risk of directly transmitting infection but
in critically ill patients, it seems to cause a slightly higher rate of
hospital-acquired infection. This risk may be minimized by using
blood less than 12 days old; such RBCs are more plastic and less
likely to cause sludging in the microvasculature.
iv. Complications of massive transfusion.
Hyponatraemia:
causes
(a) Volume overload in extracellular fluid
(b) Cerebral salt wasting. Loss of sodium through urine with hypovolaemia in
intracranial diseases of unknown aetiology. Should be treated with normal
saline.
(c) post-operative hyponatraemia. Rare.
Symptoms
Gradual loss; anorexia, headache, irritability, muscle weakness.
Rapid loss (severe); neuromuscular excitability, cerebral oedema, muscle
twitching, cramps, nausea/vomiting, confusion, seizures,respitatory
arrest, coma, death.
40
Treatment: Fluid restriction in chronic asymptomatic cases.
In acute symptomatic patients risk of brain oedema, herniation and
cardiorespiratory arrest. Give 3% (513 mEq/l) or 5% (856 mEq/l) NaCl. 25-50
cc/hr. Avoid rapid correction of hyponatraemia; Results in osmotic
demyelination syndrome (cerebral pontine myelinolysis, demyelination of the
pons and other cerebral white mater). First described in alcoholics. Presents
as insidious flaccid quadriplegia, mental status changes, cranial nerve
abnormalities, pseudobulbar palsy.
Give simultaneously furosamide to prevent volume overload.
Measure potassium loss in urine and replace accordingly.
(d) Syndrome of Inappropriate ADH Secretion (SIADH, Schwartz-Barter
syndrome)
Release of ADH in absence of physiologic (osmotic) stimuli.
Normal or increased intravascular volume, high urinary osmolality.
Seen in certain malignancies, many intracranial abnormalities and some
drugs. Symptoms of hyponatraemia and fluid overload.
First described with bronchogenic cancer.
Laboratory; Serum sodium < 134mEq/l, Serum osmolality low <280 mOsm/l
High urinary sodium >18 mEq/l
Definitive test; the water load test. Patient consumes water load 20ml/kg upto
1500 ml. Failure to excrete 65% of water load in 4 hours; 8% in 5 hours
positive. Risky test.
Treatment;
Acute SIADH; fluid restriction. If severe give hypertonic saline, furosemide
Chronic SIADH; fluid restriction, furosemide, phenytoin-inhibits ADH release.
Hypernatraemia:
Associated with Diabetes Insipidus; due to low levels of ADH (or, rarely, renal
insensitivity to ADH).
High out put of dilute urine with normal or high serum osmolality. Craving for
water. Risk of severe dehydration.
Aetiology
(i). Central Diabetes Insipidus (neurogenic). Reduced levels of ADH due to
hypothalamic-pituitary axis dysfunction. Postraumatic, post
transphenoidal/brain surgery, craniphayngioma, metastases, granuloma,
meningitis. Transient-settles within 12-36 hours. Prolonged in one third of
patients and may persist one year post surgery. Brain death; No ADH from
hypothalamus. Diagnosis; urine osmolarity 50-150 mOsm/L. SG 1001-1005
Urine output >250 cc/hr (paediatrics >3 cc/kg/hr), Normal or above normal
serum sodium, Normal adrenal function
Can be confirmed by water deprivation test
Treatment-Desmopressin.
(ii). Nephrogenic Diabetes Insipidus. Relative resistance of kidney to normal
levels of ADH. Drug related. Familial hypokalaemia. Hypercalcaemia.
Chronic renal disease.
Hyperkalaemia
41
Causes
i. Acute acidosis; hydrogen ions move into cells in exchange for
potassium.
ii. Reduced renal excretion.
iii. Adrenal insufficiency (Addisons disease)
iv. Potassium sparing diuretics
Treatment
i. Calcium gluconate 10%, 5-10 ml i.v. over 2 min. Antagonises
cardiac and neuromuscular toxicity.
ii. Sodium Bicarbonate; causes potassium to move into the cells within
15 minutes. 1 amp. i.v. (44mEqHCO3) over 5 minutes.
iii. Insulin and glucose infusion; moves potassium into cells within 30-
60 minutes. 5-10 U regular insulin in 1 amp Dextrose 50% (25 gm
dextrose), slow i.v. over 5 minutes.
iv. Cation exchange resins
v. Haemodialysis.
Hypokalaemia
Weakness, fatigability, myalgia, reduced reflexes, left ventricular failure,
dysarrhythmias, asystole,
ECG; T wave flattening in inversion, U waves.
Accompanied by low chloride levels.
Causes;
i. Reduced intake,
ii. gastrointestinal loss( vomiting, NG suction)
iii. renal loss (diuretics),
iv. acute alkalosis (H+ move out of cell in exchange for potassium- low
potassium.
Treatment
10 mEq KCl per hour. Avoid glucose solution (will lower potassium).
42
CHAPTER 6
FLUID MANAGEMENT FOR THE PEDIATRIC SURGICAL PATIENT

Introduction. Infants and children are very sensitive to small degrees of
dehydration.
Body-fluid composition
New-born term infant
The total body water content of a term gestation newborn is 75-80%. Total
body water decreases by 4-5% during the first week of life and is reflected in
weight loss. By age 1 year, total body water slowly decreases to the adult
levels of 60%. Extracellular water content decreases in parallel with total body
water content from 45% at term to 20-25% of adult levels by age 1 year.
For a premature neonate, both total body water and extracellular fluid (ECF)
increase with decreasing gestational age. For example, a premature
neonate's extracellular water content at 28-32 weeks' gestation is 52% of his
or her body weight. By age 1 week, the proportion of extracellular water
decreases 12%; neonate unloads in 1 week of life what would have taken 8
weeks in utero.
Changes in body-fluid compartments progress in an orderly fashion in utero,
but they are interrupted if a neonate is born prematurely. This reduction in
ECF volume is important in the normal transition from fetal to postnatal life.
Preterm infants with excess fluid intake have an increased incidence of patent
ductus arteriosus, left ventricular failure, respiratory distress, and necrotizing
enterocolitis.
Renal electrolyte and fluid physiology
The postnatal shift in body fluids is principally mediated through the kidneys'
regulation of water and sodium excretion. Renal handling of water is related to
glomerular filtration and tubular function. A term newborn's glomerular
filtration rate (GFR) is 25% of an adult's. A newborn's GFR rapidly rises during
the first week of life and then slowly increases to adult levels by age 2 years.
Despite this low GFR, term-gestation infants can handle large water loads
because the positive effect of the low concentrating capacity of the newborn
kidney counteracts the negative effect of the low GFR. However, premature
infants have limited compensatory mechanisms and may not tolerate large
water loads or hypovolemia without severe clinical complications.
The concentrating capacity of an infant's kidneys is less than an adult's. In
response to water deprivation, the kidney of a term infant can increase the
osmolality of urine to a maximum of 600-700 mOsm/kg. In contrast, maximum
urine osmolality in an adult is 1200 mOsm/kg. Variations in the release of
vasopressin or antidiuretic hormone (ADH) regulate the osmolality of ECF.
Although dehydrated newborns cannot concentrate urine as efficiently as
adults can, free water clearance is greater in infants than in adults. After a
free water load, infants can excrete markedly diluted urine of up to 50
mOsm/kg; in contrast, the maximally dilute urine in adults is 70-100 mOsm/kg.
Clinical states that can increase basal fluid requirements in the infant include
hyperthermia, increased evaporative losses from mechanical ventilation, and
altered transepithelial losses from premature gestational age. Simple
43
maneuvers to control these alterations of fluid balance include increasing
basal fluid replacement in infants with hyperthermia or in those placed under
bilirubin heating lamps and ensuring that all ventilator tubing is humidified.
The patient's state of hydration, renal function, and osmolar load determine
his or her urine output and concentration. Osmolar load consists of
endogenous and exogenous solutes that the kidney must clear to maintain
homeostasis. The volume of renal water must be sufficient for the kidney to
clear the osmolar load given its concentrating capacity.
Fluid management is divided into 3 phases: deficit therapy, maintenance
therapy, and replacement therapy.
Deficit therapy
Deficit therapy is the management of fluid and electrolyte losses that occur
before the patient's presentation. Deficit therapy has 3 components:
estimation of the severity of dehydration, determination of the type of fluid
deficit, and repair of the deficit.
The severity of dehydration is estimated from the patient's history and
physical condition. In children with mild dehydration (ie, loss of 1-5% of the
body fluid volume), findings are largely based on their history (eg, vomiting,
diarrhea), with minimal findings during physical examination. Children with
moderate dehydration (ie, 6-10% loss) have histories of fluid losses plus
physical findings that include tenting of the skin, weight loss, sunken eyes and
fontanel, slight lethargy, and dry mucous membranes. Most patients with
severe dehydration (ie, 11-15% loss) have cardiovascular instability (eg, skin
mottling, tachycardia, hypotension) and neurologic involvement (eg, irritability,
coma).
The type of fluid deficit can be estimated from the patient's history, physical
findings, electrolyte values, and serum tonicity. Types of dehydration are
isotonic (ie, serum osmolarity of 270-300 mOsm/L, serum Na+ concentration
of 130-150 mEq/L), hypotonic (ie, serum osmolarity of <270 mOsm/L, serum
Na+ concentration of <130 mEq/L), or hypertonic (ie, serum osmolarity of
>310 mOsm/L, serum Na+ concentration of >150 mEq/L). Patients with
hypertonic dehydration require special attention because complications, such
as cerebral edema, may occur during rehydration.
Restoration of cardiovascular function, CNS function, and renal perfusion are
the primary concerns in repair of fluid deficit. Initiate therapy with an isotonic
fluid volume expander. Total fluid-deficit repair may require considerable time.
In particular, potassium losses cannot be quickly replaced. After the child is
producing urine, add a small amount of potassium (<40 mEq/L) to the fluid.
Continually monitor the adequacy of deficit therapy by assessing the patient's
clinical condition, urine output, and urine specific gravity.
Rapid rehydration therapy
In volume-depleted children, increasing importance is being given to the use
of rapid replacement of ECF losses as opposed to classic deficit therapy, as
described above. For example, after severe burns, patients improve and
mortality rates decline with the rapid, generous expansion of ECF. The total
amount of fluid given in the first 6-12 hours is often approximately 100 mL/kg
of an ECF-type fluid, such as normal saline or lactated Ringer solution.
44
In describing rapid rehydration therapy, Friedman (2005) suggests that, in
children with moderate dehydration who cannot tolerate oral rehydration, ECF
should be rapidly restored by administering lactated Ringer solution at a
dosage of 40 mL/kg in 1-2 hours; oral rehydration should be started after the
intravenous (IV) infusion is completed. In patients with severe dehydration,
ECF should be rapidly restored by administering IV lactated Ringer
solution, 0.9% NaCl (ie, isotonic NaCl solution, normal saline), or both at a
rate of 40 mL/kg over 1-2 hours. If skin turgor, alertness, or pulse rate do not
return to normal by the end of the infusion, an additional dose of 20-40 mL/kg
should be infused over 1-2 hours.
Colloid versus crystalloid fluids
Both colloid and crystalloid solutions are widely used in the fluid resuscitation
of critically ill children. Several choices of colloid are available, including
albumin, hydroxyethyl starch (Hetastarch), and dextran.
Debate about the relative effectiveness of colloids compared with crystalloid
fluids (eg, Ringer lactate solution [RL], 0.9% NaCl solution) is ongoing. In a
recent Cochrane Database Review, investigators examined a series of
randomized and quasirandomized trials of colloids compared with crystalloids
in patients who required volume replacement. However, trials in neonates
were excluded. No evidence suggested that resuscitation with colloids
reduced the risk of death compared with resuscitation with crystalloids in
patients with trauma or burns or in those who underwent surgery.
Because colloids are not associated with improved survival and because they
are more expensive than crystalloids, their continued use in critically ill
patients is probably not justified outside the context of randomized controlled
trials.
Maintenance therapy
The aim of maintenance therapy is to replace water and electrolytes lost
under ordinary conditions. In the perioperative period, maintenance fluid
administration often does not sufficiently account for the increased fluid
requirements caused by third-space losses into the interstitium and gut. Table
1 outlines a plan for perioperative maintenance fluid therapy.
Table 17. Guide for Early Postoperative and Maintenance Therapy
Age <12 h After Surgery Maintenance Fluids

(mo)
<6 D10W with 0.45% NaCl at 1.5 times the D10W with 0.2% NaCl plus KCl 10-20 mEq/L at
maintenance rate maintenance rate
>6 D5W with Ringers Lactate solution at 1.5 times the D10W with 0.4% NaCl plus 10-20 mEq/L at
maintenance rate maintenance rate
Note: D10W = 10% dextrose in water, D5W = 5% dextrose in water.

The fluid for maintenance therapy replaces losses from 2 processes:
evaporative (ie, insensible) losses and urinary losses. Evaporative losses
consisted of solute-free water losses through the skin and lungs. Under
ordinary conditions, insensible losses account for approximately 30-35% of
total maintenance volume, and this free water represents approximately a
45
third of the total requirement for maintenance fluid. Ambient humidity and
temperature affect insensible losses. Patients receiving humidified air have
less insensible loss than those not receiving humidified air. Patients with
hyperthermia or tachypnea similarly have exaggerated insensible losses.
In a euvolemic state, urinary losses are 280-300 mOsm/kg of water, with a
specific gravity of 1.008-1.015. In some circumstances (eg, diabetes insipidus,
prematurity), the production of dilute urine is obligatory, and the volume of
maintenance fluids must be appropriately increased. In other circumstances
(eg, excessive ADH secretion, physiologic stress), a patient may be unable to
decrease urine osmolality to 300 mOsm/kg of water, and the volume of
maintenance fluids must be decreased. Under euvolemic conditions, urinary
losses account for two thirds of total maintenance fluids.
Total requirements for maintenance fluid can be estimated from common
formulas, such as those listed below. Frequently assess the patient's
condition during maintenance therapy. If the estimate is correct, the patient's
electrolyte levels should remain stable, and the patient should remain
clinically euvolemic. Abnormal electrolyte levels or clinical signs of
hypervolemia or hypovolemia indicate a need to reassess each component of
the patient's maintenance therapy.
A guide for maintenance fluid therapy for term infants and older children is as
follows:
Newborn
Day 1 - D10W infused at a rate of 50-60 mL/kg/d
Day 2 - D10W with 0.2% NaCl infused at a rate of 100 mL/kg/d
After day 7 - D5W with 0.45% NaCl or D10W with 0.45% NaCl infused at a
rate of 100-150 mL/kg/d
Child infusion rates
0-10 kg - 100 mL/kg/d (4 mL/kg/h)
10-20 kg - 1000 mL/d + 50 mL/kg/d (40 mL/h + 2 mL/kg/h)
Less than 20 kg - 1500 mL/d + 25 mL/kg/d (60 mL/h + 1 mL/kg/h)
Replacement therapy
Replacement fluid therapy is designed to replace ongoing abnormal fluid and
electrolyte losses. Because the constituents of these losses often
substantially differ from the composition of maintenance fluids, simply
increasing the volume of maintenance fluids to compensate for these losses
may be hazardous. The authors generally replace large-volume stoma or
other fluid losses with a physiologic equivalent fluid, as shown in Table 2.
As an alternative, measuring the electrolyte content of these losses and
replacing them milliequivalent for milliequivalent or milliliter for milliliter may be
preferred in select circumstances. For the patient under severe physiologic
stress or for those undergoing extensive surgery, calculate third-space losses
into the interstitium, and adjust replacement therapy accordingly.
46
Table 18 . Typical Electrolyte Composition of Body Fluids for a Child with Abnormal Fluid and Electrolyte Losses
and of Common IV Fluids
Body/iv Fluid ElectrolytesmEq--/L

Na K Cl HCO
Gastric 70 5-15 120 0
Pancreas 140 5 50-100 100
Bile 130 5 100 40
Ileostomy 130 15-20 120 25-30
Diarrheah 50 35 40 50
RL solution 130 4 109 28
0.9% NaCl 154 0 154 0
0.45% NaCl 77 0 77 0
47
CHAPTER 7
HYPOVOLAEMIC SHOCK
Grades of hypovolaemic shock
Grade 1: 15% blood volume (<750 ml), Mild resting tachycardia
Grade 2: 15 - 30% blood volume (750 - 1500 ml). Moderate tachycardia, fall in
pulse pressure, delayed capillary return.
Grade 3: 30 - 40% blood volume (1500 - 2000 ml). Hypotension, tachycardia,
low urine output
Grade 4: 40-50% blood volume (2000 -2500 ml). As above but with profound
hypotension
Fluid resuscitation
Early intravascular volume replacement in trauma patients is essential. The
ideal resuscitation fluid is uncertain. Timing and end-points of resuscitation
unclear.
Packed red blood cells.
Provide best volume expansion and oxygen carrying capacity
Needs cross-matching and not immediately available
Dilutional coagulopathy occurs with massive transfusion
Crystalloid versus colloid resuscitation
More than 40 randomised controlled trials of crystalloid vs. colloid
resuscitation published
None has shown either type of fluid to be associated with a reduction in
mortality
No single type of colloid has been shown to be superior
Albumin solution may be associated with slight increase in mortality Colloids
can more rapidly correct hypovolaemia
Also maintain intravascular oncotic pressure
Crystalloids require large volume but are equally effective
Cheaper and have fewer adverse side effects
Hypertonic solutions
Subjected to recent intensive investigation
Can resuscitate patient rapidly with a reduced volume of fluid
May reduce cerebral oedema in patients with severe head injuries
Oxygen therapeutic agents
Currently being extensively investigated in clinical trials
Not widely used at present outside of clinical trials
Potential advantages over blood include: Free potential viral contamination,
Longer shelf life, Universal ABO compatibility, Similar oxygen carrying
capacity to blood.
Agents being studied include: Perflurocarbons, Human haemoglobin
solutions, polymerised bovine haemoglobin
Intraosseous infusion:
Venous access can be difficult in the hypovolaemic child
If difficulty experienced then intraosseous route can be used as an alternative
Medullary canal in a child has a good blood supply
Drugs and fluids are absorbed into venous sinusoids of red marrow
48
Red marrow replaced by yellow marrow after 5 years of age
Less effective in older children
Systemic drug levels are similar to those achieved via the intravenous route
Technique is generally safe with few complications
Indications: Major trauma, Extensive burns, Cardiopulmonary arrest, Septic
shock
Contraindications: Ipsilateral lower limb fracture, Vascular injury
Technique: Intraosseous access achieved with specially designed needles,
Short shaft allows accurate placement within the medullary canal, Handle
allows controlled pressure during introduction
Usually inserted into anterio-medial border of tibia, 3 cm below tibial tubercle.
Correct placement checked by aspiration of bone marrow. Both fluids and
drugs can be administered. Fluid often needs to be administered under
pressure. Once venous access achieved intraosseous needle can be
removed
Complications; Needles are incorrectly placed or displaced in about 10%
patients, Tibial fracture, Compartment syndrome, Fat embolism, Skin
necrosis, Osteomyelitis
FLUID RESUSCITATION IN SHOCK
Almost all circulatory shock states require large-volume IV fluid replacement,
as does severe intravascular volume depletion (eg, from diarrhea or heat
stroke). Intravascular volume deficiency is acutely compensated by
vasoconstriction, followed over hours by migration of fluid from the
extravascular compartment to the intravascular, maintaining circulating
volume at the expense of total body water. However, this compensation is
overwhelmed after major losses.
Fluids
Choice of resuscitation fluid depends on the cause of the deficit.
Hemorrhage: Loss of RBCs diminishes oxygen-carrying capacity. However,
the body increases cardiac output to maintain oxygen delivery and also
increases oxygen extraction. These factors provide a safety margin of about 9
times the resting oxygen requirement. Thus, nonoxygen-carrying fluids (eg,
crystalloid or colloid solutions) may be used to restore intravascular volume in
mild to moderate blood loss. However, once Hb declines to < 7 g/dL, in the
absence of cardiac or cerebral vascular disease, oxygen-carrying capacity
must be restored by infusion of blood (or in the future by blood substitutes).
Patients with coronary or cerebral vascular disease require blood for Hb < 10
g/dL.
Crystalloid solutions for intravascular volume replenishment are typically
isotonic (eg, 0.9% saline or Ringer's lactate [RL]). H2O freely travels outside
the vasculature, so as little as 10% of isotonic fluid remains in the
intravascular space. With hypotonic fluid (eg, 0.45% saline), even less
remains in the vasculature and thus is not used for resuscitation. Both 0.9%
saline and RL are equally effective; RL may be preferred in hemorrhagic
shock because it somewhat minimizes acidosis. However, the Ca in RL may
interfere with concurrently infused drugs and may trigger clotting in transfused
blood unless the ratio of blood:RL is > 2:1. For patients with acute brain injury
49
and hemorrhagic shock, 0.9% saline is preferred. Hypertonic saline (7.5%) is
also an effective crystalloid; it shifts more volume from the extravascular
space and therefore requires lower absolute volume, which has practical
advantages in a pre-hospital setting.
Colloid solutions (eg, hydroxyethyl starch, albumin, dextrans) are also
effective for volume replacement during major hemorrhage. Despite
theoretical benefits over crystalloid, no differences in survival have been
proven. Albumin is the colloid of choice, although it may have a negative
inotropic effect. Both dextrans and hydroxyethyl starch may adversely affect
coagulation when > 1.5 L is given.
Blood typically is given as packed RBCs, which should be cross-matched, but
in an urgent situation, 1 to 2 units of type O Rh-negative blood are an
acceptable alternative. When > 1 to 2 units are transfused (eg, in major
trauma), blood is warmed to 37 C. Patients receiving > 8 to 10 units may
require replacement of clotting factors with infusion of fresh frozen plasma or
cryoprecipitate and platelet transfusion. Blood substitutes are O2-carrying
fluids that can be Hb-based or perfluorocarbons. Hb-based fluids may contain
free Hb that is liposome-encapsulated or modified (eg, by surface modification
or cross-linking with other molecules) to limit renal excretion and toxicity.
Because the antigen-bearing RBC membrane is not present, these
substances do not require cross-matching. They also can be stored > 1 yr,
providing a more stable source than banked blood. Perfluorocarbons are IV
carbon-fluorine emulsions that carry large amounts of O2. However, they
have not been proven to increase survival and cannot be given in amounts
sufficient to compensate for critical RBC losses.
Nonhemorrhagic hypovolemia: Isotonic crystalloid solutions are typically given
for intravascular repletion during shock and hypovolemia. Colloid solutions are
generally not used. Patients with dehydration and adequate circulatory
volume typically have a free water deficit, and hypotonic solutions (eg, D5
0.45% saline) are used.
Route and Rate of Fluid Administration
Standard, large (eg, 14- to 16-gauge) peripheral IV catheters are adequate for
most fluid resuscitation. With infusion pump, they typically allow infusion of 1 L
of crystalloid in 10 to 15 min and 1 unit of packed RBCs in 20 min. For
patients at risk of exsanguination, a large (eg, 8.5 French) central venous
catheter provides more rapid infusion rates; a pressure infusion device can
infuse 1 unit of packed RBCs in < 5 min.
Patients in shock typically require and tolerate infusion at the maximum rate.
Adults are given 1 L of crystalloid (20 mL/kg in children) or, in hemorrhagic
shock, 5 to 10 mL/kg of colloid or packed RBCs, and the patient is
reassessed. An exception is a patient with cardiogenic shock who typically
does not require large volume infusion.
Patients with intravascular volume depletion without shock can receive
infusion at a controlled rate, typically 500 mL/h. Children should have fluid
deficit calculated and replacement given over 24 h (12 in the first 8 h).
End point and Monitoring
50
The actual end point of fluid therapy in shock is normalization of oxygen
delivery. However, this parameter is not often measured directly. Surrogate
end points include clinical indicators of end-organ perfusion and
measurements of preload.
Adequate end-organ perfusion is best indicated by urine output of > 0.5 to 1
mL/kg/h. Heart rate, mental status, and capillary refill may be affected by the
underlying disease process and are less reliable markers. Because of
compensatory vasoconstriction, mean arterial pressure (MAP) is only a rough
guideline; organ hypoperfusion may be present despite apparently normal
values. An elevated arterial blood lactate level reflects hypoperfusion;
however, levels do not decline for several hours after successful resuscitation.
Sublingual tissue CO2 level responds more rapidly (eg, within minutes) and
may be a more useful indicator.
Central Venous Pressure: Because urine output does not provide a minute-to-
minute indication, measures of preload may be helpful in guiding fluid
resuscitation for critically ill patients. Central venous pressure (CVP) is the
mean pressure in the superior vena cava, reflecting right ventricular end-
diastolic pressure or preload. Normal CVP ranges from 2 to 7 mm Hg (3 to 9
cm H2O). A sick or injured patient with a CVP < 3 mm Hg is presumed to be
volume depleted and may be given fluids with relative safety. When the CVP
is within the normal range, volume depletion cannot be excluded, and the
response to 100- to 200-mL fluid boluses should be assessed; a modest
increase in CVP in response to fluid generally indicates hypovolemia. An
increase of > 3 to 5 mm Hg in response to a 100-mL fluid bolus suggests
limited cardiac reserve. A CVP > 12 to 15 mm Hg casts doubt on hypovolemia
as the sole etiology of hypoperfusion, and fluid administration risks fluid
overload.
Because CVP may be unreliable in assessing volume status or left ventricular
function, pulmonary artery catheterization may be considered for diagnosis or
for more precise titration of fluid therapy if there is no cardiovascular
improvement after initial therapy. Care must be taken when interpreting filling
pressures in patients during mechanical ventilation, particularly when positive
end-expiratory pressure (PEEP) levels exceeding 10 cm H2O are being used
or during respiratory distress when pleural pressures fluctuate widely.
Measurements are made at the end of expiration, and the transducer is
referenced to atrial zero levels (mid chest) and carefully calibrated.
Traumatic hemorrhagic shock: These patients may require a slightly different
approach. Experimental and clinical evidence indicates that internal
hemorrhage (eg, from visceral or vascular laceration or crush) may be
worsened by resuscitation to normal or supranormal MAP. Some physicians
advocate an MAP of 60 to 80 mm Hg as the resuscitation end point in such
patients pending surgical control of bleeding.
After blood loss is controlled, Hct is used to guide the need for further
transfusion. To minimize the use of blood products, a target Hct of 23 to 28%
is suggested. Patients who may have difficulty tolerating moderate anemia
(eg, those with coronary or cerebral artery disease) are kept above 30%. A
51
higher Hct does not improve outcome and, by causing increased blood
viscosity, may impair perfusion of capillary beds.
Complications
Overly rapid infusion of any type of fluid may precipitate pulmonary edema.
Hemodilution from crystalloid infusion is not of itself injurious, although Hct
must be monitored to note whether threshold values for transfusion are met.
RBC transfusion has a low risk of directly transmitting infection but in critically
ill patients, it seems to cause a slightly higher rate of hospital-acquired
infection. This risk may be minimized by using blood < 12 days old; such
RBCs are more plastic and less likely to cause sludging in the
microvasculature. Other complications of massive transfusion are discussed
elsewhere.
HAEMORRHAGIC SHOCK
Introduction
Hemorrhagic shock is a condition of reduced tissue perfusion, resulting in the
inadequate delivery of oxygen and nutrients that are necessary for cellular
function. Whenever cellular oxygen demand outweighs supply, both the cell
and the organism are in a state of shock.
On a multicellular level, the definition of shock becomes more difficult
because not all tissues and organs will experience the same amount of
oxygen imbalance for a given clinical disturbance. Clinicians struggle daily to
adequately define and monitor oxygen utilization on the cellular level and to
correlate this physiology to useful clinical parameters and diagnostic tests.
The 4 classes of shock, as proposed by Alfred Blalock in 1934, are as follows:
Hypovolemic
Vasogenic (septic)
Cardiogenic
Neurogenic
Hypovolemic shock, the most common type, results from a loss of circulating
blood volume from clinical etiologies, such as penetrating and blunt trauma,
gastrointestinal bleeding, and obstetrical bleeding. Humans are able to
compensate for a significant hemorrhage through various neural and
hormonal mechanisms. Modern advances in trauma care allow patients to
survive when these adaptive compensatory mechanisms become
overwhelmed.
Pathophysiology
Well described responses to acute loss of circulating volume exist.
Teleologically, these responses act to systematically divert circulating volume
away from nonvital organ systems so that blood volume may be conserved for
vital organ function. Acute hemorrhage causes a decreased cardiac output
and decreased pulse pressure. These changes are sensed by baroreceptors
in the aortic arch and atrium. With a decrease in the circulating volume, neural
reflexes cause an increased sympathetic outflow to the heart and other
organs. The response is an increase in heart rate, vasoconstriction, and
redistribution of blood flow away from certain nonvital organs such as the skin,
gastrointestinal tract, and kidneys.
52
Concurrently, a multisystem hormonal response to acute hemorrhage occurs.
Corticotropin-releasing hormone is stimulated directly. This eventually leads to
glucocorticoid and beta-endorphin release. Vasopressin from the posterior
pituitary is released, causing water retention at the distal tubules. Renin is
released by the juxtamedullary complex in response to decreased mean
arterial pressure, leading to increased aldosterone levels and eventually to
sodium and water resorption. Hyperglycemia commonly is associated with
acute hemorrhage. This is due to a glucagon and growth hormoneinduced
increase in gluconeogenesis and glycogenolysis. Circulating catecholamines
relatively inhibit insulin release and activity, leading to increased plasma
glucose.
In addition to these global changes, many organ-specific responses occur.
The brain has remarkable autoregulation that keeps cerebral blood flow
constant over a wide range of systemic mean arterial blood pressures. The
kidneys can tolerate a 90% decrease in total blood flow for short periods of
time. With significant decreases in circulatory volume, intestinal blood flow is
dramatically reduced by splanchnic vasoconstriction. Early and appropriate
resuscitation may avert damage to individual organs as adaptive mechanisms
act to preserve the organism.
Age
Hemorrhagic shock is tolerated differently, depending on the preexisting
physiologic state and, to some extent, the age of the patient. Very young and
very old people are more prone to early decompensation after loss of
circulating volume.
Pediatric patients have smaller total blood volumes and, therefore, are at risk
to lose a proportionately greater percentage of blood on an equivalent-volume
basis during exsanguination compared to adults. The kidneys of children
younger than 2 years are not mature; they have a blunted ability to
concentrate solute. Younger children cannot conserve circulating volume as
effectively as older children. Also, the body surface area is increased relative
to the weight, allowing for rapid heat loss and early hypothermia, possibly
leading to coagulopathy.
Elderly people may have both altered physiology and preexisting medical
conditions that may severely impair their ability to compensate for acute blood
loss. Atherosclerosis and decreased elastin cause arterial vessels to be less
compliant, leading to blunted vascular compensation, decreased cardiac
arteriolar vasodilation, and angina or infarction when myocardial oxygen
demand is increased. Older patients are less able to mount a tachycardia in
response to decreased stoke volume because of decreased beta-adrenergic
receptors in the heart and a decreased effective volume of pacing myocytes
within the sinoatrial node. Also, these patients frequently are treated with a
variety of cardiotropic medications that may blunt the normal physiological
response to shock. These include beta-adrenergic blockers, nitroglycerin,
calcium channel blockers, and antiarrhythmics.
The kidneys also undergo age-related atrophy, and many older patients have
significantly decreased creatinine clearance in the presence of near-normal
serum creatinine. Concentrating ability may be impaired by a relative
53
insensitivity to antidiuretic hormone. These changes in the heart, vessels, and
kidneys can lead to early decompensation after blood loss. All of these factors
in concert with comorbid conditions make management of elderly patients with
hemorrhage quite challenging.
History
No single historical feature is diagnostic of shock. Some patients may report
fatigue, generalized lethargy, or low back pain (ruptured abdominal aortic
aneurysm). Others may arrive by ambulance or in the custody of law
enforcement for the evaluation of bizarre behavior.
Obtaining a clear history of the type, amount, and duration of bleeding is very
important. Many decisions in regard to diagnostic tests and treatments are
based on knowing the amount of blood loss that has occurred over a specific
time period.
If the bleeding occurred at home or in the field, an estimate of how much
blood was lost is helpful.
For GI bleeding, knowing if the blood was per rectum or per os is important.
Because it is hard to quantitate lower GI bleeding, all episodes of bright red
blood per rectum should be considered major bleeding until proven otherwise.
Bleeding because of trauma is not always identified easily. The pleural space,
abdominal cavity, mediastinum, and retroperitoneum are all spaces that can
hold enough blood to cause death from exsanguination.
External bleeding from trauma can be significant and can be underestimated
by emergency medical personnel.
Scalp lacerations are notorious for causing large underestimated blood loss.
Multiple open fractures can lead to the loss of several units of blood.
Physical
The physical examination in patients with hemorrhagic shock is a directed
process. Often, the examination will be paramount in locating the source of
bleeding and will provide a sense of the severity of blood loss. Differences
exist between medical patients and trauma patients in these regards. Both
types of patients usually will require concurrent diagnosis and treatment.
The hallmark clinical indicators of shock have generally been the presence of
abnormal vital signs, such as hypotension, tachycardia, decreased urine
output, and altered mental status. These findings represent secondary effects
of circulatory failure, not the primary etiologic event. Because of
compensatory mechanisms, the effects of age, and use of certain
medications, some patients in shock will present with a normal blood pressure
and pulse. However, a complete physical examination must be performed with
the patient undressed.
The general appearance of a patient in shock can be very dramatic. The skin
may have a pale, ashen color, usually with diaphoresis. The patient may
appear confused or agitated and may become obtunded.
The pulse first becomes rapid and then becomes dampened as the pulse
pressure diminishes. Systolic blood pressure may be in the normal range
during compensated shock.
The conjunctivae are inspected for paleness, a sign of chronic anemia. The
nose and pharynx are inspected for blood.
54
The chest is auscultated and percussed to evaluate for hemothorax. This
would lead to loss of breath sounds and dullness to percussion on the side of
bleeding.
The abdominal examination searches for signs of intra-abdominal bleeding,
such as distention, pain with palpation, and dullness to percussion. The flanks
are inspected for ecchymosis, a sign of retroperitoneal bleeding. Ruptured
aortic aneurysms are one of the most common conditions that cause patients
to present in unheralded shock. Signs that can be associated with a rupture
are a palpable pulsatile mass in the abdomen, scrotal enlargement from
retroperitoneal blood tracking, lower extremity mottling, and diminished
femoral pulses.
The rectum is inspected. If blood is noted, take care to identify internal or
external hemorrhoids. On rare occasion, these are a source of significant
bleeding, most notably in patients with portal hypertension.
Patients with a history of vaginal bleeding undergo a full pelvic examination. A
pregnancy test is warranted to rule out ectopic pregnancy.
Trauma patients are approached systematically, using the principles of the
primary and secondary examination. Trauma patients may have multiple
injuries that need attention concurrently, and hemorrhage may accompany
other types of insults, such as neurogenic shock.
The primary survey is a quick maneuver that attempts to identify life-
threatening problems.
To assess the airway, ask the patient's name. If the answer is articulated
clearly, the airway is patent.
The oral pharynx is inspected for blood or foreign materials.
The neck is inspected for hematomas or tracheal deviation.
The lungs are auscultated and percussed for signs of pneumothorax or
hemothorax.
The radial and femoral pulses are palpated for strength and rate.
A quick inspection is made to rule out any external sources of bleeding.
A gross neurological examination is performed by asking the patient to
squeeze each hand and dorsiflex both feet against pressure. Advanced
trauma life support (ATLS) suggests that a "miniature" neurologic examination
categorizes the patient's level of consciousness by whether the patient is
alert, responds to voice, responds to pain, or is unresponsive (ie, AVPU).
The patient then is exposed completely, taking care to maintain
thermoregulation with blankets and external warming devices.
The secondary examination is a head-to-toe, careful examination that
attempts to identify all injuries.
The scalp is inspected for bleeding. Any active bleeding from the scalp should
be controlled before proceeding with the examination.
The mouth and pharynx are examined for blood.
The abdomen is inspected and palpated. Distention, pain on palpation, and
external ecchymosis are indications of intra-abdominal bleeding.
The pelvis is palpated for stability. Crepitus or instability may be an indication
of a pelvis fracture, which can cause life-threatening hemorrhage into the
retroperitoneum.
55
Long bone fractures are noted by localized pain to palpation and boney
crepitus at the site of fracture. All long bone fractures should be straightened
and splinted to prevent ongoing bleeding at the sites. Femur fractures are
especially prone to large blood losses and should be immobilized immediately
in a traction splint.
Further diagnostic tests are warranted to diagnose intrathoracic, intra-
abdominal, or retroperitoneal bleeding.
Causes
Hemorrhagic shock is caused by the loss of both circulating blood volume and
oxygen-carrying capacity. The most common clinical etiologies are
penetrating and blunt trauma, gastrointestinal bleeding, and obstetrical
bleeding.
Investigations.
Lab Studies
Generally, laboratory values are not helpful in acute hemorrhage because
values do not change from normal until redistribution of interstitial fluid into the
blood plasma occurs after 8-12 hours. Many of the derangements that
eventually occur are a result of replacing a large amount of autologous blood
with resuscitation fluids.
Hemoglobin and hematocrit values remain unchanged from baseline
immediately after acute blood loss. During the course of resuscitation, the
hematocrit may fall secondary to crystalloid infusion and re-equilibration of
extracellular fluid into the intravascular space.
No absolute threshold hematocrit or hemoglobin level that should prompt
transfusion exists. A hemoglobin concentration of less than 7 g/dL in the acute
setting in a patient that was otherwise healthy is concerning only because the
value most likely will drop considerably after re-equilibration.
In the absence of preexisting disease, transfusions can be withheld until
significant clinical symptoms are present or the rate of hemorrhage is enough
to indicate ongoing need for transfusion.
Patients with significant heart disease are at higher risk of myocardial
ischemia with anemia, and transfusion should be considered when values
drop below 7 mg/dL.
Arterial blood gas may the most important laboratory value in the patient in
severe shock.
Acidosis is the best indicator in early shock of ongoing oxygen imbalance at
the tissue level. A blood gas with a pH of 7.30-7.35 is abnormal but tolerable
in the acute setting. The mild acidosis helps unload oxygen at the peripheral
tissues and does not interfere with hemodynamics.
A pH below 7.25 may begin to interfere with catecholamine action and cause
hypotension unresponsive to inotropics. Although this is a time-honored
concept, recent data do not find evidence of this phenomenon.
Metabolic acidosis is a sign of underlying lack of adequate oxygen delivery or
consumption and should be treated with more aggressive resuscitation, not
exogenous bicarbonate. Life-threatening acidemia (pH <7.2) initially may be
buffered by the administration of sodium bicarbonate to improve the pH.
56
However, be aware that no survival benefit to this practice has been
documented.
Coagulation studies generally produce normal results in the majority of
patients with severe hemorrhage early in the course. The notable exceptions
are patients who are on warfarin, low molecular weight heparin, or antiplatelet
medications or those patients with severe preexisting hepatic insufficiency.
If patients are unable to provide adequate medication histories, tests for
primary and secondary hemostasis should be ordered. The prothrombin time
(PT) and the activated partial thromboplastin time (aPTT) will identify major
problems with secondary hemostasis.
The best test for platelet function is the bleeding time. This test is difficult to
perform in the patient with acute hemorrhage.
An alternative is thromboelastography, which is at least equivalent, and
possibly superior, to the bleeding time. This test is an ex vivo analysis of all of
the components of clotting and has been used extensively in orthotopic
hepatic transplantation, cardiac surgery, and trauma.
Qualitative platelet dysfunction can be inferred in those patients with a clinical
coagulopathy and normal PT and aPTT values. Obviously, abnormal PT or
aPTT values should be corrected emergently in the context of severe
hemorrhage.
Electrolyte studies usually are not helpful in the acute setting. After massive
resuscitation, certain abnormalities can occur.
Sodium and chloride may increase significantly with administration of large
amounts of isotonic sodium chloride. Hyperchloremia may cause a nonion
gap acidosis and significantly worsen an existing acidosis.
Calcium levels may fall with large-volume, rapid blood transfusions. This is
secondary to chelation of the calcium by the ethylenediaminetetraacetic acid
(EDTA) preservative in stored blood. Newer methods of blood banking avoid
using EDTA, and the problem of hypocalcemia should be minimized.
Likewise, potassium levels may rise with large-volume blood transfusions.
Creatinine and blood urea nitrogen usually are within normal limits unless
preexisting renal disease is present. Caution should be used when
administering iodinated contrast in patients with elevated creatinine because
the dye load could initiate a contrast-induced nephropathy in addition to
chronic renal impairment.
A blood specimen for type and crossmatch should be obtained as soon as the
patient arrives.
For patients who are actively bleeding, 4 U of packed red blood cells (PRBCs)
should be prepared, along with 4 U of fresh frozen plasma (FFP). Platelets
may be obtained as well, depending on the physician's estimation of the
likelihood of the need for platelet transfusion (less commonly needed
compared to FFP).
Imaging Studies
Imaging studies are aimed at identifying the source of bleeding. In many types
of severe hemorrhage, therapeutic interventions, such as exploratory
laparotomy, will preclude comprehensive diagnostic studies.
Chest radiographs
57
Chest radiographs indicate a diagnosis of hemothorax by showing a large
opacity in one or both lung fields.
Hemothoraces large enough to cause shock usually are obvious as a
complete whiteout of one pleural space.
Abdominal radiographs
Abdominal radiographs are rarely helpful. Hemoperitoneum usually will not be
visible on plain film.
Occasionally, a radiograph will have a diffuse ground glass appearance,
suggesting a large amount of intraperitoneal fluid, but this sign is not reliable.
Rarely, a ruptured abdominal aortic aneurysm can be diagnosed by noting an
incomplete shell (calcified wall) of a dilated aorta.
Loss of the psoas shadow unilaterally also can suggest retroperitoneal blood.
Computed tomography scan
Computed tomography (CT) scan is sensitive and specific for diagnosing
intrathoracic, intra-abdominal, and retroperitoneal bleeding. It is the test of
choice for diagnosing bleeding in these cavities.
CT scan only has an adjunctive role in the diagnosis of GI bleeding when
other tests have suggested a mass lesion as part of the disease process.
Ultrasound is rapidly replacing CT scan as the diagnostic test of choice for the
identification of hemorrhage in major body cavities. It is, of course, limited in
its ability to evaluate the retroperitoneum. Retroperitoneal evaluation remains
the purview of the CT scan.
Esophagogastroduodenoscopy
Esophagogastroduodenoscopy (EGD) is the test of choice for acute upper GI
bleeding because it can provide a specific diagnosis and has therapeutic
potential.
Lavage the stomach with a large gastric tube before the procedure to remove
as much clot as possible.
Capabilities for epinephrine injection and bipolar circumactive probe (BICAP)
cautery should be available.
Aortoenteric fistulas are very rare and usually are caused by erosion of an
aortic aneurysm into the duodenum. EGD may be able to diagnose this
problem, but the false-negative rate in these cases is very high.
Colonoscopy
Colonoscopy is used to diagnose acute lower GI bleeding.
It is considered by most to be difficult to perform in the acute setting and may
fail to show the exact source of bleeding in cases of rapid hemorrhage.
Although some experience exists with therapeutic interventions, such as
cauterization for acute arteriovenous malformation bleeding, these techniques
are not used widely.
Ultrasound
Ultrasound is a useful technique to diagnose intraperitoneal bleeding in the
trauma patient.
The focused abdominal sonographic technique (FAST) examination
realistically has replaced diagnostic peritoneal lavage as the test of choice for
identifying intraperitoneal fluid in the trauma patient.
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The FAST examination includes 4 anatomical views of the pericardium,
abdomen, and pelvis that attempt to identify free intra-abdominal fluid.
Bedside ultrasound can be performed by radiologists, surgeons, and
emergency medicine physicians who have specialized training and
certification.
Angiography is extremely useful in the diagnosis of acute hemorrhage from
many different sources. Its utility is limited by the availability of an
angiographer on a timely basis.
In cases of lower GI bleeding, angiography is one of the best tests to localize
a bleeding source. Angiography usually can detect bleeding that is at least 1-2
mL/min. Selective angiograms of the celiac, superior mesenteric, and inferior
mesenteric arteries are performed to locate the areas of bleeding. The best
time to perform the examination is when the patient is actively bleeding. Once
the source is identified, embolotherapy may be used as an acute means of
arresting hemorrhage. This will allow resuscitation to proceed prior to
operation. If embolotherapy is not used, then identifying the site of bleeding
will allow a more limited bowel resection to be performed if surgery becomes
indicated during the admission.
Angiography can be used for diagnosis and management of severe bleeding
from pelvic fractures. Although most bleeding from severe pelvic fractures is
venous in origin, occasional significant arterial bleeding can be diagnosed and
treated effectively with embolization.
Severe liver injuries pose a challenge to the trauma surgeon because of the
large amounts of blood loss and the difficulty in gaining surgical control
quickly. Many severe liver injuries now are being diagnosed and treated with
angiographic embolization. Angiography is increasingly considered first-line
intervention (before laparotomy) for severe liver injuries in centers that are
equipped to perform rapid angiography and angiographic intervention. Similar
methods may be used for other solid organ injuries, such as the spleen and
kidney.
Angiography may be used in the diagnosis of massive hemoptysis of unclear
etiology. Selective angiography of the bronchial arteries, combined with a
selective pulmonary angiogram through a separate venous catheterization
can localize bleeding.
The role of angiography in upper GI bleeding is more limited. Hemobilia is a
rare cause of upper GI bleeding. If blood definitely is observed emanating
from the ampulla of Vater, angiography should be performed to localize and
control the source of bleeding.
Nuclear medicine scanning can be used to localize GI bleeding.
A tagged red blood cell scan may help differentiate upper from lower GI
bleeding and may provide anatomic information, such as identifying bleeding
from the right versus left colon. Overlap of structures will confound the utility
and accuracy of this test.
The test requires a significant amount of time to complete, but it is very
sensitive, detecting bleeding as slow as 0.5 mL/min.
Procedures
59
Diagnostic peritoneal lavage is a bedside procedure that utilizes a small
midline laparotomy and insertion of a catheter directly into the peritoneal
cavity. Percutaneous insertion techniques are available but carry an increased
risk of injury to underlying structures.
The intent of diagnostic peritoneal lavage is to determine if significant intra-
abdominal bleeding or injuries to hollow organs are present.
If more than 5 mL of blood is aspirated, the test result is said to be grossly
positive and laparotomy usually is indicated.
If blood is not aspirated, 1000 mL of warm lactated Ringer solution is infused
into the abdomen and then allowed to drain out into the IV bag. The contents
of the bag are examined in the lab. A red blood cell count of greater than
10,000 per L is considered a microscopically positive test result.
Other conditions that make the test results positive include the following: white
blood cell count greater than 500/L; high levels of amylase, lipase, or
bilirubin; and particulate matter that may be from an intraluminal source.
Central venous access
Central venous access is considered an adjunct to large-bore (16- or 14-
gauge) peripheral IV lines.
Flow through a catheter is inversely proportional to the length and directly
proportional to the diameter. Thus, long small-caliber lines, such as a
standard triple lumen catheter, will deliver significantly less volume than a
short large-caliber line, such as a peripheral IV.
Large-bore (12F) central resuscitation lines
This is a large-bore sheath introducer used for volume resuscitation. Smaller
sizes are less effective but are more effective than a standard multi-lumen
central venous catheter.
If significant intra-abdominal bleeding from a venous injury is suspected,
volume lines should be avoided in the femoral veins.
In general, access above and below the site of an injury is a good practice.
This allows the operator to switch the primary resuscitation lines should one
or more be ineffective or be positioned directly below an injury in the vessel in
which the catheter resides.
Chest tube
The initial management of a hemothorax involves the insertion of a large-
caliber chest tube for drainage, or open thoracotomy. In most patients with a
hemothorax, tube thoracostomy alone is sufficient.
Surgical exploration with open thoracotomy is mandated in the presence of
persistent bleeding; the presence of more than 1500 mL of blood in the initial
chest tube drainage; or drainage of more than 200 mL/h for 2-4 hours.
Treatment
Medical Care
The primary treatment of hemorrhagic shock is to control the source of
bleeding as soon as possible and to replace fluid.
In controlled hemorrhagic shock (CHS) where the source of bleeding has
been occluded, fluid replacement is aimed toward normalization of
hemodynamic parameters. In uncontrolled hemorrhagic shock (UCHS) in
which bleeding has temporarily stopped because of hypotension,
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vasoconstriction, and clot formation, fluid treatment is aimed at restoration of
radial pulse, or restoration of sensorium or obtaining a blood pressure of 80
mm Hg by aliquots of 250 mL of lactated Ringer's solution (hypotensive
resuscitation).
When evacuation time is shorter than 1 hour (usually urban trauma),
immediate evacuation to a surgical facility is indicated after airway and
breathing (A, B) have been secured ("scoop and run"). Precious time is not
wasted by introducing an intravenous line. When expected evacuation time
exceeds 1 hour, an intravenous line is introduced and fluid treatment is
started before evacuation. The resuscitation should occur before, or
concurrently with, any diagnostic studies.
Crystalloid is the first fluid of choice for resuscitation. Immediately administer
2 L of isotonic sodium chloride solution or lactated Ringer solution in response
to shock from blood loss. Fluid administration should continue until the
patient's hemodynamics become stabilized. Because crystalloids quickly leak
from the vascular space, 3 L of fluid need to be administered to raise the
intravascular volume by 1 L.
Alternatively, colloids restore volume in a 1:1 ratio. Currently available colloids
include human albumin, hydroxy-ethyl starch products (mixed in either 0.9%
isotonic sodium chloride solution or lactated Ringer solution), or the
hypertonic saline-dextran combinations. The sole product that is avoided
routinely in large-volume (>1500 mL/d) restoration is the hydroxy-ethyl starch
product mixed in 0.9% isotonic sodium chloride solution because it has been
associated with the induction of coagulopathy. The other products have not
been so implicated.
PRBCs should be transfused if the patient remains unstable after 2000 mL of
crystalloid resuscitation. For acute situations, O-negative noncrossmatched
blood should be administered. Administer 2 U rapidly and note the response.
For patients with active bleeding, several units of blood may be necessary.
If at all possible, blood and crystalloid infusions should be delivered through a
fluid warmer.
A blood sample for type and cross should be drawn, preferably before blood
transfusions are begun. Start type-specific blood when available.
Patients who require large amounts of transfusion inevitably will become
coagulopathic. FFP generally is infused when the patient shows signs of
coagulopathy, usually after 6-8 U of PRBCs.
Platelets become depleted with large blood transfusions.
Platelet transfusion also is recommended when a coagulopathy develops.
Surgical Care
The decision regarding whether to operate to control bleeding is complicated
and beyond the scope of this review. Some generalities, however, may be
advanced.
Acute life-threatening bleeding within the abdominal or thoracic cavity is an
indication for operation.
Retroperitoneal bleeding is difficult to control operatively and generally is
treated nonoperatively.
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Severe upper GI bleeds should be managed first by EGD, with the possibility
of cauterizing or injecting the bleeding source with epinephrine. Failure of
endoscopic management usually is an indication for surgery.
Confirm the location of a lower GI bleed before operative intervention is
performed.
Severe vaginal bleeding should prompt early involvement of the gynecologist.
Ectopic pregnancies are treated with immediate surgery.
Abruptio placenta is a true emergency and should prompt immediate
cesarean section.
Consultations
On occasion, consultation with a hematologist is essential. This especially is
true if the coagulopathy fails to be corrected with standard measures.
Increasingly recognized are the entities of heparin-induced thrombocytopenia
and acquired antibodies to native clotting factors. Consultation is useful in
identifying the correct tests to obtain, as well as the full range of useful
modalities to correct the underlying defect. These may include IV gamma-
globulin infusion, plasmapheresis, or, simply, large-volume clotting factor
repletion.
Follow-up
Further Inpatient Care
The remainder of care will be determined by the proximate course of the
hemorrhagic shock.
Patients with hemorrhagic shock are at risk for acute tubular necrosis, acute
lung injury, transfusion-related acute lung injury, infections (principally
nosocomial and related to operative sites or indwelling catheters), and
multiple organ dysfunction syndrome, with its attendant risk of death.
Discussion of each of these entities is beyond the scope of this chapter.
In/Out Patient Meds
Patients with hemorrhagic shock often are unable to mount an appropriate
bone marrow response in the acute setting with regard to red blood cell
production. Using erythropoietin (40,000 U/wk) in combination with
supplemental iron and vitamin C to boost production is useful. This strategy
has been used successfully to decrease red blood cell transfusions in a large
multicenter trial in Canada.
Transfer
In general, few indications exist to transfer a patient who is in shock to a
specialized facility. Ideally, all hospitals and physicians should be prepared to
initially treat and stabilize the patient with exsanguinating hemorrhage. After
control of the bleeding and reversal of acute shock, patients may be
transferred to facilities that can treat additional injuries.
The patient should be transferred by an advanced life support unit with the
capability of blood transfusion en route.
The decision for air ambulance transport instead of ground transportation is
one that involves consideration of proximity, difficulty with the ground route,
time en route, weather conditions, and availability.
Patients may be transferred for ongoing management of the initial injury when
the injury complex demands care that exceeds the resources or capabilities of
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the initially receiving facility. This transfer should be made from the
transferring physician to the receiving physician without intermediaries.
Complications
The primary complication is death.
The entire spectrum of organ failures may be the sequelae of resuscitated
hemorrhagic shock.
The cascade of systemic inflammatory response syndrome (SIRS)
progressing to multiple organ failure syndrome (described by the late Roger
Bone, MD) will complicate the cases of approximately 30-70% of patients who
present with hemorrhagic shock and survive their initial resuscitation.
Prognosis
Prognosis is related to the ability to be resuscitated from shock, as well as the
underlying illness or injury, not the presentation of hemorrhagic shock.
Special Concerns
Blood substitute: There are recognized risks associated with the transfusion of
large quantities of packed red blood cells. As a result, other modalities are
being investigated. One such modality is hemoglobin-based oxygen carriers
(HBOC). Clinical application has been limited by its toxic effect profile.
However, research is ongoing on the use of these products.
Hypertonic saline: In patients with hemorrhagic shock, hypertonic saline has
the theoretical benefit of increasing intravascular volume with only small
amounts of fluid. The combination of dextran and hypertonic saline may be
beneficial in situations where infusion of large volumes of fluid may be
harmful, such as in the elderly with impaired cardiac activity. Additional trials
will be required before this combination is accepted as standard of care.
RENAL FAILURE
Reduction in renal excretory or regulatory function
Results in the retention of waste products normally excreted by the kidney
Normal adult urine output = 0.5 ml/kg/hr
Renal failure can be: anuric, oliguric, polyuric
Causes of acute renal failure;
Pre-renal failure
Hypovolaemia secondary to acute blood or plasma loss, Fluid and electrolyte
depletion, Hypotension secondary to cardiogenic shock , Hypotension
secondary to sepsis, Acute tubular necrosis due to prolonged renal
hypoperfusion, Acute tubular necrosis due to contrast nephropathy,
Intrinsic renal failure
Acute glomerulonephritis, Drug induced nephrotoxic damage, Athero-embolic
disease, Acute pyelonephritis
Renal outflow obstruction
Calculi, Blood clot , Ureteric damage and ligation, Prostatic hypertrophy
Biochemical changes of acute renal failure; Hyponatraemia, Hyperkalaemia,
Hypocalcaemia, Metabolic acidosis
Urinary biochemistry
In pre-renal failure; Urine specific gravity - >1.016, Low urinary sodium - <20
mmol/l, High urinary urea - >250 mmol/l, High osmolality - > 500 mosm/kg
63
In intrinsic renal failure; Urine specific gravity - <1.010, High urinary sodium -
>40 mmol/l, Low urinary urea - <185 mmol/l, Isotonic urine - 300-350
mosm/kg Management of renal failure
Remove precipitating cause
Most surgical patients are hypovolaemic; require volume resuscitation, if
inadequate perfusion pressure consider inotropic support, oxygen
Consider bicarbonate if ; Base excess > 10, arterial pH <7
Hyperkalaemia; Requires urgent treatment if symptomatic, ECG changes -
increased pr interval, tented t waves, ventricular tachycardia, serum
potassium > 6 mmol/l
Treatment options ; 10 ml 10% calcium chloride intravenously, 10u Actrapid in
50 ml 50% dextrose, Salbutamol nebuliser, Calcium resonium 15-30 mg pr
twice daily
64
CHAPTER 8
ACID-BASE BALANCE DISORDERS IN SURGERY

Blood pH is normally maintained at 7.36-7.44
pH is a logarithmic scale
A change in pH of 0.3 units is equivalent to a doubling of hydrogen ion
concentration
pH is maintained by biological buffering mechanisms involving;
Proteins
Bicarbonate
Haemoglobin
The relationship between serum pH and bicarbonate concentration is simple
Described by the Henderson-Hasselbach equation
Compensatory mechanisms exist to compensate for changes in pH
Blood gas analysis;
Blood gas analyser measures
Partial pressure oxygen
Partial pressure carbon dioxide
pH
Other variables are derived using Henderson-Hasselbach equation
Table 19.Variables derived from a blood gas analyser
Variable Normal value

Temperature 37 degrees
pH 7.36-7.44
Partial pressure carbon dioxide 4.6-5.6 kPa
Partial pressure oxygen 10.0-13.3 kPa
Bicarbonate 22-26 mmol/l
Total carbon dioxide 24-28 mmol/l
Standard bicarbonate (SBC) 22-26 mmol/l
Base excess (BE) -2+2 mmol/l
Standard base excess (SBE) -3+3 mmol/l
Oxygen saturation >95%
Hemoglobin 11.5-16.5 g/dl
Definitions
Acidosis = a rise serum in hydrogen ion concentration or fall in pH (pH<7.3)
Alkalosis = a reduction in hydrogen ion concentration or rise in pH (pH>7.5)
Respiratory acidosis = a fall in pH due to a rise in partial pressure of carbon
dioxide
Respiratory alkalosis = a rise in pH due to a fall in partial pressure of carbon
dioxide
Metabolic acidosis = a fall in pH due to a metabolic cause
Metabolic alkalosis = a rise in pH due to a metabolic cause
Anion Gap: Used to distinguish metabolic acidosis from bicarbonate loss from
that of lactic acidosis.
Cations = sodium and potassium
Anions = chloride, bicarbonate
65
Difference between the two is the anion gap
If metabolic acidosis is due to anion excess the anion gap is increased
If metabolic acidosis is due to bicarbonate loss the anion gap is normal
Lactic acidosis and renal failure are associated with an increased anion gap
Interpretation of results
Interpret results with knowledge of the patients clinical condition
Check for the consistency within the blood gas sample
Look at the pH for the primary acid-base disorder
Assess a respiratory component by looking at the partial pressure of carbon
dioxide
Assess the metabolic component by looking at the BE or SBE
Calculate the anion gap
Water becomes alkaline with reduced temperature and acidic with increased
temperature
Physiologic pH:
Intracellular 6.9
Compartment 7.4
Venous 7.5
Arterial 7.4
Acid base balance refers to changes in hydrogen ion concentration in arterial
blood which reflects extracellular fluid (ECF), 7.4. Cells relatively impervious
to ionic materials and changes in fluids, electrolytes and carbon dioxide
tension easily alter the ECF.
Acidosis pH< 7.3 (increase H+ concentration)
Alkalosis pH>7.5 (decreased H+ concentration)
Strong ions: completely dissociated at physiologic pH; sodium, chloride,
potassium, sulphate, magnesium, calcium.
Strong ion difference; charge difference between strong cations and strong
anions
SID= [Na+] + [K+] + [Ca++] + [Mg++] - [Cl-] + [other strong anions A] = 40-44
mEq
Balanced by an equal amount of buffer base (phosphate, albumin and
bicarbonate)
A rise in SID will decrease hydrogen ion liberation from water; alkalosis
A fall in SID will increase hydrogen ion liberation; acidosis
Weak acids:
Albumin. Phosphate. Their degree of dissociation is related to temperature
and pH changes in hepatic and kidney failure. Hyperphosphataemia leads to
metabolic acidosis.
Carbon dioxide:
Major source of acid in the body. By-product of aerobic metabolism.
Concentration in extracellular fluid is determined by tissue production and
alveolar ventilation. Dissolved carbon dioxide exists as carbon dioxide,
carbonic acid, bicarbonate ions, carbonate ions.
Its a volatile acid buffered by haemoglobin (deoxyhaemoglobin-a strong
base) before elimination. In chronic respiratory acidosis there is raised level of
carbon dioxide and serum bicarbonate/
66
Regulation of acid-base balance:
Carbon dioxide tension is controlled by chemoreceptors in the medulla,
carotid body and aortic arch.
A rise in pCO2 levels or increase in acidity of CSF stimulates central alveolar
ventilation.
In respiratory failure the carbon dioxide buffering system in the haemoglobin
is overwhelmed leading to acidosis. The kidney, therefore, excretes an
increased chloride load using NH++ a weak cation to maintain ECF
osmolality. Metabolic acid is buffered by increased alveolar ventilation and
extracellular weak acids (plasma proteins, phosphate, bicarbonate) -
compensatory alkalosis. The coupling of bicarbonate and H2O leads to
formation of carbon dioxide resulting in increased alveolar ventilation and
excretion of carbon dioxide through the lungs.
In metabolic acidosis chloride is preferentially excreted by the kidneys. In
metabolic alkalosis chloride is retained, sodium and potassium are excreted.
Base Deficit/Excess (BDE):
Blood buffer base; sum of concentration of bicarbonate and non-volatile buffer
ions (serum albumin, phosphate and haemoglobin). Blood buffer base is
equal to the electrical charge difference between strong (fully dissociated)
ions.
BB= [Na+] + [K+] [Cl-]
BB level rises in metabolic alkalosis and falls in metabolic acidosis.
Base excess; amount of strong acid or base required to return the pH of 1 litre
of whole blood ( or serum-standardised base excess SBE) to 7.4, assuming a
pCo2 of 40mmHg and temperature 38 C.
In Acute Respiratory Acidosis or Alkalosis BDE does not change
In acute metabolic acidosis magnitude of change of pCo2 (mmHg) is the
same as that of the BDE (mEq/L)
Change in BDE represents the overall sum total of all acidifying and
alkanising effects.
Major limitations of the base-deficit approach;
unable to separate a hyperchloraemic metabolic acidosis from that associated
with unmeasured anions
Assumes normal levels of serum proteins, rare in critical illness.
Anion Gap:
The sum of the difference in charge of the common extracellular ions reveals
an unaccounted for gapof -12 to -16 mEq/L
Anion gap= [Na+]- [ Cl- + HCO3-] Normal is 8-12 mmol
It is used to distinguish metabolic acidosis due to bicarbonate loss (anion gap
Normal) from that of lactic acidosis where anion gap is increased.
Anion gap of more than 15 indicates accumulation of an organic acid anion in
plasma. Almost always means metabolic acidosis.
5 conditions that cause acid gain with anion gap are potentially fatal and must
be recognised.
Differential Diagnosis of Metabolic Acidosis by Anion Gap:
Normal AG Increased AG
Diarrhoea or other GI losses Lactic Acidosis
67
Renal Failure Ketoacidosis
Renal Tubular Acidosis Methanol poisoning
Expansion Acidosis Ethylene glycol poisoning
ASA poisoning
Acid Base Disturbances:
Body maintains normal pH through buffer systems, lung ventilation and renal
system. pH may be normal in abnormal situations of acid base abnormalities.
(i). Acute respiratory acidosis:
Respiratory acidosis is a primary rise in pCo2 with a compensatory rise in
plasma [HCO3-].
Increased pCo2 occurs in clinical situations in which decreased alveolar
ventilation occurs.
Differential diagnosis
Neuromuscular abnormalities with ventilatory failure
Central nervous system.
Airway obstruction.
a). chronic (COPD)
b). acute (asthma)
c). upper airway abstruction
d). obstructive sleep apnea.
4. Obstructive pulmonary disorders.
a). bony thoracic cage; flail chest, kyphoscoliosis.
b). parenchymal lesions; pneumothorax, pulmonary oedema.
c). large pleural effusions.
d). scleroderma
e). marked obesity (picwickian syndrome)
Rapid shallow breathing (increased dead space ventilation).
Treatment
Improve ventilation; intubate and ventilate. Increase ventilator rate. Reverse
narcotic sedation with Narloxone etc
(ii). Acute respiratory alkalosis:
Respiratory alkalosis is a primary fall in pCo2 with a compensatory decrease
in plasm [HCO3-].
Respiratory alkalosis occurs with increased alveolar ventilation.
Differential diagnosis
Central stimulation.
anxiety, hyperventilation syndrome, pain.
Head trauma or CVA with central neurogenic hyperventilation
Tumours
Salicylate overdose
Fever, early sepsis
Peripheral stimulation
pulmonary embolism
congestive heart failure (mild)
interstitial lung disease
pneumonia
altitude
68
hypoxaemia
Miscellaneous
hepatic insufficiency
pregnancy
progesterone
hyperthyroidism
iatrogenic mechanical overventilation
Treatment
Correct the underlying disorder
Hyperventilation syndrome; best treated by having the patient re-breath into a
paper bag to increase pCo2, decrease ventilator rate.
May accompany acute metabolic acidosis;
The reduction on pCo2 from the base line (40mmHg) is equal to the
magnitude of the base deficit, e.g. a patient with a lactate of 10mEq/L will
have a base deficit of -10 and a pCo2 of 30 mmHg. A pCo2 that is higher
than expected indicates a problem with respiratory apparatus. This may be
seen in a trauma patient with lactic acidosis secondary to mass blood loss
and a flail chest causing respiratory acidosis.
(iii). Acute Metabolic Acidosis.
An increase in acid in body fluids, reflected by a decrease in [HCO3-] and a
compensatory decrease in pCO2.
Results from alteration of strong ion difference.
Strong ion difference (SID) is altered when the relative quantity of strong
anions to strong cations changes. This can be caused by anion gain as
occurs with lactic-, renal-, keto- and hyperchloraemic acidosis or cation loss
as occurs with severe diarrhea or renal tubular acidosis.
Investigate for
(i). Lactic acidosis; serum lactate should mirror the magnitude of base deficit.
(ii). Dibetic ketoacidosis; look for hyperglycaemia with positive urinary
ketones.
(iii). Acute renal failure; Look for high serum urea and creatinine, low total
carbon dioxide. Diagnosis of exclusion.
Administration of intravenous fluids to patients has significant impact on acid
base balance. There are changes in free water volume and SID. Dilutional
acidosis results from administration of pure water to extracellular fluid (which
is alkaline). This can occur with administration of any fluid whose SID is 0 e.g.
5% Dextrose, 0.9% Saline (154 mEq of both Na+ and cl-) or other hypotonic
saline infusions. Dilutional acidosis thus results from a reduction in serum
sodium or an increase in chloride relative to sodium (hyperchloraemic
acidosis). Substitute with Ringers lactate.
Effects of metabolic acidosis;
(i). depression of myocardial contractility lowers cardiac output and tissue
perfusion.
(ii). Activates membrane calcium channels and inhibits release of
norepinephrine from sympathetic nerves. This leads to vasodilatation and
maldistribution of blood flow.
69
(iii). Increase in post-op nausea and vomiting. Seen during surgery when
large volumes of 0.9% saline are given.
Effect of hyperchloraemia;
plasma chloride levels affect afferent arteriolar tone through calcium activated
chloride channels and modulate release of rennin. This reduces renal blood
flow and glomerular filtration rate and reduces splanchnic blood flow.
Treatment of Metabolic Acidosis
Correct any underlying disorders ( eg diarrhoea etc)
Treatment with bicarbonate should be reserved for severe metabolic gap
acidosis. If the pH is < 7.20 correct with Sodium Bicarbonate. The total
replacement dose of bicarbonate can be calculated as follows
[HCO3-] needed in mEq = Base deficit mEq x patients weight in Kg
4
Replace with one half the total amount of bicarbonate over 8-12 hours and re-
evaluate. Be aware of sodium and volume overload during replacement.
Normal or isotonic bicarbonate drip is made with 3 ampoules of NaHCO3
(50 Mmol NaHCO3/ampoule) in 1L 5% Dextrose
(iv). Acute metabolic alkalosis.
Represents an increase in [HCO3-] with a compensatory rise in pCO2.
Differential diagnosis.
In two basic categories of diseases the kidney retains bicarbonate.
They can be differentiated in terms of response to treatment with sodium
chlori de and also by the level of urinary chloride as determined by ordering a
spot or randolm urinalysis for chloride.
Urine Chloride
<10 mEq /L >10 mEq/L
(Chloride responsive) (Chloride resistant)
Renal loss of chloride GI loss of H+, Cl- Excess mineralocorticoid
1. diuresis 1. NG suctioning 1.adrenal
2. miscellaneous 2. vomiting a. cushings
syndrome
(Cystic fibrosis) 3. chloride wasting b. hyperaldosteronism
3. post-hypercapnia dirrheah (Conns syndrome)
a. congenital 2. exogenous steroid
in children administration
b. villous adenoma 3. Bartters syndrome
Chloride-sensitive (responsive) Metabolic Alkalosis:

The initial problem is a sustained loss of chloride out of proportion to the loss
of sodium (either by renal or GIT).
This chloride depletion results in renal sodium conservation leading to a
corresponding re-absorption of [HCO3-] by the kidney.
In this category of metabolic alkalosis the urinary [Cl-] is <10 mEq/L
The disorder responds to treatment with intravenous NaCl.
Chloride-insensitive (resistant) Metabolic Alkalosis:
The pathogenesis is direct stimulation of the kidneys to retain bicarbonate
irrespective of electrolyte intake or losses.
70
The urinary [Cl-] >10 mEq/L and these disorders do not respond to NaCl
administration.
Treatment of Metabolic Alkalosis.
Correct the underlying disorder.
Chloride responsive;
replace volume with sodium chloride if depleted
correct hypokalaemia if present
NH4Cl and HCL should be reserved for extreme cases.
Chloride resistant;
Treat underlying problem such as stopping exogenous steroids.
Peri-operative metabolic alkalosis: Usually iatrogenic. Hyperventilation of
patients with chronic respiratory failure results in acute metabolic alkalosis
due to chronic compensatory alkalosis associated with chloride loss in urine.
Associated with an increase in SID due to sodium gain from administration of
fluids in which sodium is buffered by weak ions, citrate, acetate and
bicarbonate.
Critically ill patients are vulnerable to significant changes to SID and free
water. They have hypoalbuminemia that contributes to metabolic alkalosis,
chloride loss due to nasogastric suction, sodium and potassium loss due to
diarrhoea, surgical drains, fever and vomiting (leads to large volumes of
insensible loss and contraction alkalosis). Loop diuretics and polyuric renal
failure also leads to contraction alkalosis due to loss of chloride and free
water. Drug infusions play a significant role because they are diluted in
sodium rich solutions or administered in large volumes of free water.
Treating Acid Base Disturbances.
Lactic acidosis; volume resuscitation and source control
Diabetic ketoacidosis; volume resuscitation and insulin
Renal acidosis; dialysis
NB Use of Sodium bicarbonate is no longer emphasised. Causes i). volume
expansion. 7.5% solution is hypertonic. May improve cardiovascular
performance. ii). Increases SID due to administration of sodium without
accompanying strong anion. iii). Increased carbon dioxide generation. iv).
Induces intracellular acidosis.
Dilutional acidosis; Treated by increasing SID of infused fluids e.g. sodium
without chloride. Dilute 7.5% sodium bicarbonate into 1 litre of 5% dextrose or
pure water or use sodium acetate. Run as maintenance fluid (the SID is 144)
until the base deficit returns to zero.
Potassium.
Normal potassium homeostasis; shift into and out of cells. Excretion regulated
by kidney.
Normal potassium balance; ECF 3.5-5.5 (2%) ICF 140 mM (98%)
Daily intake 30-80 mmols (fruits and vegetables)
NB one large potassium meal = total ECF potassium.
Insulin promotes potassium uptake by cells.
Rise in plasma potassium concentration stimulates aldosterone. Aldosterone
stimulates potassium secretion and excretion.
K+ shift
71
K+ ions shift into cells in response to
i). insulin
ii). Catecholamines (B 2 receptors) e.g ventolin
iii). Anabolic state (growth, re-feeding etc)
K+ shift out of cells during
i). insulin deficiency-diabetes, fasting
ii). Cell ischaemia, necrosis (e.g rhabdomyolysis), red cell lysis, e.t.c
K+ excretion by kidney;
i). Regulated by cortical collecting duct
ii). Aldosterone stimulates sodium reabsorption.
iii). Makes lumen negatively charged
iv). Negative charge attracts potassium from cell
v). Aldosterone and plasma potassium set lumen K concentration.
vi). Flow rate also very important (volume) since excretion=
concentration x flow
vii). Flow depends on GFR, volume state.
Hyperkalaemia:
i). cardiac effect.
Life threatening arrhythmias when potassium concentration >
7mmM
Abnormal ECG when plasma K > 6
Peaked T waves
Broad QRS
Flat p waves
Sine wave
ii). Role of kidney
Always impaired potassium excretion is cause of hyperkalemia
due to
i). Low flow to CCD as a result of advanced renal failure,
severe extracellular fluid volume depletion, oliguria/anuria
ii). Low aldosterone activity as a result of adrenal insufficiency
(mineralocorticoid), impaired rennin secretion or AII
generation
Drugs promoting hyperkalaemia:
i). Block aldosterone generation by Angiotensin II; ACE
inhibitors, angiotensin receptor blockers.
ii). Block aldosterone action on CCD; spironolactone,
amiloride, triamterene.
iii). Multiple effects. Cyclosporine
Management of hyperkalaemia:
Urgent; for > 7, arrhythmias, or ECG changes. 1 amp calcium
gluconate Bolus, 20 U insulin bolus (in 1 amp 50% DW), 2-4
puffs ventolin or ventolin inhaler
Semi-urgent; increase urine flow-saline if appropriate,
furosemide, haemodialysis.
Hypokalaemia:
72
Cardiac, muscle weakness, metabolic alkalosis, impaired insulin secretion.
Hypokalaemia may be due to shift into cells (insulin, high catecholamines),
increased loss (GI-diarrhoea, vomiting, fistulas, colostomy; urine-diuretics,
polyuria, primary aldosteronism)
Treatment; oral KCl 8 or 20 mmol/tablet or liquid. IV- if urgent or unable to
take orally. 40mmol/l maximum concentration. 40 mmol/hr maximum rate.
Most hypokalaemic patients have high losses and volume depletion; in
monitored setting can give by central line boluses 40/100 mL if volume is a
concern.
73
CHAPTER 9
INCISIONS. WOUND CLOSURE. DIATHERMY. LASER. SUTURES

LIGATURE MATERIALS.
Introduction. The major goals when planning a surgical incision are to re-
establish functional soft tissue structural support and to give the most natural
aesthetic appearance with minimal distortion after healing has occurred. The
goals of wound closure include approximation and eversion of the epithelial
portion of the closure, obliteration of dead space, even distribution of tension
along deep suture lines, maintenance of tensile strength across the wound
until tissue tensile strength is adequate. Methods for mechanical wound
closure include staples, tape, adhesive, and sutures. Tissues are held in
proximity until enough healing occurs to withstand stress without mechanical
support. Suture material is a foreign body implanted in human tissues and will
elicit foreign body tissue reaction. During wound closure, a sterile field and
meticulous aseptic technique is important to minimize the risk of wound
infection. Other complications of wound healing such as hypertrophic scars,
wound dehiscence, may result from patient factors ( e.g.nutritional status),
incorrect suture selection, or technique that results in excessive tension
across the wound. Knowledge of the physical characteristics and properties of
suture and needle are important in skilful wound closure.
Inflammation and wound healing.
(a) Vascular response. Initial vasoconstriction as a direct response to trauma.
Activation of coagulation and complement cascades. Clot formation as a
result of platelet adhesion and aggregation. Degranulation of platelets
releases growth factors and chemotactic factors. The release of histamine
and 5HT causes vasodilatation, increased capillary permeability, and
margination of neutrophils.
(b) Cellular response. There is migration of neutrophils, macrophages and
lymphocytes. Macrophages produce growth factors leading to migration of
fibroblast and epithelial cells (e.g. platelet derived growth factor, PDGF,
insulin like growth factor, IGF-1, epidermal growth factor, EGF, transforming
groth factor, TGFb). This cellular proliferation results in epithelialisation,
contraction and fibroplasia formation in the wound to create an epithelial
barrier that is important in preventing infection and maintenance of fluid and
electrolyte balance. This is achieved through migration and proliferation of
epithelial cells at the site of granulation tissue formation. When epithelial
cover is complete epithelial growth stops through contact inhibition and
contraction of the wound, initiated by myofibroblasts in the granulation tissue,
takes place. Fibroblasts produce procollagen that leads to fibroplasia,
formation of collagen fibers with fibronectin and glycosaminoaglycans. They
regulate collagen synthesis, cellular differentiation and angiogenesis.
Maximum collagen production occurs at 20 days. There is remodeling and
contraction with 80% reduction in wound size and reduction of vascularity
and cellularity with maximum wound strength being attained at 3-6 months.
74
Factors influencing wound healing
(a) systemic factors. Age, sex, nutrition, vitamin and trace elements
deficiencies (vitamin C, vitamin A, zinc), drugs ( steroids, chemotherapy,
immunosuppression), systemic disease (diabetes, jaundice, malignancy),
hypoxia.
(b) local factors. Blood supply, infection, foreign bodies, surgical technique.
Scar formation.
Factors influencing scar formation;
a. individual genetic makeup
b. race
c. anatomical site
d. wound tension
e. age
f. placement of incision
g. surgical technique
To minimize the degree of post-operative scarring
-incision should run along Langers lines
-the finest suture possible should be used.
-tension should be avoided
-sutures should be removed as soon as possible
-traumatic wounds should be clean and edges excised
-exposure to sunlight should be avoided in the early postoperative period.
Scars healing with complications;
-contractures. Result if scars shorten. Seen in badly aligned scars not
corresponding to Langers lines. Can reduce joint mobility. May require z-
plasty or skin graft.
depressed scars. Result if skin becomes attached to deep tissue. Can be
treated by the release of normal skin from the margins of scar. This allows
de-epithelialisation of the scar and closure of skin edges over the top.
keloid and hypertrophic scars. All scars become hyperaemic and thickened
during the normal healing process. After several months, maturation results in
flattening of the wound. In some scars there is excessive collagen formation
that results in an elevated and red scar. If confined to the wound it becomes a
hypertrophic scar. If it extends beyond the wound into normal tissue it
becomes a keloid scar. Commonly seen in Africans especially in the
presternal and deltoid areas. Treatment may include intralesional steroid
injections, elastic compression dressing, silastic gel therapy, excision and
radiotherapy, laser therapy.
Diathermy.
Use of high frequency electric current to produce heat. Used to either cut or
destroy tissue or to produce coagulation. Electrical frequency used by
diathermy is 300kHz-3MHz (mains electricity is 50Hz). Patients body forms
part of the electoral circuit. Current has no effect on muscles. Effects of
diathermy depend on the current intensity and wave form used. Coagulation
is produced by interrupted pulses of current (square wave form). Cutting is
produced by continuous current (sinus wave form). Risk and complications;
75
can interfere with pacemaker function, arcing can occur with metal
instruments and implants, superficial burns may occur if spirit based skin
preparation is done, diathermy burns if plate is improperly applied.
Monopolar diathermy.
Electrical plate is placed on patient and acts as indifferent electrode. Current
passes between instrument and indifferent electrode. Localised heating is
produced at tip of instrument.
Bipolar.
Two electrodes are combined in the instrument (forceps). Current passes
between tips and not through patient.
Lasers.
Due to light amplification by the stimulated emission of radiation. Laser
emissions are collimated (parallel output beam results in little energy loss),
coherent ( waves are all in phase resulting in little energy loss) and
monochromic (all of the same wavelength). Effects of laser depend on
photochemical, photomechanical and photothermal effects. Tissue
penetration increases with wavelength. Pulsing of output can reduce thermal
damage.
Laser safety; Lasers are classified according to the amount of damage they
can cause into class 1 ( generally safe), class 2 (safe within the time of the
blink reflex), class 3 (cause blindness after short exposure from mirrored
surfaces), class 4 (unsafe even with reflection from non-mirrored surfaces). All
medical lasers belong to class 4 therefore both patient and operator must
wear goggles.
Risks associated with lasers. To patient; excessive burning, scar formation,
visceral perforation. To operator; accidental skin exposure.
Surgical drains.
Drains are inserted to evacuate established collections of pus, blood or other
fluids and also to drain potential collections. Their use is contentious.
Arguments for their use; drainage of fluid removes potential source of
infection, drains guard against further fluid collections, they allow early
detection of anastomotic leaks or haemorrhage, they leave a tract for potential
collections to drain following removal. Arguments against their use; presence
of a drain increases the risk of infection, damage may be caused by
mechanical pressure or suction, may induce an anastomotic leak, most
abdominal drains are ineffective after 24 hours.
Types of drains; open or closed, active or passive. Usually made from inert
silastic material. Induce minimal tissue reaction. Red rubber drains induce an
intense tissue reaction allowing a tract to form and this may be useful in some
situations e.g. biliary t-tube. Open drains; corrugated rubber or plastic sheets,
drain fluid collects in gauze pad or stoma bag, increases risk of infection.
Closed drains; consist of tube draining into a bag or bottle, chest and
abdominal drains, risk of infection is reduced. Active drains; mainatained
under suction, low or high pressure. Passive drains; no suction, function by
differential pressure between body cavities and the exterior.
76
Nasogastric tubes. Following abdominal surgery gastrointestinal motility is
reduced for a variable period of time. Gastrointestinal secretions accumulate
in stoma and proximal small bowel. This may cause post-operative distention,
vomiting and aspiration pneumonia. Nasogastric tubes may increase the risk
of pulmonary complications. May be left on free drainage or aspirated every 4
hours. Removed when volume of gastric aspirate is reduced.
Urinary catheters. Commonly used to alleviate or prevent urinary retention
and to monitor urinary output. Can be inserted transurethrally or
supapubically. Catheters vary by the material from which they are made
(latex, plastic, silastic, Teflon-coated), the length of the catheter (38 cm-male,
22 cm-female), the diameter of the catheter (10 Fr-24 Fr), the number of
channels (two or three), the size of the balloon (5 ml-30 ml), the shape of the
tip. Types; Foley, Gibbon, Nelaton, Tiemann, Malecot. Complications;
paraphimosis, blockage, by-passing, infection, failure of balloon to deflate,
urethral strictures. Precautions; choose an appropriate size catheter, insert
using an aseptic technique without force, do not inflate balloon until urine
comes out from the catheter, record the residual urine volume, learn how to
use catheter introducer, consider suprapubic if difficulty arises, remove at the
earliest possibility.
Sutures and needles.

Ideal suture characteristics; sterile, all-purpose can be used in any surgical
procedure, causes minimal tissue injury or tissue reaction, easy to handle,
holds securely when knotted, high tensile strength, favourable absorption
profile, resistant to infection. Difficult to achieve all these objectives.
Essential suture characteristics; sterility, uniform diameter and size, pliability
for eases of handling and knot security, uniform tensile strength by suture
type and size, freedom from irritants or impurities that would elicit tissue
reaction.
Suture size. 3 classes of sutures; collagen, synthetis absorbable and
nonabsorbable. Size refers to the diameter of the suture strand and is
deneted as zeroes. The more zeroes characterizing a suture size the smaller
the resultant strand diameter. The smaller the suture the less tensile strength
of the strand.
Natural sutures. Can be made of collagen from intestines of animals or from
synthetic collagen (polymers). Associated with tissue reaction.
Monofilament versus multifilament; Monofilament suture is made of a single
strand. More resistant to harboring microorganisms and ties more easily.
Multifilament is several filaments twisted or braided together. Les stif but
higher coefficient of friction. Greater tensile strength. Handles and ties well.
Increased capillarity may act as tract for introduction of pathogens.
Aborbable versus nonabsorbable sutures; Absorbable sutures provide
temporary wound support until the wound heals well enough to withstand
normal stress. Absorption occurs by enzymatic degradation in natural
materials and by hydrolysis in synthetic materials. Hydrolysis causes less
tissue reaction than enzymatic degradation. Non absorbable sutures elicit a
tissue reaction that results in encapsulation of the suture material by
77
fibroblasts. Commonly used in percutaneous skin closure and are removed
after sufficient healing has occurred at about 6-8 days. When used internally
they become permanently encapsulated in tissue.
Types;
class 1 (silk or synthetic fibers of monofilament, twisted or braided),
class 2 (cotton or linen fibers or coated natural or synthetic fibers-coating
causes suture thickness without adding strength),
class 3 ( metal wire of monofilament or multifilament).
Absorbable sutures. Natural; collagen (from submucosa of sheep intestine or
serosa of beef intestine). Surgical gut, plain ( tensile strength is maintained for
7-10 days. Absorption is complete within 70 days. Used for repairing rapidly
healing tissues that require minimal support, ligating superficial blood vessels,
suturing subcutaneous fatty tissue). Surgical gut, fast-absorbing (indicated for
epidermal use. Lasts 5-7 days). Surgical gut, chromic (treated with chromium
salt. Tensile strength is maintained for 10-14 days. Absorption rate is slowed
by chromium salt-90 days. May be used in the presence of infection).
Synthetic: chemical polymers. Absorbed by hydrolysis. Less tissue reaction.
Polyglactin 910-vicryl (braided multifilament suture coated with a copolymer of
lactide and glycolide. The water repelling qualities of lactide slows loss of
tensile strength and the bulkiness of lactide leads to rapid absorptionof suture
mass once tensile strength is lost. Also coated with calcium stearate which
permits easy tissue passage, precise knot placement and smooth tie down.
Tensile strength is 65% at 14 days posimplantation. Absorption is minimal for
40 days and complete in 50-70 days. Cause minimal tissue reaction. May be
used in the presence of infection. Used in general soft tissue approximation
and vessel ligation. Other similar-Dexon II).
Nonabsorbable sutures. Natural; surgical silk. Surgical cotton. Surgical steel.
Synthetic; Nylon. Plyester fiber( Dacron-uncoated, Ethibond-coated).
Polypropylene (prolene).
Suture selection; depends on surgeon training and preference.
Ideal surgical needle characteristics. High quality stainless steel, smallest
diameter possible, stable in the grasp of the needle holder, capable of
implanting suture material through tissue with minimal trauma, sharp enough
to penetrate tissue with minimal resistance, sterile and corrosion resistant to
prevent introduction of microorganisms or foreign materials into the wound.
Point; portion of the needle from the tip to the maximum cross section of the
body. Body; majority of the needle length. Interacts with needle holder.
Swage; suture attachment end. Creates a single continous unit of suture and
needle.
Point types; Cutting (conventional, reverse, side-cutting). Taper-point (round
needle). Blunt point.
Body types; Straight. Half-curved. Curved. Compound curved.
Needle selection; Main consideration is to minimize trauma. Taper needle is
sufficient for tissues that are easy to penetrate. Cutting needles are reserved
for tough tissues-skin. Needle body diameter usually matches the suture size.
78
CHAPTER 10
POSTOPERATIVE COMPLICATIONS
Specific complications often occur at certain times after operation

The following time scales should be regarded as a guide and not absolute
rules
First 24 hours;
hyperpyrexia
Systemic response trauma
Pre-existing infection
24 to 72 hours:
Pulmonary atelectasis
Chest infection
3 to 7 days:
Chest infection
Wound infection
Intraperitoneal sepsis
Urinary tract infection
Anastomotic leak
7 to 10 days:
Deep venous thrombosis
Pulmonary embolus
The basic mechanisms leading to atelectasis are:

Increased volume of bronchial secretions
Increased viscosity of secretions
Reduced tidal volume and ability to cough
Clinical features
Postoperative pyrexia - usually presenting at about 48 hours
Often accompanied by tachycardia and tachypnoea
Examination shows reduced air entry, dullness on percussion and reduced
breath sounds
X-ray shows consolidation and collapse
Treatment
Intensive chest physiotherapy
Nebulised bronchodilators
Antibiotics for associated infection
Pneumonia
Nosocomial pneumonia occurs in 1% of all patients admitted to hospital
Occurs in 15-20% of unventilated ICU patients
Occurs in 40-60% of ventilated ICU patients
79
Organisms involved include
Gram-negative bacteria (Pseudomonas aeruginosa, Enterobacter)
Staph. aureus
Anaerobes
Haemophilus influenzae
No evidence that prophylactic antibiotics reduce the risk of pneumonia
Aspiration pneumonitis
Aspiration of gastric contents results in a chemical pneumonitis
Most commonly seen in apical segments of right lower lobe
If unrecognised or inadequately treated it can result in a secondary bacterial
infection
Secondary infection is usually with gram-negative and anaerobic organisms
Treatment
Tilt table head down and suck out pharynx
Consider intubation and endotracheal suction
Prophylactic antibiotics should be given
No evidence that steroids reduce inflammatory response
Wound dehiscence
Affects about 2% of mid-line laparotomy wounds
Serious complication with a mortality of up to 30%
Due to failure of wound closure technique
Broken sutures or slipped knots
Inadequate muscle bites
Usually occurs between 7 and 10 days post operatively
Often heralded by serosanguinous discharge from wound
Should be assumed that the defect involves the whole of the wound
Management
Opiate analgesia
Sterile dressing to wound
Fluid resuscitation
Early return to theatre
Resuture under general anaesthesia
Exact technique is variable
Interrupted or mass closure with non-absorbable sutures often used
The use of 'deep tension' sutures is controversial
Believed by some to strangulate muscle and weaken the closure
Also painful and associated with increased risk of infection
80
CHAPTER 11
SURGICAL INFECTIONS AND THEIR MANAGEMENT
Aims:
Define the terminology associated with infection.
Describe the preoperative, intraoperative and postoperative factors that can
lead to infection
Detail the signs, symptoms and investigation of surgical infection
Discuss which pathogens are likely to cause infection
Provide a rationale for antibiotic prescription, whether as prophylaxis or after
established infection (either before or after microbiological diagnosis)
Objectives:
Identify patients at risk of perioperative surgical infection
Recognise and investigate the presence of infection in patients
Make an educated guess as to which organisms are causing infection
Treat the systemic manifestations of infection
Formulate a rationale for blind antibiotic therapy.
Introduction
Perioperative infection of the surgical patient is common. Lifestyle factors,
such as diet and smoking, together with the presenting disease process (e.g.
cancer), predispose patients to infection. Endogenous microbial colonisation
of tissues can occur as a consequence of the course of a disease (e.g.
perforation of an intra-abdominal viscus) or as a result of operative
intervention. Exogenous infection of the patient may occur through non-sterile
surgical technique or simply by failure to maintain an acceptable standard of
cleanliness on wards or between each patient contact. The prevention of
infection is of paramount importance and may be achieved by
antiseptic/aseptic precautions, together with the judicious use of prophylactic
antibiotics. The management of established infection involves general
interventional care of the patient combined with antibiotic therapy.
Occasionally, a surgical procedure may be required. Communication with, and
the involvement of, microbiologists facilitate rational antibiotic therapy.
Indiscriminate use of antibiotics can lead to both microbial resistance and
superadded infection, resulting in increased mortality rates, particularly
amongst immunosuppressed patients.
Some definitions
There is often confusion amongst medical practitioners over what is meant by
the various terms used to describe infection and its systemic effects.
Currently, the most commonly accepted definitions are those formulated by
the American College of Chest Physicians and the Society of Critical Care
Medicine (1992).
Infection. Microbial phenomenon characterised by an inflammatory response
to the presence of microorganisms or the invasion of normally sterile host
tissue by those organisms.
81
Bacteraemia. The presence of viable bacteria in the blood.
Systemic inflammatory response syndrome (SIRS). The systemic
inflammatory response to a variety of severe inflammatory insults. The
response is manifested by two or more of the following conditions:
Temperature outside the range 36-38 0C
Heart rate above 90 beats per minute
Respiratory rate more than 20 breaths per minute, or PaCO2 lower than
4.3kPa.
White blood cell (WBC) count outside the range of 4 - 12 x 109 per litre, or
more than 10% immature forms
Sepsis. The systemic inflammatory response caused by infection i.e. the
presence of the above physiological parameters in response to the presence
of an identifiable infective agent.
Severe sepsis. Sepsis associated with organ dysfunction, hypoperfusion or
hypotension. Hypoperfusion and perfusion abnormalities may include, but are
not limited to lactic acidosis, oliguria, or an acute alteration in mental status.
Hypotension describes a systolic BP of less than 90 mmHg or a reduction of
more than 40 mmHg from baseline, in the absence of other causes for
hypotension.
Septic shock. Sepsis with hypotension, despite adequate fluid resuscitation,
along with perfusion abnormalities that may include, but are not limited to
lactic acidosis, oliguria, or an acute alteration in mental status. Patients who
are on inotropic or vasopressor agents may not be hypotensive at the time
that perfusion abnormalities are measured.
Multiple organ dysfunction syndrome (MODS). Presence of altered organ
function in an acutely ill patient such that homeostasis cannot be maintained
without intervention.
Note that the above definitions describe a progression of worsening disease
from infection to MODS. Septicaemia, which inaccurately describes a wide
range of infection and its pathophysiological consequences, has been
abandoned in the terminology of infection.
In addition, several other definitions are used;
Table 20. Definitions associated with surgical infection
Carrier A person who has been colonised, but who does not manifest infection
Pathogen An agent with the ability to cause infection
Endogenous infection Infection of the body by natural host flora
Exogenous infection Infection of the body by organisms not usually cultured from the host
Nosocomial infection Infection acquired during hospitalisation
Virulence The potential of a pathogen to cause infection
The pathophysiology of infection

Many pathogens normally reside in or on the human body without causing
infection. For example, 35% of family members of patients with Neisseria
meningitidis infection (meningococcal meningitis) have been found to be
asymptomatic carriers. It has been estimated that the adult human intestine
82
contains 2 kg of bacteria. In the non-diseased state a number of specific and
non-specific mechanisms contribute to the hosts resistance to infection.
Non-specific mechanisms of immunity
There are a number of physical barriers that prevent host inoculation by
pathogens. To gain entrance to the body, organisms must physically breach
membrane barriers in the host, including the skin, respiratory tract, mucous
membranes or urinary tract. In addition a number of non-specific host
defences operate (see table 2).
Table 21. Non-specific host defences.
Behavioural factors Personal hygiene, nutrition, personal contact

Skin Fatty acids, low pH
Tear production Tears contain antibacterial lysozyme and immunoglobulin A
Respiratory tract
upper Coughing and sneezing mucociliary escalator, bactericidal secretions, secretory IgA,
lower macrophages,
Gastrointestinal tract Stomach acidity, enzyme production, hepatic macrophages-Kuppfer cells, secretory IgA
Urinary Tract Urine flow, urine acidity
Normal surface flora Competiotion for nutrients produce antimicrobial agents
Specific mechanisms of immunity

Specific mechanisms of immunity are those that have developed either
artificially or naturally, through evolution. Artificial immunity may be provided
passively or actively. Passive immunity involves injection of immunoglobulin
or antiserum to provide immediate protection; immunity declines over the
subsequent few months. Active immunity (vaccination) employs inactivated or
attenuated organisms (or structural elements thereof) to induce the formation
of antibody isotypes. A low intensity, short duration phase of antibody
formation occurs during the month after vaccination. Subsequent exposure to
the appropriate pathogen produces a rapid (3-5 days), larger and more
sustained response to the infecting organism.
Similarly, natural immunity may be provided actively or passively. Passive
natural immunity occurs due to maternal transplacental transfer of antibodies
to the fetus and provides a degree of immunity for the newborn until 6 months
of age. Active natural immunity involves a complex interaction between
humoral (antibodies, complement), cell mediated (macrophages, T
lymphocytes and B lymphocytes) and cytokine components.
Table 3. Host response to infection.

Non specific mechanisms Specific mechanism-immunity
Physical barrier Artificial
Behaviour Active vaccination
Secretions Passive immunoglobulin antiserum
Natural flora
Natural
Active humoral, cell mediated
Passive maternal transfer of antibodies
83
Infection, therefore, is likely to result when the host responses described
above are bypassed, circumvented or absent, particularly by a more virulent
organism.
Direct inoculation of pathogens into the bloodstream avoids non-specific host
responses to infection. This may occur when barriers are absent or damaged:
de-epithelialisation; burns, trauma
gross tissue damage; burns, trauma, infection, surgery
medical intervention; intubation and ventilation, iatrogenic (intravenous
access, inadvertent tissue damage), drugs (eg H2 antagonists)
disease process; perforation intraabdominal viscus, inflammation
(pancreatitis, SIRS)
In addition, and less apparently, the structural and functional integrity of intact
barrier mechanisms may be indirectly disrupted:
alterations in antibiotic usage; natural flora, nosocomial colonisation,
malnutrition, use of bowel preparations
damage to immobility and pressure necrosis of tissues; epithelial cells
irradiation, chemotherapeutic cytotoxins, contact hypersensitivity (to
dressings, skin
preparations)
tissue ischaemia/anaemia; hypoxia, hypotension, reduction of arterial flow
internal emboli, external inflammation, cross clamping
Specific immunity may be compromised in several ways:
overwhelming infection after gross inoculation, genotypic factors,
immunosuppression cancer, malnutrition, drugs (immunosuppressants,
steroids), HIV infection, blood transfusion
There may exist considerable interindividual variation in response to
bacteraemia. A cohort of patients undergoing the same surgery under similar
conditions will exhibit a range of responses to surgical infection. Some
patients will not develop infection. Others will exhibit mild infective signs but
will recover. A minority may develop fulminant infection, leading to multiple
organ failure and death. Both a reduction in major histocompatibility complex
(MHC)-II expression by monocytes (which effect antigen recognition and
presentation) and an excess of CD16 expression on neutrophils have been
described in non survivors, implying that death after infection may occur as a
result of both an underactive and an overactive immune response.
Preoperative considerations
There are a number of preoperative factors that may predispose patients to
surgical infection. Their identification and treatment prior to surgery may
greatly contribute to a reduction in the rates of infection and perioperative
morbidity. Three groups of preoperative factors are recognised - coexisting
diseases, surgical diseases and environmental factors.
Coexisting conditions
This group comprises chronic pathologies or behaviour exhibited by the
patient prior to surgery.
Cardiovascular disease
Cardiovascular pathology may effect infection, inhibiting the bodys response
to infection or limiting the ability of the patient to cope with physiological strain
84
placed upon it by sepsis. Atherosclerosis, venous stasis and cardiac failure
give rise to tissue ischaemia, which may be compounded by anaemia.
Ischaemia may predispose to infection, inhibit humoral and cell mediated
immune responses and delay recovery from infection. Pulmonary oedema
attenuates non-specific lung immune responses. Damaged heart valves may
become colonised during episodes of bacteraemia, resulting in bacterial
endocarditis. During sepsis and MODS, ischaemic heart disease limits cardiac
output, which worsens tissue ischaemia.
Respiratory disease
Chest infection is common following surgery, with an increased incidence
amongst asthmatics and patients with chronic obstructive pulmonary disease
(COPD). Patients who have surgery whilst suffering from an upper respiratory
tract infection (or up to two weeks after the infection) have both an increased
risk of airway complications during anaesthesia (coughing, laryngospasm)
and postoperative chest infection; this is particularly true of children. Chest
infection results in relative hypoxia, which can worsen wound healing, and
may result in wound dehiscence after bouts of coughing.
Smoking
Smokers are at increased risk of perioperative surgical infection. Smoking is
an airway irritant. It results in inflammation, disruption of ciliary function and
increased production (with decreased clearance) of respiratory secretions.
Chronically, alveolar fibrosis and emphysematous damage occur, disrupting
immune and respiratory function. Carboxyhaemoglobin has 100 times greater
affinity than oxygen for haemoglobin, resulting in reduced oxygen transport by
haemoglobin. Ischaemia is worsened by smoke related increases in blood
viscosity (due to hypoxia induced polycythaemia) and cardiovascular disease
(atherosclerosis and coronary ischaemia). Immune function appears to be
inhibited by some of the 4000 chemicals that have been identified in cigarette
smoke together with lowered immunoglobulin levels and decreased leucocyte
function.
Preoperative cessation of smoking should be strongly encouraged, preferably
for more than 8 weeks before surgery. Carboxyhaemoglobin has a half-life of
4 hours; so even 24 hours cessation allows relative normalisation of
haemoglobin oxygen carriage.
Obesity
Several definitions of obesity exist, but the most commonly used describes a
person as obese if their body mass index (BMI) is more than 30.
Body mass index = weight (kilograms)/height (metres)2
The physiological stresses placed on the body by obesity lead to excessive

perioperative morbidity and mortality.
Perioperative infection is more common for several reasons:
1. The obese have increased chest wall weight and a greater volume of
intraabdominal contents. When placed supine, the compliance of their
chest wall decreases, causing the functional residual capacity (FRC-
the volume of air in the lungs after tidal expiration) to fall below the
85
closing capacity (the volume of air in the lungs when small airways
begin to close). This leads to small airway closure, atelectasis and
ventilation/perfusion mismatch, which is worsened by anaesthesia and
neuromuscular blockade. Being unable to cough as effectively as
thinner patients, they are therefore more prone to postoperative chest
infections. In addition, the obese are more prone to gastro-
oesophageal reflux, which may contribute to pulmonary colonisation by
enteric organisms.
2. The resultant hypoxaemia, together with the increased oxygen
consumption and ischaemic heart disease associated with obesity,
leads to relative tissue ischaemia and results in poor wound healing,
with dehiscence and infection.
3. suture lines are placed under abnormal strain in obese people resulting
in wound dehiscence.
4. Diabetes and abnormal glucose tolerance are more common in the
obese and are worsened by the stress response to surgery, resulting in
poor wound healing and urinary tract infection.
5. pressure sores are more common. Hyperglycaemia and hypoxia play a
role, but ischaemia due to body size is of primary importance.
6. deeper skin folds produce warm, humid conditions for bacterial growth
and facilitate bacterial entry to the body through friction damaged skin.
Malnutrition
In the Western world, malnutrition is an often under-recognised condition in
patients presenting for surgery. The patient may be undernourished (a pure
calorie deficiency) or inappropriately nourished (e.g. obtaining virtually all their
calories through the intake of alcohol!). Several groups of patients are at
greater risk of malnutrition: babies, the elderly, starved patients, alcoholics
and patients with malabsorption, intestinal fistulae, chronic sepsis, previous GI
surgery, cancer (particularly if undergoing chemotherapy or radiotherapy) or
chronic liver disease. Hypercatabolism, associated with the stress response to
surgery, further reduces the nutritional reserves of the patient. Malnutrition
results in poor wound healing, increased muscle breakdown (predisposing the
patient to chest infection) and reduced immune function.
Liaison with dieticians is important. Nutritional support in the perioperative
period may be provided by supplemental use of nutritional drinks, nasoenteral
feeding or parenteral nutrition.
The elderly
Old age is not per se an independent variable for perioperative infection, but a
number of pathophysiological changes occur in the elderly that increase the
likelihood of infection:
reduced chest and lung compliance, raised closing capacity and reduced
autonomic responses to hypoventilation predispose to chest infection
atherosclerosis and reduced cardiac function lead to tissue ischaemia, with
delayed wound healing, which may be worsened by anaemia, increased
incidence of occult malignancy, obesity, malnutrition and increased
alcoholism, reduced mobility
reduced communication and reduced compliance with treatment
86
increased periodontal disease
thin skin
impaired temperature regulation
reduced immune function
Diabetes
In the perioperative period, several factors alter glycaemic control in the
diabetic patient, including fasting, anxiety and the stress response to surgery.
Diabetics are more prone to infection than non diabetics because:
cellular immunity is reduced
glycosuria and chronic renal failure predispose to urinary tract infection
peripheral neuropathy reduces patient awareness of early infection (e.g. loss
of pain sensation)
autonomic neuropathy reduces sensitivity to hypoxia and hypercapnia,
resulting in hypoventilation and reduced blood oxygen carriage. Autonomic
neuropathy also produces gastric paresis with an increased incidence of
aspiration pneumonia
Perioperative glycaemic control may be improved by the involvement of the
diabetic team, and by using sliding-scale short-acting insulin regimes, for
both insulin dependent and non-insulin dependent diabetics.
Steroids
Steroids, although invaluable in the treatment of autoimmune disease, organ
transplants and inflammatory disorders, have several side effects that
predispose patients to infection:
altered body habitus and obesity
thinning of the skin, increasing the likelihood of it being breached by minor
trauma (e.g. removal of adhesive bandages) and delaying wound healing
hyperglycaemia
reduced immune function
reduced fibroblast function, decreased fibrosis and decreased blood vessel
proliferation
Despite these problems, steroid usage should continue throughout the
perioperative period. Cessation may have two adverse effects. Firstly, the
condition for which the steroids are being given may worsen; this may not be
so problematic in the case of, for example, polymyalgia rheumatica, but can
lead to significant morbidity, for instance, if it enables rejection of a
transplanted organ. Secondly, chronic steroid administration causes adrenal
suppression. Perioperative cessation of steroids could therefore render the
patient less capable of dealing with the stress of surgery. Indeed, it may be
the case that those on exogenous steroids require perioperative
supplementation, particularly for more major surgery, because they are
unable to produce the endogenous steroid surge required to enable the body
to cope with trauma.
Surgical conditions
Certain surgical pathologies predispose to perioperative surgical infection.
Gastrointestinal disease
The alimentary canal, from mouth to anus, is colonised with bacteria.
Excessive translocation of bacteria from the gut lumen into the circulation or
87
to surrounding tissue can occur quickly if the structural and functional integrity
of the gut wall is breached, such as may occur with facial trauma, duodenal
and diverticular perforation, or mesenteric infarction. Spillage of large bowel
contents into the abdominal cavity bypasses the immune capacity of the liver,
and bacteria may translocate into the circulation in the subphrenic area and
paracolic gutters. Collection of blood, pancreatic secretions and bacteria can
result in abscess formation, particularly in the subphrenic region. This may be
prevented to a degree by thorough irrigation of the abdominal cavity, prior to
closure.
Trauma
Soft tissue injury causes haematoma formation, oedema and tissue
ischaemia, which provide ideal growth conditions for bacterial growth and
replication. Skin damage promotes wound colonisation. Deeper infections
may result due to blunt trauma and penetrating injury, particularly if
inoculation of debris (such as clothing, bullets, skin) occurs. Severe trauma
leads to massive endothelial damage, with the release of vasoactive
substances and inflammatory mediators, resulting in multiple organ failure;
sepsis is often coexistant (either secondary to the trauma itself or due to
enteric bacterial translocation) and mortality is high.
Burns
Burns cause thermal damage to tissue, which has two effects. Firstly, the
burnt tissue becomes ischaemic, due to blood vessel damage and oedema. A
serosanguinous exudate is produced by skin that is partially burnt which acts
as a growth medium for bacteria. Secondly, in a similar fashion to severe
trauma, the massive endothelial damage associated with burns effects an
inflammatory cascade that results in MOF. Large burns cause extreme
hypercatabolism so malnutrition quickly ensues, as does hyperglycaemia,
which both favour infection.
Environmental factors
Semmelweiss described asepsis in 1851. Lister described antisepsis in 1867.
Both recognised that disease could be transmitted from one person to
another; even if the carrier did not themselves show signs or symptoms of
disease. Scrupulous hygiene on wards and amongst staff was the main
method of infection control until the introduction of antibacterial agents
(notably penicillin in the early 1940s). Subsequent reliance on antibiotics to
treat infection has produced a degree of indifference to maintaining standards
of hygiene in hospitals. The recent evolution of multiply drug resistant
bacteria, however, has reiterated the importance of antiseptic precautions.
The hospital environment
By the nature of their activity, hospitals are prone to the transmission of
infection amongst patients. Intrapatient and interpatient infection may occur
through patient/patient, patient/relation and patient/staff contacts, as well as
through ventilation systems, washing and sanitary facilities. It is therefore
prudent to minimise patient contact with the hospital environment:
investigations and preoperative assessment may be carried out on an
outpatient basis and the time between admission and surgery should be
minimised. Patient transfer around the hospital and between hospitals should
88
be avoided. The importance of handwashing (and the use of alcohol and
glycerine skin lotion) by relatives and staff between patient contacts cannot be
underestimated and is to be strongly encouraged. Appropriate protective
clothing may be required to nurse some patients. Special areas or wards
should be reserved for patients with established infection or particularly
virulent forms of infection. Similarly, those patients at particular risk of
infection (those with HIV or haematological malignancy) should be isolated
onto special wards. An infection control team should be employed to
coordinate the hospitals infection policy.
The surgical list

The order of the surgical list may need to be altered to account for operations
or patients with a high risk of infection. Surgical procedures may be stratified
into 4 classes, according to their potential for causing both infection and
contamination of the surgical environment (table 4).
The theatre environment.
Theatre design and the conduct of surgery and staff have been designed to
minimise the likelihood of perioperative infection. These include:
List order
This is common sense and means putting a grossly infected patient on the
end of the list rather than the beginning.
Area designation
The theatre environment becomes progressively more sterile from the front
door to the operating table. The patient initially passes from the ward to
theatre reception, beyond which relatives should not be allowed to pass. From
reception, or a holding area, they pass to the anaesthetic room.
Accompanying ward staff should wear shoe coverings and hats during this
transfer, and should leave shortly after handing over the patient. All theatre
staff should wear surgical scrubs and theatre shoes, have their hair tied back
under theatre hats and avoid the wearing of make-up or jewellery. Staff
should never leave the theatre environment in surgical gear; if this is
unavoidable, they should always change their scrubs before returning to
theatre. Non-sterile non-surgical procedures, such as urinary catheterisation,
should be carried out in the anaesthetic room, prior to transfer to the operating
theatre. Likewise, blankets and extraneous items should be removed before
entering the operating theatre.
Operating theatre design
Operating theatres are ventilated with positive pressure, clean and filtered air
that cycles from the patient to the periphery of the theatre. For most types of
surgery, the air is recycled 20 times an hour. This may be increased to 40
times an hour in the case of prosthetic joint surgery, for which, specially
designed compartmental airflow systems may also be used. The design of
entrances and exits is such that laminar airflow is correctly maintained, even
when doors are opened. Three separate areas of the operating theatre exist:
the operating room proper and the instrument preparation room, both of which
are maintained highly sterile, and the scrub area. The operating theatre floor
should be cleaned with antiseptic solution between each case, and is more
89
thoroughly decontaminated and sterilised after each surgical list. Ideally, after
dirty cases a period of 30 minutes should elapse before commencing the
next case, to allow sufficient time for airborne pathogens to be filtered.
Separate areas external to the operating theatre are maintained for the
disposal of waste, the storage of equipment and the cleaning of equipment.
Scrubbing
Correct scrubbing technique is essential to maintain a sterile field around the
patient. The process should be taught and retaught to surgeons by theatre
sisters. The surgeon should wear clean theatre dress, a theatre cap and a
surgical mask. A gown pack is opened and surgical gloves placed, opened,
next to it. Before the first patient of the list, a five-minute handwash should be
performed, using Betadine or chlorhexidine. Nails should be scrubbed. The
hands are dried, and the gown is put on followed by the gloves. A second
person ties the surgeon into the gown. Between subsequent cases a two-
minute hand wash is sufficient, providing the surgeon has not left the theatre
environment in the interim, and has not just operated on a dirty case.
Regloving is required: if the gloves are punctured, if a non-sterile area/person
is touched, during long procedures, or during dirty procedures.
Table 4. Classes of surgical procedure.
Parameter Class I Class II Class III Class IV

GI. GU, Intact Transaction with Transaction Dead tissue,
tracheobronchial minor spilage with major direct infection,
system integrity spillage pus
Incision
through
infected tissue
Sterile technique Continuous Minor lapses Interrupted Contamination
despite sterile
technique
Antibiotic Not required Single dose Broad Broad spectrum
prophylaxis spectrum
Wound infection 1.5% <8% 12% >25%
rate 15-25%
without
antibiotics
Surgical wound Nontraumatic Mildly Grossly Contaminated
produced uninfected contaminated contaminated with pus, faeces
or extraneous
material
Examples Endocrine, Elective GI, GI perforation, Abscess, Faecal
Orthopaedics, Dental, Open fracture peritonitis,
Skin Gyaneecological reduction Trauma >4
hours
The patient
Ideally, the patient should be encouraged to shower before surgery. Shaving
of the incision site may be required, but should be performed carefully to
avoid microabrasions, which encourage infection. Once on the operating table
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(correctly positioned and prepared by the anaesthetist), the patients skin
should be cleaned with antiseptic solution. Betadine or chlorhexidine are
commonly used. Betadine should be applied for at least three minutes prior to
incision; it has the advantage over chlorhexidine of clearly demarcating the
area cleaned, but excites a higher incidence of allergic reactions. Cleaning
should advance from the proposed site of incision outwards. Drapes are
applied to leave the incision site exposed, but to cover every other part of the
patient, which might come into contact with sterile personnel or equipment.
Transparent, adhesive drapes are increasingly used to further limit patient
skin exposure.
Adequate care should be taken during the procedure to maintain tissue
perfusion and oxygenation. This is mainly the concern of the anaesthetist,
who should endeavour to keep the patient normovolaemic, normotensive and
normothermic, as well as protecting pressure points and reducing patient
stressors (e.g. awareness and pain).
Surgical technique.
The practice of surgery has become considerably more refined with the
passage of time. Speed is no longer the only requirement of a good surgeon.
Attention to intraoperative surgical technique can significantly hinder the
development of perioperative infection. The following factors should be
considered:
Attire, scrub technique, patient preparation.
Choice of technique. For instance, minimally invasive surgery reduces both
tissue contamination by skin flora and the degree of tissue trauma. The
infection of prosthetic material can be particularly disastrous; therefore,
avoidance of prosthetics by the use of autologous tissue may be beneficial.
Surgery of infected material. Adequate debridement of dead and infected
tissue is required, together with irrigation (hence the surgical maxim the
solution to pollution is dilution). Delayed primary closure or healing by
secondary intention may be indicated. More esoteric treatments may be
employed, including suction packing, hyperbaric oxygen therapy and the
application of maggots.
Haemostasis, closure and wound dressing. Haematomas provide an excellent
growth medium for bacteria, so attention should be given to attaining
haemostasis at surgery, particularly in patients with coagulopathy, cancer and
chronic infection. Expansion of a haematoma may further compromise tissue
blood supply. Drains may be used to prevent haematoma formation or the
accumulation of infected/infectable fluids, but should be removed shortly after
drainage of fluid ceases. Closure of the wound should aim to reconstitute
normal anatomy, so as to prevent the formation of tissue dead spaces, in
which seromata and bacterial multiplication might occur. Sutures should be
applied in such a way as not to compromise the blood supply of the wound
(thus avoiding wound breakdown). A range of suture material is available (e.g.
natural and synthetic sutures, staples, self adhesive sutures and tissue glue)
and the choice should be made according to the clinical indication. Sutures
are removed, if necessary, once the skin has united. Dressings should be
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clean and applied without compromising blood supply. Postoperatively,
dressings should be subject to regular inspection and replacement.
Diagnosis of infection
A number of clinical, haematological and microbiological variables may be
assessed in order to both diagnose and monitor the course of an infection.
Wound inspection.
Infected wounds may be red, swollen, tender and hot (rubor, tumor, dolor and
calor) due to the localised release of endogenous chemicals that cause
vasodilation, increased membrane permeability and pain fibre sensitisation.
The wound may extrude pus (which is predominantly composed of white
cells), and may be malodorous. In addition, there may be a degree of
dehiscence or tissue breakdown around drain sites. The efficacy of treatment
may be observed by daily inspection of the wound.
Temperature
The wound itself may be hot. The patient may have a raised core temperature
(above 37.50C), due to the systemic release of pyrogens, such as interleukin-
6, and the patient may be diaphoretic (sweaty) in an attempt to reduce their
body temperature. Hyperpyrexia may lead to rigors, confusion, lethargy and
tachycardia. Note that hyperpyrexia may occur in the perioperative phase
without the presence of infection (e.g. stress response, post blood transfusion,
drug reactions and malignancy), or due to an infection not associated with the
wound (e.g. urinary tract infection, chest infection and venous line related
sepsis. Swinging pyrexias are associated with abscess formation, low-grade
pyrexia with wound infection (particularly if they occur around 5 to 6 days after
surgery).
White cell count (WCC)
The WCC is most commonly raised in the presence of infection, with a
marked predominance of neutrophils on the differential count. However, note
that the white cell count may be either low or normal, particularly in
immunosuppressed patients, leukaemic patients or occasionally when Gram-
negative organisms infect the patient.
Other biochemical markers
C reactive protein (CRP- an acute phase protein) levels, erythrocyte
sedimentation rate (ESR) and plasma viscosity may all be increased in the
presence of infection. They are reasonably sensitive markers for infection but
are very non-specific, and their use therefore is limited to monitoring the
progress of treatment. CRP levels are mildly raised after surgery, decreasing
to normal after 48 hours. The ESR and plasma viscosity may be normal after
surgery depending on the degree of haemodilution.
Radiology
Radiological tests may be used as an adjunct to thorough clinical examination
and appropriate simple investigations. X rays may be used according to the
findings of the clinical examination (e.g. chest X-ray if a chest infection is
suspected). Ultrasound scans may be used to detect collections of pus,
though abdominal ultrasound is often technically difficult and may prove
inconclusive in the presence of excess bowel gas or fat. Computerised
92
tomography is an alternative to ultrasound scanning, but subjects the patient
to a high degree of radiation exposure. A white cell scan uses radiolabelled
white cells (indium 111-labelled leucocytes) to identify the site of infections
that are difficult to diagnose clinically (e.g. osteomyelitis and vascular graft
infection), although there is a real (but small) risk of HIV transmission with this
technique.
Microbiology
Microbiological analysis of tissue specimens does not so much confirm the
presence of infection as discover what the infecting organism is. Ideally, a
specimen of pus or infected tissue should be sent this may involve needle
aspiration or operative retrieval of the specimen. Other samples to consider
sending include blood, sputum, urine, faeces and drain contents. Samples
should be sent before the commencement of antibiotic therapy. If the patient
is already taking antibiotics, the type, dose and length of treatment should be
written on the request form. Samples should be collected in a sterile manner
to avoid false positive results due to cross contamination. Blood should be
sent for microbiology, culture and sensitivities if the patient is systemically
unwell. Blood should be taken in the normal sterile manner; an alcoholic swab
should be used to clean the top of the culture bottles, the aerobic bottle being
filled first, to avoid the inadvertent introduction of air into the anaerobic bottle.
The results of a Gram stain are available within a few hours. Culture and
sensitivity results take 24-72 hours. Immunological methods (for viruses) and
more elaborate culture methods (e.g. for fungi and tuberculosis) may take
longer.
Species of Spirochaetes, Mycoplasma, Legionella, Rickettsia, Coxiella,
Chlamydia are termed atypical because they are cannot be classified as
either bacilli or cocci. They are Gram-negative organisms. Bacteria may be
further sub-classified according to oxygen tolerance i.e. aerobes, facultative
anaerobes, or strict anaerobes.
Gram-staining imparts information concerning the cell wall of a bacterium.
Gram-positive bacteria have a peptidoglycan cell wall that envelops the outer
wall of the cell membrane. Gram-negative bacteria also possess a
peptidoglycan cell wall (though it is thinner), but this is enveloped by an
additional outer membrane with surface polysaccharide. This difference
suggests that antibiotics that exert their effects on peptidoglycan cell walls,
such as penicillins, will be less effective against Gram-negative organisms, in
which the cell wall matrix has reduced exposure to antibiotic.
Treatment
General principles
In general, the treatment of perioperative infection involves both the
avoidance of cross infection with other patients and the tailored treatment of
the specific infection affecting the patient. Cross infection may be avoided by
barrier nursing, hand washing and use of alcohol and glycerine hand rubs
between patient contacts, the use of sterile instruments and isolation
methods.
93
Specific patient treatment involves careful clinical assessment, appropriate
investigations, wound care, general treatment (e.g. fluid management,
analgesia, physiotherapy, pressure area care), antibiotic treatment and
reassessment.
Wound care
Ideally the wound should be kept scrupulously clean. Foreign debris (e.g.
drains) should be kept to a minimum, and removed as soon as viable. The
wound should be inspected daily and redressed in a sterile manner with an
appropriate dressing.
The wound should be protected until healing is advanced, and the patient
should be educated to avoid touching or picking at the wound. Topical
antimicrobial agents or antiseptic washes may be employed.
Antibiotics
Without doubt, the discovery and use of antibiotics has saved many lives that
would have otherwise been lost due to perioperative surgical infection.
However, it is important to reiterate that they should only be used as an
adjunct to general hygiene and antisepsis, due to the potential for
development of bacterial resistance. The ideal antibiotic would be cheap, easy
to produce, stable in a low-volume solution, available and effective in oral,
intravenous and topical preparations, be bactericidal against Gram positive
and negative rods and bacilli, spirochaetes and anaerobes, have a wide
therapeutic range with minimal side-effects, be non-allergenic and resilient to
the development of bacterial resistance.
Antibiotic prophylaxis
Prophylactic antibiotics reduce the rate of postoperative infection after
procedures that produce bacteraemia or wound contamination, and in
susceptible patients (e.g. those with valvular heart disease, the
immunocompromised, and patients receiving prosthetic implants). Prophylaxis
alone does not prevent infection, but forms part of the general anti-infection
measures taken in the perioperative period.
A number of broad spectrum antibiotics are used, their choice being
dependent on the type of surgery, the likeliest source of bacterial
contamination, patient factors (e.g. allergy) and local or regional antibiotic
policy. Prophylactic antibiotics are usually administered as a single dose prior
to the operation, the aim being to have a high circulating concentration of
antibiotic at the site of skin incision (they should therefore be administered at
least 5 minutes prior to application of a tourniquet). Prophylaxis may be
carried on into the immediate postoperative phase (up to 24 hours) after
which continued administration is classed as therapeutic. Commonly used
prophylactic regimes are shown in table 5.
Specific antibiotic therapy
There is inevitably a delay between taking a microbiology sample and
obtaining a culture and sensitivity result. Therefore, the initial treatment of
perioperative infections should be based on;
1. clinical assessment of the most likely infecting organism (according to
the type of surgery and the site of infection)
2. the severity of the infection
94
3. Gram stain results
4. local antibiotic policies
5. patient factors (allergy, renal impairment, recent antibiotic
administration).
Common empirical regimens include:
minor surface infections-
narrow spectrum: flucloxacillin (if S aureus) suspected
broad spectrum: cefuroxime
chest infection penicillins
after GI surgery cefuroxime + metronidazole +/- gentamicin
+/- antifungal
after urological surgery co-amoxiclav, gentamicin
severe sepsis vancomycin + gentamicin + metronidazole
MRSA vancomycin
vancomycin resistant consult microbiologist
Pseudomonas suspected ciprofloxacin
Subsequently, therapy should be guided by the appropriate antibiotic
sensitivities obtained after microbiological culture. The main types of
antibiotics currently used are listed in table 6
Table 5 Commonly used prophylactic antibiotics.
Type of surgery Likely infecting organism Prophylactic antibiotic

Cardiac Cefuroxime 750 mg iv or Vancomycin
Vascular S aureus 15mg/kg iv (if cephalosporin sensitive)
Prosthesis placement Coagulase negative
Neurosurgery staphylococci
Thoracic
Orthopaedic
Gastrointestinal Gram ve bacilli, S Cefuroxime 750 mg iv
aureus, Strep faecalis, + Metronidazole 500 mg
Anaerobes iv +/-
Obstetric/gynaecological Gram ve bacilli, S Gentamycin 5 mg/kg iv (3 mg/kg in
aureus, Group B renal disease)
streptococci, Anaerobes
Head and neck (including S aureus, Streptococci,
dental) Anaerobes
Urological Gram-ve bacilli, Strep Gentamycin 120 mg iv
faecalis Amoxycillin/Clavulanic acid 1.2 g iv
Antibiotic resistance
Bacteria may be naturally resistant to antibiotics, or may acquire immunity by
a number of mechanisms. What is clear, however, is that antibiotic resistance
is increasing: species that were formerly sensitive to certain antibiotics have
mutated into resistant forms. Examples include methicillin (i.e. penicillin)
resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
enterococcus (VRE). The development of antibacterial resistance is primarily
due to the indiscriminate use of current antibiotics, such that inadequate
95
doses of broad-spectrum antibiotics are being administered for an inadequate
time period.
Natural bacterial resistance may occur due to:

natural impermeability to antibiotic molecules
a lack of target binding sites
lack of a target metabolic pathway
the production of antibiotic destroying enzymes (eg beta lactamases)
Combinations of beta lactam antibiotics with beta-lactamase inhibiting drugs
(e.g. amoxicillin + clavulanic acid co-amoxiclav) may be effective against
beta lactamase producing bacteria.
Acquired resistance may result from:

alteration in cell wall/membrane permeability
alteration in target binding site (e.g. penicillin resistant S pneumoniae)
alteration in metabolic pathway (e.g. trimethoprim resistance)
gene activation to produce antibiotic destroying enzymes (e.g. aminoglycoside
resistance)
New gene acquisition to produce antibiotic destroying enzymes
96
Table 6. The main groups of antibiotics.
Antibiotic Site of action Effective against Side effect

Beta-lactams (penicillins, Bacterial cell wall Broad spectrum or Hypersensitivity, nausea,
cephalosporins) narrow spectrum vomiting, diarrheah (NVD)
Antimetabolites Bacterial tetrahydrofolate Urinary infections Blood dyscrasias
(Sulphonamides, production ( blocks purine Rashes
trimethoprim) synthesis)
Glycopeptides Bacterial cell wall Severe Gram+ve Blood dyscrasias, renal
(Vancomycin, infections impairment
Teicoplanin)
Quinolones Bacterial DNA gyrase Gram-ve infections, NVD, Cytochrome P450
(Ciprofloxacin) pseudomonas inhibition
Rifampicin Bacterial DNA dependent Gram +ve cocci, Liver enzyme induction,
RNA polymerase mycobacteria Deranged LFTs, Orange
urine
Protein synthesis Gram +ve cocci NVD
inhibitors Bacterial 50S ribosomal Cholestatic jaundice
Macrolides subunit Bacilli Blood dyscrasias, gray baby
(erythromycin) Gram ve bacteria syndrome
Chloramphenical
Bacterial 30S ribosomal Gram ve Adsorbs into gro
Tetracyclines subunit organisms wing bones and teeth
Aminoglycosides Ototoxicity
(gentamycin) Nephrotoxicity
Metronidazole Forms high energy Anaeorobes NVD, Antabuse effect, Taste,
bactericidal free radicals due Neuropathy
to low redox potential
Azole antifungals (e.g. Fungal membrane Yeasts, Candida Mild liver enzyme induction
fluconazole)
Polyene antifungals (e.g. Membrane sterols (bacteria Many fungal Deranged K, magnesium and
amphotericin B) and humans) species LFTs
Nephrotoxicity, Anaemia,
NVD
HIV infection
The human immunodeficiency virus is a retrovirus that infects CD4 (helper)
lymphocytes (amongst others), with the result that cell-mediated immunity to
infection is compromised. Up to 30,000 people are infected with HIV in the
UK, a third of whom remain undiagnosed. 1.3% of the hospital patient
population is infected with HIV. People with HIV infection are surviving longer
due to earlier diagnosis and effective antiretroviral therapy. However,
antiretroviral therapy, usually taken as a combination (triple therapy) of two
nucleoside analogues and a protease inhibitor (e.g. zidovudine AZT), can
have marked side-effects including pancreatic, hepatic and renal dysfunction,
97
peripheral neuropathy, bone marrow suppression and gastrointestinal
disturbances, all of which may debilitate the patient prior to operation.
The normal CD4 count is 0.6-1.5 x 109 cells/l, but falls progressively after
infection. Symptomatic disease typically occurs below 0.2 x 109 cells/l, and is
associated with susceptibility to opportunistic and postoperative infections (the
latter occurring in up to 60% of cases). Opportunistic infections may include
bacteria, viruses (especially herpes simplex (HSV) and varicella zoster (VZV)
viruses, and cytomegalovirus (CMV)), fungi and protozoa, and there is a
greater risk of these being multi-drug resistant. Immunosuppression may be
further worsened by major surgery, anaesthesia, malnutrition, malignancy,
concurrent organ failure and drug abuse.
HIV infected patients may present for any type of surgery. In the absence of
any ethical or practical screening programme, all hospital patients undergoing
surgery are effectively treated as if they might be infected - that is, universal
precautions are employed for every patient. These precautions include:
avoidance of contact between the patients body fluids and healthcare
workers skin or mucous membranes (gowns, gloves, masks/goggles,
avoidance of hollow needles and aerosolisation of fluids),
use of electrocautery, blunt dissection and stapling guns, instead of scalpels
and sutures, use of intermediate receptacles for the handling of sharps.
Guidelines for splash or direct inoculation injuries:

All doctors are obliged to avoid infecting themselves and others. Surgeons
and anaesthetists should seek advice perioperatively from HIV specialists and
microbiologists. In addition, doctors should adopt practices which reduce
exposure of the patient to opportunistic infections. Measures include the use
of skin preparation and scrupulous aseptic technique, microbiological screens
prior to surgery, prophylactic antibiosis and early treatment of suspected
infection and appropriate perioperative isolation procedures including barrier
nursing. Surgery may be deferred until the patient overcomes a concomitant
infection, or until the CD4 count has recovered to an appropriate level (e.g.
above 0.5 x 109 CD4 cells/litre for contaminated surgery).
Postoperative pulmonary infections may be reduced by the appropriate use of
regional anaesthesia, together with chest physiotherapy and early
mobilisation.
The risk of transmission of HIV from a patient to a health care worker is
reported as 1/450,000 to 1/1.3 billion. The risk of transmission of HIV from an
infected surgeon to a patient is 1/130,000. Approximately 6/100 operations
are associated with percutaneous injury to the surgeon. The seroconversion
rate after percutaneous exposure is 0.3%.
Outline of measures to be taken after suspected inoculation from an HIV,
hepatitis B or C infected patient:
(HBIG = hepatitis B immune globulin, PEP = post-exposure prophylaxis).
1. Exposure=>Rinse with water. Disinfect with 70% alcohol
2. Report to responsible department
3. Risk realistic? No=>>No action
4. Yes.
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(a) Sample source for HBV, HCV, HIV source neagative=> stop
=>Source +ve=>with past HBV or full vaccination=> No action
=>Source +ve=>with no past HBV or full vaccination=> hepatitis B
immunoglobulin (HBIG)<48hrs
=>Source ve=> No action
(b) Sample serum (baseline) for
(i) hepatitis B virus:
Hx of past HB or full vaccination=> Stop
No hx of HB or full vaccination=>HIBG<48hrs
(ii) Hepatitis C virus. Source +ve=>follow up after 9-
12 months.
HCV negative=>No infection
HCV positive=> alphainterferon = ribavirin
(iii) Human Immunodeficiency Virus;
Post-exposure prophylaxis (PEP) where
Indicated;
Test source;
1,3,6,12 months follow up=>if HIV test negative
stop PEP (no infection). If HIV test
positive=>treatment by AIDS specialist
Table 7. Potential postoperative infections in HIV infected patients.
Site of sepsis Causative organism

Superficial S aureus, S epidermidis, Coliforms, Bacteroides spp,
wounds/venous access Pseudomonas aeroginosa, HSV, VZV
Deep wounds/prosthesis S aureus, S epidermidis, Coliforms, Bacteroides spp
Respiratory tract S aureus, Pneumocystis carinii, Mycobacterium tuberculosis, S
pneumoniae, Legionella pneumophilia, fungi
GI tract Coliforms, Bacteroides spp, Pseudomonas aeruginosa, Candida
albicans, Cryptosporidiumparvum, Clostridium difficile
Urinary tract Coliforms, Enterococci
CNS CMV, HSV, Toxoplasma gondii, Cryptococcus neoformans
Septicaemia All of the above organisms, if immunosupression is severe
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CHAPTER 12
SURGICAL WOUND AND SURGICAL SITE INFECTION.
Pathophysiology
Wound healing is divided into the following phases: inflammatory phase,
proliferative phase, and maturation phase.
1. The inflammatory phase; begins the coagulation cascade to limit bleeding.
Platelet aggregation and degranulation (platelet reaction) with release
several cytokines (or paracrine growth factors- platelet derived growth factor
(PDGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF),
and fibroblast growth factor (FGF). Serotonin is also released, which, together
with histamine (released by mast cells), induces a reversible opening of the
junctions between the endothelial cells, allowing the passage of neutrophils
and monocytes (which become macrophages) to the site of injury.
This large cellular movement to the injury site is induced by cytokines
secreted by the platelets (chemotaxis) and by further chemotactic cytokines
secreted by the macrophages themselves once at the site of injury. These
include transforming growth factor alpha (TGF-alpha) and transforming growth
factor beta (TGF-beta). Consequently, an inflammatory exudate that contains
red blood cells, neutrophils, macrophages, and plasma proteins, including
coagulation cascade proteins and fibrin strands, fills the wound in a matter of
hours. Macrophages not only scavenge but they also are central to the wound
healing process because of their cytokine secretion.
2. The proliferative phase begins as the cells that migrate to the site of injury,
such as fibroblasts, epithelial cells, and vascular endothelial cells, start to
proliferate and the cellularity of the wound increases. The cytokines involved
in this phase include FGFs, particularly FGF-2 (previously known as basic
FGF), which stimulates angiogenesis and epithelial cell and fibroblast
proliferation. The marginal basal cells at the edge of the wound migrate
across the wound, and, within 48 hours, the entire wound is epithelialized. In
the depth of the wound, the number of inflammatory cells decreases with the
increase in stromal cells, such as fibroblasts and endothelial cells, which in
turn continue to secrete cytokines. Cellular proliferation continues with the
formation of extracellular matrix proteins, including collagen and new
capillaries (angiogenesis). This process is variable in length and may last
several weeks.
3. In the maturation phase, the dominant feature is collagen. The dense
bundle of fibers, characteristic of collagen, is the predominant constituent of
the scar. Wound contraction occurs to some degree in primary closed wounds
but is a pronounced feature in wounds left to close by secondary intention.
The cells responsible for wound contraction are called myofibroblasts, which
resemble fibroblasts but have cytoplasmic actin filaments responsible for
contraction.
The wound continuously undergoes remodeling to try to achieve a state
similar to that prior to injury. The wound has 70-80% of its original tensile
strength at 3-4 months postoperative.
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Frequency
Internationally, the frequency of SSI is difficult to monitor because criteria for
diagnosis might not be standardized. A survey sponsored by the World Health
Organization demonstrated a prevalence of nosocomial infections varying
from 3-21%, with wound infections accounting for 5-34% of the total. The
2002 survey report by the Nosocomial Infection National Surveillance Service
(NINSS), which covers the period between October 1997 and September
2001, indicates that the incidence of hospital acquired infection related to
surgical wounds in the United Kingdom is as high as 10% and costs the
National Health Service in the United Kingdom approximately 1 billion pounds
(1.8 billion dollars) annually.
Collected data on the incidence of wound infections probably underestimate
true incidence because most wound infections occur when the patient is
discharged, and these infections may be treated in the community without
hospital notification.
Mortality/morbidity
SSIs are associated not only with increased morbidity but also with mortality.
Seventy-seven percent of the deaths of surgical patients are related to
surgical wound infection with a relative risk of death of 2.2 attributable to SSIs,
compared to matched surgical patients without infection.
History.
SSI is a difficult term to define accurately because it has a wide spectrum of
possible clinical features. The Centers for Disease Control and Prevention
(CDC) have defined SSI to standardize data collection for the National
Nosocomial Infections Surveillance (NNIS) program. SSIs are classified into
incisional SSIs, which can be superficial or deep, or organ/space SSIs, which
affect the rest of the body other than the body wall layers.
Definitions of SSI
1. Incisional
a). Superficial incisional SSI: Infection involves only skin and subcutaneous
tissue of incision.
b). Deep incisional SSI: Infection involves deep tissues, such as fascial and
muscle layers. This also includes infection involving both superficial and deep
incision sites and organ/space SSI draining through incision.
2. Organ/space SSI: Infection involves any part of the anatomy in organs and
spaces other than the incision, which was opened or manipulated during
operation.
Superficial incisional SSI is more common than deep incisional SSI and
organ/space SSI. Superficial incisional SSI accounts for more than half of all
SSIs for all categories of surgery. The postoperative length of stay is longer
for patients with SSI, and when adjusted for other factors influencing length of
stay.
Physical findings
1). Superficial incisional SSI:
A wound is not considered a superficial incisional SSI if a stitch abscess is
present; if the infection is at an episiotomy, a circumcision site, or a burn
wound; or if the SSI extends into fascia or muscle.
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Occurs within 30 days after the operation
Involves only the skin or subcutaneous tissue
At least one of the following:
i. Purulent drainage is present (culture documentation not required).
ii. Organisms are isolated from fluid/tissue of the superficial incision.
iii.At least 1 sign of inflammation (eg, pain or tenderness, induration,
erythema, local warmth of the wound) is present.
iv. The wound is deliberately opened by the surgeon.
v. The surgeon or attending physician declares the wound infected.
2). Deep incisional SSI
Occurs within 30 days of the operation or within 1 year if an implant is present
Involves deep soft tissues (eg, fascia and/or muscle) of the incision
At least 1 of the following:
i.Purulent drainage is present from the deep incision but without organ/space
involvement.
ii.Fascial dehiscence or fascia is deliberately separated by the surgeon
because of signs of inflammation.
iii.A deep abscess is identified by direct examination or during reoperation, by
histopathology, or by radiologic examination.
iv.The surgeon or attending physician declares that a deep incisional infection
is present.
3). Organ/space SSI
Occurs within 30 days of the operation or within 1 year if an implant is present
Involves anatomical structures not opened or manipulated during the
operation
At least 1 of the following:
i.Purulent drainage is present from a drain placed by a stab wound into the
organ/space.
ii. Organisms are isolated from the organ/space by aseptic culturing
technique.
iii. An abscess in the organ/space is identified by direct examination, during
reoperation, or by histopathologic or radiologic examination.
iv. A diagnosis of organ/space SSI is made by the surgeon or attending
physician.
Causes
All surgical wounds are contaminated by microbes, but in most cases,
infection does not develop because innate host defenses are quite efficient in
the elimination of contaminants. A complex interplay between host, microbial,
and surgical factors ultimately determines the prevention or establishment of a
wound infection.
Factors that affect surgical wound healing are classified as;
i). Microbiology: Microbial factors that influence the establishment of a wound
infection are the bacterial inoculum, virulence, and the effect of the
microenvironment. When these microbial factors are conducive, impaired host
defenses set the stage for enacting the chain of events that produce wound
infection. Most SSIs are contaminated by the patient's own endogenous
flora, which are present on the skin, mucous membranes, or hollow viscera.
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The traditional microbial concentration quoted as being highly associated with
SSIs is that of bacterial counts higher than 10,000 organisms per gram of
tissue .
The usual pathogens on skin and mucosal surfaces are gram-positive cocci
(notably staphylococci); however, gram-negative aerobes and anaerobic
bacteria contaminate skin in the groin/perineal areas. The contaminating
pathogens in gastrointestinal surgery are the multitude of intrinsic bowel flora,
which include gram-negative bacilli (eg, Escherichia coli) and gram-positive
microbes, including enterococci and anaerobic organisms. Gram-positive
organisms, particularly staphylococci and streptococci, account for most
exogenous flora involved in SSIs. Sources of such pathogens include
surgical/hospital personnel and intraoperative circumstances, including
surgical instruments, articles brought into the operative field, and the
operating room air.
The most common group of bacteria responsible for SSIs are Staphylococcus
aureus. The emergence of resistant strains has considerably increased the
burden of morbidity and mortality associated with wound infections. Methicillin
resistant Staphylococcus aureus (MRSA) is proving to be the scourge of
modern day surgery. Like other strains of S aureus, MRSA can colonize the
skin and body of an individual without causing sickness, and, in this way, it
can be passed on to other individuals unknowingly. Problems arise in the
treatment of overt infections with MRSA because antibiotic choice is very
limited. MRSA infections appear to be increasing in frequency and are
displaying resistance to a wider range of antibiotics. Of particular concern are
the vancomycin intermediate Staphylococcus aureus (VISA) strains of MRSA.
These strains are beginning to develop resistance to vancomycin, which is
currently the most effective antibiotic against MRSA. This new resistance has
arisen because another species of bacteria, called enterococci, relatively
commonly express vancomycin resistance.
ii). Risk factors (other than microbiology)
Decreased host resistance can be due to systemic factors affecting the
patient's healing response, local wound characteristics, or operative
characteristics.
a). Systemic factors include age, malnutrition, hypovolemia, poor tissue
perfusion, obesity, diabetes, steroids, and other immunosuppressants.
b). Wound characteristics include nonviable tissue in wound; hematoma;
foreign material, including drains and sutures; dead space; poor skin
preparation, including shaving; and preexistent sepsis (local or distant).
c). Operative characteristics include poor surgical technique; lengthy
operation (>2 h); intraoperative contamination, including infected theater staff
and instruments and inadequate theater ventilation; prolonged preoperative
stay in the hospital; and hypothermia.
iii).The type of procedure is a risk factor. Certain procedures are associated
with a higher risk of wound contamination than others.
Surgical wounds have been classified as clean, clean-contaminated,

contaminated, and dirty-infected.
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Table 1. Pathogens Commonly Associated with Wound Infections and Frequency of

Occurrence
Pathogen Frequency (%)

Staphylococcus aureus 20
Coagulase-negative staphylococci 14
Enterococci 12
Escherichia coli 8
Pseudomonas aeruginosa 8
Enterobacter species 7
Proteus mirabilis 3
Klebsiella pneumoniae 3
Other streptococci 3
Candida albicans 3
Group D streptococci 3
Other gram positive aerobes 2
Bacteroides fragilis 2
Table 2: Surgical Wound Classification and Subsequent Risk of Infection
Classification Description Infective

risk (%)
Clean (Class I) Uninfected operative wound. No acute inflammation. Closed <2
primarily. Respiratory, gastrointestinal, biliary, and urinary
tracts not entered. No break in aseptic technique. Closed
drainage used if necessary.
Clean Elective entry into respiratory, biliary, gastrointestinal, <10
contaminated urinary tracts and with minimal spillage. No evidence of
(Class II) infection or major break in aseptic technique.
Appendicectomy
Contaminated Nonpurulent inflammation present. Gross spillage from About 20
(Class III) gastrointestinal tract. Penetrating traumatic wounds <4
hours. Major break in aseptic technique
Dirty-infected Purulent inflammation present. Preoperative perforation of About 40
(Class IV) viscera. Penetrating traumatic wounds >4 hours
Investigations
Laboratory studies.
Staining methods: The simplest, and usually the quickest, method involves
obtaining a Gram stain for infective organisms. Staining for fungal elements
can be obtained at the same time.
Culture techniques: Most laboratories routinely will culture for both aerobic
and anaerobic organisms. Fungal cultures can be requested. Isolation of
single colonies allows further growth and identification of the specific
organism. Sensitivity testing then follows mainly for aerobic organisms.
Newer techniques
Tests for antigens from the organism through enzyme-linked immunoassay
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(ELISA) or radioimmunoassay
Detection of antibody response to the organism in the host sera
Detection of RNA or DNA sequences or protein from the infective organism by
Northern, Southern, or Western blotting, respectively
Polymerase chain reaction (PCR) is a sensitive assay to detect small amounts
of microbe DNA.
Imaging studies
Ultrasound can be applied to the infected wound area to assess whether any
collection needs drainage.
Treatment.
Medical care
The use of antibiotics was a milestone in the effort to prevent wound infection.
The concept of prophylactic antibiotics was established in the 1960s when
experimental data established that antibiotics had to be in the circulatory
system at a high enough dose at the time of incision to be effective.
General agreement exists that prophylactic antibiotics are indicated for clean-
contaminated and contaminated wounds (see Table 2). Antibiotics for dirty
wounds are part of the treatment because infection is established already.
Clean procedures might be an issue of debate. No doubt exists regarding the
use of prophylactic antibiotics in clean procedures in which prosthetic devices
are inserted because infection in these cases would be disastrous for the
patient. However, other clean procedures (eg, breast surgery) may be a
matter of contention.
Criteria for the use of systemic preventive antibiotics in surgical procedures
are as follows:
i). A high risk of infection is associated with the procedure (eg, colon
resection).
ii). Consequences of infection are unusually severe (eg, total joint
replacement).
iii). The patient has a high National nosocomial infection surveillance (NNIS)
risk index.
The antibiotic should be administered preoperatively but as close to the time
of the incision as is clinically practical. Antibiotics should be administered
before induction of anesthesia in most situations.
The antibiotic selected should have activity against the pathogens likely to be
encountered in the procedure.
Postoperative administration of preventive systemic antibiotics beyond 24
hours has not been demonstrated to reduce the risk of SSIs.
Qualities of prophylactic antibiotics include efficacy against predicted bacterial
microorganisms most likely to cause infection, good tissue penetration to
reach wound involved, cost effectiveness, and minimal disturbance to intrinsic
body flora (eg, gut).
The timing of administration is critically important because the concentration
of the antibiotic should be at therapeutic levels at the time of incision, during
the surgical procedure, and, ideally, for a few hours postoperatively.
Administration of the antibiotic is by IV; 30 minutes prior to incision is the
recommended time. Antibiotics should not be administered more than 2 hours
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prior to surgery. Colorectal surgical prophylaxis additionally requires bowel
clearance with enemas and oral nonabsorbable antimicrobial agents 1 hour
before surgery. High-risk cesarean surgical cases require antibiotic
administration as soon as the clamping of the umbilical cord is completed.
Table 3. Recommendations for Prophylactic Antibiotics as Indicated by

Probable Infective Microorganism Involved
Operation Expected pathogen Recommended antibiotic

Orthopaedic surgery (including Staph aureus, coagulase negative Cephazolin 1-2 g
prosthesis insertion), cardiac surgery, staphylococci
neurosurgery, breast surgery, non
cardiac thoracic procedures
Appendicectomy, biliary procedures Gram negative bacilli and anaerobes Cephazolin 1-2 g
Colorectal surgery Gram negative bacilli and anaerobes Cefotetan 1-2 g or cefoxitin 1-2
g, oral neomycin 1 g, oral
erythromycin 1 g (start 19 hours
preoperatively, 3 doses)
Gastrodudodenal surgery Gram negative bacilli and Cefazolin 1-2 g
streptococci
Vascular surgery S aureus, staphylococcus Cefazolin 1-2 g
epidermidis, gram negative bacilli
Head and neck surgery S aureus, streptococci, anaerobes Cefazolin 1-2 g
and streptococci present in an
oropharyryngeal approach
Obstetrics and gynaecological Gram negative bacilli, enterococci, Cefazolin 1-2 g
procedures anaerobes, group B streptococci
Urology procedures Gram negative bacilli Cefazolin 1-2 g
The current risk index used to predict the risk of developing a wound infection
is the NNIS system of the CDC. The risk index category is established by the
added total of the risk factors present at the time of surgery. For each risk
factor present, a point is allocated; risk index values range from 0-3. This risk
index is a better predictor for SSIs than the surgical wound classification (see
Table 2).
The NNIS risk index integrates the 3 main determinants of infection, namely,
bacteria, local environment, and systemic host defenses (patient health
status). The risk index does not include other risk variables, like smoking,
tissue oxygen tension, glucose control, shock, and maintenance of
normothermia. All these factors are relevant for clinicians but difficult to
monitor and fit into a manageable risk assessment.
The elements constituting this index are as follows:
a). Preoperative patient physical status assessed by the anesthesiologist and
classified by the American Society of Anesthesiologists (see Table 4) as
greater than 3
b). Operation status as either contaminated or dirty-infected (see Table 2)
c) Operation lasting longer than T hours, where T is the 75th percentile of the
specific operation performed
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Table 4. American Society of Anesthesiologists (ASA) Classification of Physical Status
ASA Score Characteristics

1 Normal healthy patient
2 Patient with mild systemic disease
3 Patient with a severe systemic disease that limits activity but is not incapacitating
4 Patient with an incapacitating systemic disease that is a constant threat to life
5 Moribund patient not expected to survive 24 hours with or without operation
Table 5. Predictive Percentage of SSI Occurrence by Wound Type and Risk Index
At risk index Predictive Percentage of SSI

0 1.5
1 2.9
2 6.8
3 13.0
Patient preparation
Identify and treat all infections remote from the surgical site.
Delay operation in elective cases until infection is treated.
Do not remove hair unless it infringes on the surgical field. If hair removal is
required, it should be removed immediately before operation and preferably
with electric clippers.
Patients should cease tobacco consumption in any form for at least 1 month
preoperatively.
Optimize blood glucose level and avoid hyperglycemia.
Patients are to shower/bathe with antiseptic on at least the night before
surgery.
Necessary blood products may be administered.
Minimize preoperative hospital stay.
Gradual reduction/discontinuation steroid use before elective surgery
Enhanced nutritional intake solely to prevent SSI
Preoperative topical antibiotic use in nares to prevent SSI
Measures to enhance wound space oxygenation
Surgical team members:
Keep fingernails short; do not wear artificial nails.
Scrub hands and forearms as high as the elbows for at least 2-5 minutes with
appropriate antiseptic.
After scrub, keep hands up with elbows flexed and away from the body; use a
sterile towel to dry the hands and put on a sterile gown and gloves. Masks
should be worn in the operating suite if sterile instruments are exposed and
throughout the surgical procedure. Masks should cover the mouth and nose.
The hair on the head and face is to be covered with a hood or cap. Liquid-
resistant sterile surgical gowns and sterile gloves are to be worn by scrubbed
surgical team members.
Visibly soiled gowns are to be changed.
Shoe covers are not necessary.
Routine exclusion of personnel colonized by organisms such as
Staphylococcus aureus or group A streptococci is not necessary unless they
107
are specifically linked to dissemination of such organisms.
Personnel with skin lesions that are draining are to be excluded from duty until
treated and the infection has resolved.
Educate and encourage surgical personnel regarding reporting illness of
transmissible nature to supervisory and occupational health personnel.
Policies should be established concerning patient care responsibilities for
personnel with potentially transmissible infective illnesses. This should include
aspects of work restrictions, personnel responsibility in utilizing health
services, and declaring illness. Policies also should direct the responsible
person to remove personnel from duty, and policy should be established for
clearance to resume work.
Preoperative and postoperative wound care:
Asepsis is necessary in the insertion of indwelling catheters, such as
intravascular, spinal, or epidural catheters, and subsequent infusion of drugs
Handle tissues gently with good hemostasis, minimize foreign bodies, and
minimize devitalized tissue and dead space.
For Class III and IV wounds use delayed closure or leave the wound incision
open to heal by secondary intention.
If draining of a wound is necessary, the drain exit should be via separate
incision distant from the wound. Remove the drain as soon as possible.
Primary closed incisions should be protected with a sterile dressing for 24-48
hours.
Hands are to be washed before and after wound dressing changes/or contact.
Use sterile technique for wound dressing change.
Educate the patient and relatives regarding wound care symptoms of SSIs
and the need to report such problems.
Theater environment and care of instrumentation
Maintain positive pressure ventilation of the operating suite relative to
corridors and surrounding areas.
Maintain a minimum of 15 air changes per hour, with a minimum of 3 being
fresh air.
Appropriate filters (as recommended by the American Institute of Architects)
should be used for filtration of all air whether recirculated or fresh.
Air should enter through the ceiling and exit near the floor.
Keep operating room doors closed except for necessary entry.
The use of ultraviolet lamps in the theater is not necessary as a deterrent of
SSI.
Prior to subsequent procedures, visibly soiled surfaces should be cleaned
with disinfectants.
Following a contaminated or dirty procedure, special cleaning or closure of the
operating suite is not necessary.
Use of tacky mats prior to entry in the operating suite is not necessary. Sterile
surgical instruments and solutes should be assembled just prior to use.
All surgical instruments should be sterilized according to guidelines. Flush
sterilization should only be used for instruments that are required for
immediate patient use.
Limit the number of personnel entering the operating suite.
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Orthopedic implant surgery should be performed in an ultra clean air
environment.
Wet vacuum the floor of the operating theater at the end of day/night using
disinfectants.
Special situations
Elective colon surgery: Bowel surgery results in the breakdown of the
protective intestinal mucous membrane, with release of the facultative and
anaerobic bacteria that heavily colonize the distal small bowel and colon.
Eradication of aerobes and anaerobes is necessary to reduce infective
complications following intestinal procedures. Mechanical cleansing and
antibiotics could achieve this. Mechanical cleansing for colonic surgery can
take the form of dietary restrictions; whole gut lavage with one of several
recommended preparations. Enteral antibiotic regimes to eradicate intrinsic
bowel flora vary, with oral neomycin and erythromycin. Other combinations
with neomycin include the use of metronidazole and tetracycline. Prophylactic
parenteral antibiotics also are used with the above as recommended in Table
3.
Intravascular device-related infections:
Intravascular devices are of vital use in daily hospital practice. Their use is for
the parenteral administration of fluids, blood products, nutrition fluids,
medication, and access to hemodialysis; equally important is their use in the
monitoring of critically ill patients. Unfortunately, because their use constitutes
an invasive procedure, they are associated with infectious complications that
could be of a local or systemic nature. Recommendations for prevention and
treatment are available to limit their associated morbidity and mortality (which
could be as high as 20% in patients with catheter-related bloodstream
infections).
Surgical care
Although the goal of every surgeon is to prevent wound infections, they will
arise. Treatment is individualized to the patient, the wound, and the nature of
the infection. The operating surgeon should be made aware of the possibility
of infection in the wound and determine the treatment for the wound.
Ideally, surgical care should start with meticulous detail to strategies that
prevent the development of SSIs in the first place. Preoperatively, attention
should be paid to factors like optimization of patient status, proper asepsis,
and surgical site preparation. Intraoperatively, adherence to good basic
surgical principles of minimal and fine tissue dissection, proper selection of
suture materials, and proper wound closure is important.
If a SSI sets in, the treatment often involves opening the wound, evacuating
pus, and cleansing the wound. The deeper tissues are inspected for integrity
and for a deep space infection or source. Dressing changes allow the tissues
to granulate, and the wound heals by secondary intention over several weeks.
Early/delayed closure of infected wounds is often associated with relapse of
infection and wound dehiscence.
Newer concepts in the prevention of SSIs
Evidence shows that the close regulation of blood sugar may be a major
determinant of wound morbidity. Although investigators have vigorously
109
pursued for decades the identification of a specific innate or acquired immune
deficiency among patients with diabetes, it may be the blood sugar that is the
determinant of infection for these patients.
A second issue of considerable interest is body temperature. There is now a
prospective randomized study that demonstrates that failure to maintain
intraoperative core body temperature within 1-1.5C of normal increases the
SSI rate by a factor of 2.
The third issue is oxygenation. The fresh, hemostatic surgical incision is a
hypoxic, ischemic environment. Maintaining or increasing oxygen delivery to
the wound by increasing the inspired oxygen concentration administered to
the patient perioperatively has also been shown to reduce the incidence of
SSIs. It is presumed that increased oxygen availability is a positive host
factor, perhaps via enhanced production of oxidant products that facilitate
phagocytic eradication of microbes.
Future strategies
The establishment of dedicated infection surveillance units in hospitals that
aim to accomplish the following:
Identify epidemics by common or uncommon organisms.
Establish the correct use of prophylaxis (ie, timing, dose, duration, choice).
Document costs, risk factors, and readmission rates.
Monitor postdischarge infections and secondary consequences.
Ensure patient safety.
Preventing the emergence of resistance: Although resistance is not a new
phenomenon, the incidence has increased dramatically over the past 2
decades. The development of new drugs has slowed considerably and may
be unable to keep pace with the continuing growth of pathogen resistance.
Therefore, effective strategies are needed to prevent the continuing
emergence of antimicrobial resistance. These strategies include avoiding
unnecessary antibiotic administration and increasing the effectiveness of
prescribed antibiotics, as well as implementing improvements in infection
control and optimizing medical practice.
Although an SSI rate of zero may not be achievable, continued progress in
understanding the biology of infection at the surgical site and consistent
applications of proven methods of prevention will further reduce the
frequency, cost, and morbidity associated with SSIs.
Medication
The choice of antibiotic depends on 2 factors, the patient and the known or
probable infecting microorganism.
Patient factors include allergies, hepatic and renal function, severity of
disease process, interaction with other medication(s), and age. In women,
pregnancy and breastfeeding must be considered.
Antibiotics
Therapy must be comprehensive and cover all likely pathogens in the context
of this clinical setting.
Cefazolin (Ancef, Kefzol, Zolicef)
First-generation semisynthetic cephalosporin that arrests bacterial cell wall
synthesis, inhibiting bacterial growth. Primarily active against skin flora,
110
including Staphylococcus aureus. Typically used alone for skin and skin-
structure coverage. IV and IM dosing regimens are similar. 250 mg to 2 g
IV/IM q6-12h depending on severity of infection; not to exceed 12 g/d.
Paediatric dose; 25-100 mg/kg/d IV/IM divided q6-8h depending on severity of
infection; not to exceed 6 g/d. Contrainidications; Documented
hypersensitivity, Probenecid prolongs effect; coadministration with
aminoglycosides may increase renal toxicity; may yield false-positive urine-dip
test for glucose. Pregnancy; Usually safe but benefits must outweigh the
risks. Precautions; Adjust dose in renal impairment; superinfections and
promotion of nonsusceptible organisms may occur with prolonged use or
repeated therapy.
Erythromycin
Inhibits bacterial growth possibly by blocking dissociation of peptidyl tRNA
from ribosomes, causing RNA-dependent protein synthesis to arrest. For
treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage.
When bid dosing is desired, half-total daily dose may be taken q12h. For more
severe infections, double the dose. 250 mg erythromycin (stearate, base) or
400 mg ethylsuccinate q6h PO 1 h ac or 500 mg q12h; alternatively, 333 mg
q8h; increase to 4 g/d depending on severity of infection. Paediatric dose; 30-
50 mg/kg/d (15-25 mg/lb/d) PO divided q6-8h; double dose for severe
infection. Contraindications; Documented hypersensitivity; hepatic
impairment. Interactions; Coadministration may increase toxicity of
theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate
anticoagulant effects of warfarin; coadministration with lovastatin and
simvastatin increases risk of rhabdomyolysis. Pregnancy; Usually safe but
benefits must outweigh the risks. Precautions; Caution in liver disease;
estolate formulation may cause cholestatic jaundice; GI adverse effects are
common (administer ac); discontinue use if nausea, vomiting, malaise,
abdominal colic, or fever occur
Cefoxitin (Mefoxin)
Second-generation cephalosporin indicated for gram-positive cocci and gram-
negative rod infections. Infections caused by cephalosporin- or penicillin-
resistant gram-negative bacteria may respond to cefoxitin. 1-2 g IV q6-8h.
Paediatric dose; Infants and children: 80-160 mg/kg/d IV divided q4-6h; higher
doses for severe or serious infections; not to exceed 12 g/d.
Contraindications; Documented hypersensitivity. Interactions; Probenecid may
increase effects of cefoxitin; coadministration with aminoglycosides or
furosemide may increase nephrotoxicity (closely monitor renal function).
Pregnancy; Usually safe but benefits must outweigh the risks. Precautions;
Bacterial or fungal overgrowth of nonsusceptible organisms may occur with
prolonged use or repeated treatment; caution in patients with previously
diagnosed colitis
Cefotetan (Cefotan)
Second-generation cephalosporin indicated for infections caused by
susceptible gram-positive cocci and gram-negative rods.
Dose and route of administration depend on condition of patient, severity of
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infection, and susceptibility of causative organism. 1-2 g IV/IM q12h for 5-10
d. paediatric dose; 20-40 mg/kg/dose IV/IM q12h for 5-10 d.
Contraindications; Documented hypersensitivity. Interactions; Consumption of
alcohol within 72 h of cefotetan may produce disulfiramlike reactions;
cefotetan may increase hypoprothrombinemic effects of anticoagulants;
coadministration with potent diuretics (eg, loop diuretics) or aminoglycosides
may increase nephrotoxicity. Pregnancy; Usually safe but benefits must
outweigh the risks. Precautions; Reduce dose by one half if Creatinine
Clearance (CrCl) <10-30 mL/min and by one fourth if CrCl <10 mL/min;
bacterial or fungal overgrowth of nonsusceptible organisms may occur with
prolonged or repeated therapy
Followup
Inpatient
Resultant increased hospital stay due to SSI has been estimated at 7-10
days, increasing hospitalization costs by 20%.
Occasionally, further intervention in the form of wound debridement and
subsequent packing and frequent dressing is necessary to allow healing by
secondary intention.
Outpatient.
Most patients with wound infections are managed in the community.
Management usually takes the form of dressing changes to optimize healing,
which usually is by secondary intention.
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CHAPTER 13
GAS EMBOLISM. DIAGNOSIS AND MANAGEMENT.
Gas embolism, the entry of gas into vascular structures, is a largely iatrogenic
clinical problem that can result in serious morbidity and even death. Since gas
embolism can result from procedures performed in almost all clinical
specialties, it is important for all clinicians to be aware of this problem. In most
cases, gas embolism is air embolism, although the medical use of other
gases, such as carbon dioxide, nitrous oxide, and nitrogen, can also result in
the condition. There are two broad categories of gas embolism, venous and
arterial, which are distinguished by the mechanism of gas entry and the site
where the emboli ultimately lodge.
Venous Gas Embolism
Venous gas embolism occurs when gas enters the systemic venous system.
The gas is transported to the lungs through the pulmonary arteries, causing
interference with gas exchange, cardiac arrhythmias, pulmonary hypertension,
right ventricular strain, and eventually cardiac failure. Physical preconditions
for the entry of gas into the venous system are the incising of noncollapsed
veins and the presence of subatmospheric pressure in these vessels.
Noncollapsing veins include the epiploic veins, the emissary veins, and the
dural venous sinuses. Air may enter these veins during neurosurgical
operations, especially those performed with the patient in the sitting position.
The veins of the throat, and in some cases the veins in the coagulated
operative field, may also be entryways for air. Air may also enter veins through
central venous and hemodialysis catheters and may enter the veins of the
myometrium during pregnancy and after delivery.
Pathophysiology
The most frequent form of venous gas embolism is the insidious venous
aeroembolism, in which a series of gas bubbles resembling a string of pearls
enters the venous system. Rapid entry or large volumes of gas put a strain on
the right ventricle because of the migration of the emboli to the pulmonary
circulation. The pulmonary arterial pressure increases, and the increased
resistance to right ventricular outflow causes diminished pulmonary venous
return. Because of the diminished pulmonary venous return, there is
decreased left ventricular preload, resulting in diminished cardiac output and,
ultimately, systemic cardiovascular collapse. Tachyarrhythmias often develop,
but bradycardias are possible as well. When large quantities of gas (over 50
ml) are injected abruptly, acute cor pulmonale, asystole, or both are likely to
occur. The alteration in the resistance of the lung vessels and the mismatch
between ventilation and perfusion cause intrapulmonary right-to-left shunting
and increased alveolar dead space, leading to arterial hypoxia and
hypercapnia.
Diagnosis
To diagnose venous gas embolism, the physician should assess the clinical
findings. The so-called mill-wheel murmur, a splashing auscultatory sound due
to the presence of gas in the cardiac chambers and great vessels, is often
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present and can be auscultated by a precordial or esophageal stethoscope. A
decrease in the end-tidal carbon dioxide levels, as determined by capnometry,
suggests a change in the relation between ventilation and perfusion due to the
obstruction of the pulmonary arteries. Doppler ultrasonography is a sensitive
and practical means of detecting intracardiac air, and it is often used during
neurosurgical procedures with the patient in the sitting position, and other
procedures that entail a high risk of gas embolism. An even more sensitive
and definitive method for detecting intracardiac gas is transesophageal
echocardiography, although it requires training in performance and
interpretation.
Treatment
When venous gas embolism is suspected, further entry of gas must be
prevented. In certain cases, therapy with catecholamines is required, and, if
necessary, aggressive cardiopulmonary resuscitation is performed. Adequate
oxygenation is often possible only with an increase in the oxygen
concentration of the inspired gas (up to 100 percent oxygen). Supplemental
oxygen also reduces the size of the gas embolus by increasing the gradient
for the egress of nitrogen from the bubble. Rapid resuscitation with volume
expansion is recommended to elevate venous pressure, thus preventing the
continued entry of gas into the venous circulation.
Some authors recommend attempting to evacuate air from the right ventricle
with the use of a central venous catheter (a multiorifice catheter may be more
effective than one with a single lumen) or a pulmonary arterial catheter. It
may be possible to aspirate about 50 percent of the entrained air from an
appropriately placed right atrial catheter, but depending on the placement of
the catheter and the position of the patient, a smaller effect is more likely.
Hyperbaric oxygen therapy is not a first-line treatment but may be a useful
adjunct in severe cases. It should certainly be considered if there is evidence
of neurologic changes. In this case, it should be assumed that a paradoxical
embolism is present.
Paradoxical Embolism
A paradoxical embolism occurs when air or gas that has entered the venous
circulation manages to enter the systemic arterial circulation and causes
symptoms of end-artery obstruction. There are a number of mechanisms by
which this can occur. One is the passage of gas across a patent foramen
ovale into the systemic circulation. A patent foramen ovale, which is
detectable in about 30 percent of the general population, makes possible
right-to-left shunting of gas bubbles. If there is a patent foramen ovale and if
the pressure in the right atrium exceeds the pressure in the left atrium, right-
to-left flow through the foramen ovale may occur. Elevated pulmonary arterial
pressure due to venous gas embolism may result in elevated right atrial
pressure, making it possible for a bubble to be transported through a patent
foramen. Furthermore, the decrease in left atrial pressure caused by
controlled ventilation and the use of positive end-expiratory pressure may
create a pressure gradient across the patent foramen ovale, favoring the
passage of gas into the systemic circulation. In other situations, venous gas
may enter the arterial circulation by overwhelming the mechanisms that
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normally prevent arterial gas embolism. There have been reports of fatal
cerebral arterial gas embolism caused by a large venous gas embolus,
although no intracardiac defects or shunt mechanisms could be demonstrated.
Various anesthetic agents diminish the ability of the pulmonary circulation to
filter out gas emboli.
The treatment of paradoxical embolism is identical to that of primary arterial
gas embolism. Every venous gas embolism has the potential to evolve into an
arterial gas embolism.
Arterial Gas Embolism
Arterial gas embolism is caused by the entry of gas into the pulmonary veins
or directly into the arteries of the systemic circulation. Gas may enter the
arteries as a result of overexpansion of the lung by decompression
barotrauma or as a result of paradoxical embolism. Any cardiac surgical
operation that uses extracorporeal bypass may also cause arterial gas
embolism. Even if only small amounts of gas enter the arterial system, the
flow of gas bubbles into functional end arteries occludes these vessels.
Although obstruction is possible in any artery, obstruction of either the
coronary arteries or the nutritive arteries of the brain (cerebral arterial gas
embolism) is especially serious and may be fatal because of the vulnerability
of the heart and brain to short periods of hypoxia.
Pathophysiology
The entry of gas into the aorta causes the distribution of gas bubbles into
nearly all organs. Small emboli in the vessels of the skeletal muscles or
viscera are well tolerated, but embolization to the cerebral or coronary
circulation may result in severe morbidity or death.
Embolization into the coronary arteries induces electrocardiographic changes
typical of ischemia and infarction; dysrhythmias, myocardial suppression,
cardiac failure, and cardiac arrest are all possible, depending on the amount
of gas embolized. Circulatory responses may also be seen with embolization
to the cerebral vessels.
Cerebral arterial gas embolization typically involves the migration of gas to
small arteries (average diameter, 30 to 60 m). The emboli cause pathologic
changes by two mechanisms: a reduction in perfusion distal to the obstruction
and an inflammatory response to the bubble.
Symptoms
The symptoms of cerebral arterial gas embolism develop suddenly. The
clinical presentation, however, is determined by the absolute quantity of gas
and the areas of the brain that are affected. Thus, there may be minor motor
weakness and headache or moderate confusion; conversely, complete
disorientation, hemiparesis, convulsions, loss of consciousness, and coma
may occur. Asymmetry of the pupils, hemianopia, and impairment of the
respiratory and circulatory centers (manifested as bradypnea, CheyneStokes
breathing, cardiac arrhythmias, and circulatory failure) are other well-known
complications. In patients who have undergone surgical procedures that carry
a risk of gas embolism, a delayed recovery from general anesthesia or a
transitional stage of impaired consciousness may be a clue to the occurrence
of cerebral arterial gas embolism. The diagnosis is not easy to establish in
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such patients, because complications of anesthesia, such as the central
anticholinergic syndrome or the presence of residual anesthetic or muscle
relaxant, can mimic mild cerebral arterial gas embolism.
Diagnosis
The most important diagnostic criterion is the patient's history, because the
clinical suspicion of embolism is based on the initial neurologic symptoms and
the direct temporal relation between these symptoms and the performance of
an invasive procedure. The procedures that carry the greatest risk of venous
or arterial gas embolism are craniotomy performed with the patient in the
sitting position, cesarean section, hip replacement, and cardiac surgery with
cardiopulmonary bypass. All these procedures have in common an incised
vascular bed and a hydrostatic gradient favoring the intravascular entry of gas.
Cerebral arterial gas embolism can sometimes be distinguished from a
cerebral infarct or intracerebral bleeding on a computed tomographic (CT)
scan. However, pathologic changes are sometimes very subtle and not well
visualized on CT, and the diagnosis of cerebral arterial gas embolism must be
considered early. Magnetic resonance imaging of the cerebrum can
sometimes show an increased volume of water concentrated in the injured
tissue. But this method is also not reliable and may fail to detect an embolism
if the symptoms are mild.
Gas bubbles in the vessels of the retina can occasionally be identified, but
their absence does not rule out gas embolism. Another finding that is
nonspecific but that has been described in a number of cases is
hemoconcentration with an increase in the hematocrit, possibly as a direct
consequence of the extravascular shift of fluid into the injured tissues.
Treatment
The primary goal of treatment is the protection and maintenance of vital
functions. If necessary, cardiopulmonary resuscitation should be performed,
since not only venous but also primary arterial gas embolism may lead to
serious impairment of the cardiovascular system. Endotracheal intubation
should be performed in a somnolent or comatose patient in order to maintain
adequate oxygenation and ventilation.
Oxygen should also be administered, at as high a concentration as possible.
Administration of oxygen is important not only to treat hypoxia and hypoxemia
but also to eliminate the gas in the bubbles by establishing a diffusion gradient
that favors the egress of gas from the bubbles.
It is currently recommended that patients with arterial gas embolism be placed
in the flat supine position. The buoyancy of gas bubbles is not sufficient to
counteract blood flow propelling such bubbles toward the head, even when
the patient is placed in a head-down position. In addition, the head-down
position may aggravate the cerebral edema that develops in these patients.
Treatment of Generalized Seizures

Cerebral gas embolism often causes generalized seizures, which may not
respond to benzodiazepines. In these cases, it is recommended that the
seizures be suppressed with barbiturates. Although there is no proof that
barbiturates provide cerebral protection after cerebral ischemia, the use of
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barbiturates for ischemic brain lesions has certain advantages. They reduce
cerebral oxygen consumption, intracranial pressure, the production of free
radicals, and the release of endogenous catecholamines. High doses of
barbiturates depress respiration; ventilatory support must therefore be
available when a patient is given barbiturates.
Hyperbaric-Oxygen Therapy
With hyperbaric-oxygen therapy, the patient breathes 100 percent oxygen at a
pressure above that of the atmosphere at sea level. This therapy decreases
the size of the gas bubble both by raising the ambient pressure and by
causing systemic hyperoxia. An arterial partial pressure of oxygen greater
than 2000 mm Hg is frequently achieved. The hyperoxia produces enormous
diffusion gradients for oxygen into the bubble and for nitrogen out of the
bubble. The hyperoxia also allows much larger quantities of oxygen to be
dissolved in the plasma and increases the extent of oxygen diffusion in
tissues. The improvements in the oxygen-carrying capacity of plasma and in
the delivery of oxygen to tissues offset the embolic insult to the
microvasculature.
Other benefits of hyperbaric oxygen have been proposed. It may help prevent
cerebral edema by reducing the permeability of blood vessels while supporting
the integrity of the bloodbrain barrier. These benefits suggest that all patients
with clinical symptoms of arterial gas embolism should receive recompression
treatment with hyperbaric oxygen. Although immediate recompression
produces the best response, delayed treatment in a hyperbaric chamber may
still be indicated to ameliorate the patient's condition. Hyperbaric oxygen is
the first-line treatment of choice for arterial gas embolism. Thus, as soon as
cardiopulmonary stabilization has been achieved, the patient should be
transferred to a hyperbaric chamber.
Infusion Therapy
There is some evidence that gas embolism may cause hemoconcentration,
which increases blood viscosity and impairs the already compromised
microcirculation. Therefore, normovolemia should be achieved to optimize the
microcirculation. Hypovolemia is always tolerated less well than relative
anemia. It is therefore acceptable to decrease the hematocrit, within certain
limits. Colloid solutions are preferable to crystalloid solutions for hemodilution,
because the latter may promote cerebral edema. Hypertonic solutions (e.g.,
7.5 percent sodium chloride solution) may become the first choice for volume
replacement, but their use is still controversial and therefore cannot yet be
recommended.
The goal of infusion therapy is normovolemia. Placement of a central venous
catheter is strongly recommended to assess central venous pressure, which
should be maintained at approximately 12 mm Hg. As a further method of
ensuring adequate volume status, the urinary output should be monitored with
a Foley catheter and maintained above 1 to 2 ml per kilogram of body weight
per hour.
Anticoagulant Therapy
There is evidence that heparin may be beneficial in the treatment of gas
embolism. Studies have shown that the clinical course of arterial gas
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embolism is less severe if the patient has been treated with heparin before the
embolic event occurs. An argument against heparin therapy is the risk it
entails of hemorrhage into the infarcted tissue. At present, the use of heparin
for the short-term treatment of cerebral arterial gas embolism is not generally
recommended.
Corticosteroid Therapy
The use of corticosteroids in patients with arterial gas embolism remains
controversial. Some authors recommend treatment with corticosteroids to
combat the brain edema that results from gas embolization in the cerebral
arteries. Cerebral gas embolism initially induces the rapid development of
cytotoxic brain edema, with diminished extracellular space and enlarged
intracellular areas. This form of edema does not usually respond to
corticosteroids. Some authors report that corticosteroids aggravate neuronal
ischemic injury after occlusion of the vessels. Corticosteroids may therefore
offer no benefit in patients with gas embolism.
Lidocaine Therapy
Although the results of clinical studies of lidocaine for the treatment of arterial
gas embolism are not yet available, studies in animals suggest that lidocaine
may be beneficial. In animals given prophylactic doses of lidocaine, the
depressant effects of gas embolism on somatosensory evoked potentials and
the elevations in intracranial pressure caused by gas embolism were both
reduced. In a clinical trial, lidocaine provided cerebral protection during
cardiac surgery. Therefore, a strong argument can be made for administering
lidocaine in a bolus dose of 1.5 mg per kilogram and maintaining a therapeutic
concentration, with continuous intravenous administration in patients with
severe arterial gas embolism. However, an overdose of lidocaine may cause
central nervous system depression, cerebral convulsions, and
bradyarrhythmias.
Conclusions
The entry of gas into the venous or arterial system is a risk in virtually all areas
of clinical care. Venous emboli may lead to cardiovascular collapse or to
paradoxical arterial emboli. Arterial emboli may occlude end arteries
throughout the body and may cause serious morbidity or death if they occlude
cardiac or cerebral vessels. Regardless of the mechanism responsible for the
embolism, rapid and aggressive treatment is essential to preserve life and
function. For venous gas embolism, the mainstays of treatment are the
prevention of further entry of gas, volume expansion, the administration of 100
percent oxygen, often with ventilatory support; positive inotropic support; and
cardiopulmonary resuscitation, if necessary. For arterial gas embolism,
hyperbaric oxygen is the treatment of choice, as soon as cardiopulmonary
stabilization has been achieved.
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CHAPTER 14
DEEP VENOUS THROMBOSIS
Introduction
The peripheral venous system functions both as a reservoir to hold extra
blood and as a conduit to return blood from the periphery to the heart and
lungs. Unlike arteries, which possess 3 well-defined layers (a thin intima, a
well-developed muscular media, and a fibrous adventitia), most veins are
composed of a single tissue layer. Only the largest veins possess internal
elastic membranes, and this layer is thin and unevenly distributed, providing
little buttress against high internal pressures. The correct functioning of the
venous system depends on a complex series of valves and pumps that are
individually frail and prone to malfunction, yet the system as a whole performs
remarkably well under extremely adverse conditions.
Primary collecting veins of the lower extremity are passive, thin-walled
reservoirs that are tremendously distensible. Most are suprafascial,
surrounded by loosely bound alveolar and fatty tissue that is easily displaced.
These suprafascial collecting veins can dilate to accommodate large volumes
of blood with little increase in back pressure so that the volume of blood
sequestered within the venous system at any moment can vary by a factor of
2 or more without interfering with the normal function of the veins.
Suprafascial collecting veins belong to the superficial venous system.
Outflow from collecting veins is via secondary conduit veins that have thicker
walls and are less distensible. Most of these veins are subfascial and are
surrounded by tissues that are dense and tightly bound. These subfascial
veins belong to the deep venous system, through which all venous blood must
eventually pass through on its way back to the right atrium of the heart. The
lower limb deep venous system is typically thought of as two separate
systems, one below the knee and one above.
The calf has 3 groups of paired deep veins: the anterior tibial veins, draining
the dorsum of the foot; the posterior tibial veins, draining the sole of the foot;
and the peroneal veins, draining the lateral aspect of the foot. Venous
sinusoids within the calf muscle coalesce to form soleal and gastrocnemius
intramuscular venous plexuses, which join the peroneal veins in the mid calf.
These veins play an important role in the muscle pump function of the
calf. Just below the knee, these tibial veins join to become the popliteal vein,
which too can be paired on occasion.
Together, the calfs muscles and deep vein system form a complex array of
valves and pumps, often referred to as the peripheral heart, that functions to
push blood upward from the feet against gravity. The calf-muscle pump is
analogous to the common hand-pump bulb of a sphygmomanometer filling a
blood pressure cuff. Before pumping has started, the pressure is neutral and
equal everywhere throughout the system and the calf fills with blood, typically
100-150 mL. When the calf contracts, the feeding perforator vein valves are
forced closed and the outflow valves are forced open driving the blood
proximally. When the calf is allowed to relax, the veins and sinusoids refill
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from the superficial venous system via perforating veins, and the outflow valve
is then forced shut, preventing retrograde flow. With each contraction, 40-
60% of the calfs venous volume is driven proximally.
The deep veins of the thigh begin distally with the popliteal vein as it courses
proximally behind the knee and then passes through the adductor canal, at
which point its name changes to the femoral vein. This important deep vein is
sometimes incorrectly referred to as the superficial femoral vein in a
misguided attempt to distinguish it from the profunda femora, or deep femoral
vein, a short, stubby vein that usually has its origin in terminal muscle
tributaries within the deep muscles of the lateral thigh but may communicate
with the popliteal vein in up to 10% of patients. In the proximal thigh, the
femoral vein and the deep femoral vein unite to form the common femoral
vein, which passes upwards above the groin crease to become the iliac vein.
The misleading and incorrect term superficial femoral vein should never be
used because the femoral vein is a deep vein and is not part of the superficial
venous system. The incorrect term does not appear in any definitive anatomic
atlas, yet it has come into common use in vascular laboratory practice.
Confusion arising from use of the inappropriate name has been responsible
for many cases of clinical mismanagement and death.
The external iliac vein is the continuation of the femoral vein as it passes
upward behind the inguinal ligament. At the level of the sacroiliac joint, it
unites with the hypogastric vein to form the common iliac vein. The left
common iliac is longer than the right and more oblique in its course, passing
behind the right common iliac artery. This anatomic asymmetry sometimes
results in compression of the left common iliac vein by the right common iliac
artery to produce May-Thurner syndrome, a left-sided iliac outflow obstruction
with localized adventitial fibrosis and intimal proliferation, often with
associated DVT. At the level of the fifth lumbar vertebra, the 2 common iliac
veins come together at an acute angle to form the inferior vena cava.
Deep venous thrombosis (DVT) most commonly involves the deep veins of
the leg or arm, often resulting in potentially life-threatening emboli to the lungs
or debilitating venous valvular dysfunction and chronic leg swelling. DVT is
one of the most prevalent medical problems and early recognition and
appropriate treatment of complications can save many lives.
Pathophysiology
Over a century ago, Rudolf Virchow described 3 factors that are critically
important in the development of venous thrombosis: (1) venous stasis, (2)
activation of blood coagulation, and (3) vein damage. Over time, refinements
have been made in their description and importance to the development of
venous thrombosis. The origin of venous thrombosis is frequently
multifactorial, with components of the triad of variable importance in individual
patients.
Studies have shown that low flow sites, such as the soleal sinuses, behind
venous valve pockets, and at venous confluences, are at most risk for the
development of venous thrombi. However, stasis alone is not enough to
facilitate the development of venous thrombosis. Experimental ligation of
rabbit jugular veins for periods of up to 60 minutes have failed to consistently
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cause venous thrombosis. Although, patients that are immobilized for long
periods of time seem to be at high risk for the development of venous
thrombosis, an additional stimulus is required to develop deep venous
thrombosis (DVTs).
Mechanical injury to the vein wall appears to provide an added stimulus for
venous thrombosis. Hip arthroplasty patients with the associated femoral vein
manipulation represent a high-risk group that cannot be explained by just
immobilization, with 57% of thrombi originating in the affected femoral vein
rather than the usual site of stasis in the calf. Endothelial injury can convert
the normally antithrombogenic endothelium to become prothrombotic by
stimulating the production of tissue factor, von Willebrand factor, and
fibronectin.
Genetic mutations within the bloods coagulation cascade represent those at
highest risk for the development of venous thrombosis. Primary deficiencies
of coagulation inhibitors antithrombin, protein C, and protein S are associated
with 5-10% of all thrombotic events. Resistance of procoagulant factors to an
intact anticoagulation system has also recently been described with the
recognition of factor V Leiden mutation, representing 10-65% of patients with
deep venous thrombosis (DVT). In the setting of venous stasis, these factors
are allowed to accumulate in thrombosis prone sites, where mechanical
vessel injury has occurred, stimulating the endothelium to become
prothrombotic.
Components of the Virchow triad are of variable importance in individual
patients, but the end result is early thrombus interaction with the endothelium.
This interaction stimulates local cytokine production and facilitates leukocyte
adhesion to the endothelium, both of which promote venous thrombosis.
Depending on the relative balance between activated coagulation and
thrombolysis, thrombus propagation occurs.
Over time, thrombus organization begins with the infiltration of inflammatory
cells into the clot. This results in a fibroelastic intimal thickening at the site of
thrombus attachment in most patients and a fibrous synechiae in up to 11%.
In many patients, this interaction between vessel wall and thrombus leads to
vein wall fibrosis. Histological examination of vein wall remodeling after
venous thrombosis has demonstrated an imbalance in connective tissue
matrix regulation and a loss of regulatory venous contractility that contributes
to the development of chronic venous insufficiency.
Risk factors
Many factors have been identified as known risk factors for the development
of venous thrombosis.
i). The single most powerful risk marker remains a prior history of DVT with up
to 25% of acute venous thrombosis occurring in such patients. Pathologically,
remnants of previous thrombi are often seen within the specimens of new
acute thrombi. However, recurrent thrombosis may actually be the result of
primary hypercoagulable states. Abnormalities within the coagulation cascade
are the direct result of discrete genetic mutations within the coagulation
cascade. Deficiencies of protein C, protein S, or antithrombin III account for
approximately 5-10% of all cases of DVT.
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ii). Age has been well studied as an independent risk factor for venous
thrombosis development. Although a 30-fold increase in incidence is noted
from age 30 to age 80, the effect appears to be multifactorial, with more
thrombogenic risk factors occurring in the elderly than in those younger than
40 years.
iii). Venous stasis, as seen in immobilized patients and paralyzed limbs, also
contributes to the development of venous thrombosis. Autopsy studies parallel
the duration of bed rest to the incidence of venous thrombosis, with 15% of
patients in those studies dying within 7 days of bedrest to greater than 80% in
those dying after 12 weeks. Within stroke patients, DVT is found in 53% of
paralyzed limbs, compared with only 7% on the nonaffected side.
iv). Malignancy is noted in up to 30% of patients with venous thrombosis.
a); The thrombogenic mechanisms involve abnormal coagulation, as
evidenced by 90% of cancer patients having some abnormal coagulation
factors.
b); Chemotherapy may increase the risk of venous thrombosis by affecting the
vascular endothelium, coagulation cascades, and tumor cell lysis. The
incidence has been shown to increase in those patients undergoing longer
courses of therapy for breast cancer, from 4.9% for 12 weeks of treatment to
8.8% for 36 weeks.
c); Additionally, DVT complicates 29% of surgical procedures done for
malignancy.
v). Postoperative venous thrombosis varies depending on a multitude of
patient factors, including the type of surgery undertaken. Without prophylaxis,
general surgery operations typically have an incidence of deep venous
thrombosis (DVT) around 20%, while orthopedic hip surgery can occur in up
to 50% of patients. Based on radioactive labeled fibrinogen, about half of
lower extremity thrombi develop intraoperatively. Perioperative immobilization,
coagulation abnormalities, and venous injury all contribute to the development
of surgical venous thrombosis.
vi). Wells predictive score; A clinical predictive model for DVT. The following
are given a point of 1 if present;
cancer, paralysis or plaster immobilization, bed rest more than 3 days,
surgery in past 4 weeks, localised tenderness, entire leg swollen, calf more
than 3 cm larger than unaffected leg, pitting oedema greter than unaffected
leg, collateral superficial veins.
Alternative diagnosis as likely as or more likely than DVT; -2
Total score of 3 or more = high risk (75%)
score 1-2= moderate risk (17%)
score <1= low risk (3%)
Presentation
DVT is difficult and fraught with uncertainty. The classic signs and symptoms
of DVT are those associated with obstruction to venous drainage and include
pain, tenderness, and unilateral leg swelling. Other associated nonspecific
findings are warmth, erythema, a palpable cord, and pain upon passive
dorsiflexion of the foot (Homan sign). However, even with patients with classic
symptoms, up to 46% have negative venograms. Furthermore, up to 50% of
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those with image-documented venous thrombosis lack any specific symptom.
DVT simply cannot be diagnosed or excluded based on clinical findings; thus,
diagnostic tests must be performed whenever the diagnosis of DVT is being
considered.
When a patient has DVT, symptoms may be present or absent, unilateral or
bilateral, or mild or severe. Thrombus that does not cause a net venous
outflow obstruction is often asymptomatic. Thrombus that involves the iliac
bifurcation, the pelvic veins, or the vena cava produces leg edema that is
usually bilateral rather than unilateral. High partial obstruction often produces
mild bilateral edema that is mistaken for the dependent edema of right-sided
heart failure, fluid overload, or hepatic or renal insufficiency.
Severe venous congestion produces a clinical appearance that can be
indistinguishable from the appearance of cellulitis. Patients with a warm,
swollen, tender leg should be evaluated for both cellulitis and DVT because
patients withDVT often develop a secondary cellulitis, while patients with
primary cellulitis often develop a secondary DVT. Superficial
thrommbophlebitis likewise, is often associated with a clinically inapparent
underlying DVT.
If a patient is thought to have pulmonary embolism (PE) or has documented
PE, the absence of tenderness, erythema, edema, or a palpable cord upon
examination of the lower extremities does not rule out thrombophlebitis, nor
does it imply a source other than a leg vein. More than two thirds of patients
with proven PE lack any clinically evident phlebitis. Nearly one third of
patients with proven PE have no identifiable source of deep venous
thrombosis (DVT), despite a thorough investigation. Autopsy studies suggest
that even when the source is clinically inapparent, it lies undetected within the
deep venous system of the lower extremity and pelvis in 90% of cases.
The criterion standard to diagnostic imaging for DVT remains venography with
pedal vein cannulation, intravenous contrast injection, and serial limb
radiographs. Identification of venous filling defects is diagnostic for venous
thrombosis. However, the invasive nature and significant consumption of
resources are only 2 of its many limitations.
Venous duplex ultrasound has now replaced venography as the diagnostic
study of choice. Its noninvasive nature, wide availability, and minimal
complications are only part of its popularity. A sensitivity and specificity of
97% and 94% on metaanalysis compared with venography have made duplex
ultrasound the imaging of choice for venous thrombosis. Assessment of
venous flow, vein compressibility, and identification of luminal echoes are all
used in the making the diagnosis. However, duplex is limited by operator
experience and body habitus. Other less-used imaging modalities include CT
and MRI, but cost and the need to use intravenous contrast limit its use to
specific clinical indications such as in the diagnosis of May-Thurner syndrome
or thoracic outlet syndrome.
Laboratory analysis has also been used in aiding the diagnosis of venous
thrombosis. D-dimers are degradation products of cross-linked fibrin by
plasmin that are detected by diagnostic assays. Although highly sensitive, up
to 97%, elevated levels are not specific. Many other clinical situations can
123
result in elevated D-dimer levels, including infection, trauma, postoperative
states, and malignancy. Additional blood work should include coagulation
studies to evaluate for a hypercoagulable state, if clinically indicated. A
prolonged prothrombin time or activated partial thromboplastin time does not
imply a lower risk of new thrombosis. Progression of DVT and PE can occur
despite full therapeutic anticoagulation in 13% of patients.
Prevention
Prevention of DVT has long been studied in a variety of clinical situations with
varying degrees of success. Primary prophylaxis is directed toward acting on
one or more components of the Virchow triad, affecting blood flow,
coagulation, or vessel wall endothelium. Studies have also addressed the
timing for the initiation of prophylaxis and the duration.
i). Surgical patients undergoing general anesthesia have been extensively
studied with fatal PE rates ranging from 0.1-0.8% for all patients and up to 7%
of patients undergoing surgery for fractured hips. Many different forms of
therapy have been evaluated in this group. Intermittent pneumatic leg
compression devices work by effectively increasing venous blood flow and
activating the fibrinolytic system. Studies in cardiac surgery and neurosurgical
patients have shown a distinct improvement in the incidence of DVT without
the added risk of bleeding. However, the effect is less impressive in higher-
risk patients, and compliance can be difficult.
ii). Anticoagulants represent another form of primary prophylaxis against
venous thrombosis that has been extensively studies in recent years. The
effectiveness of heparin has been established by numerous randomized
clinical trials. Subcutaneous heparin of 5000 units given twice daily has been
shown to not only decrease the incidence of DVTs but also prevents fatal PE.
iii). Vitamin K antagonists such as warfarin have also been shown to be an
effective form of primary prophylaxis in high-risk patients. Therapy is often
initiated the night prior to surgery; however, the anticoagulation effects of
warfarin do not begin until the third day of use, preventing the propagation of
clinically important thrombosis with less postoperative bleeding complications.
iv). Low-molecular weight heparin (LMWH) has been shown to be superior to
both heparin and warfarin in high-risk patients such as those suffering from
multitrauma and postorthopedic surgery.
v). Timing and duration of prophylactic agents has also been determined to
have a significant effect the development of deep venous thrombosis. Early
prophylaxis in surgical patients with LMWH has been associated with
significant reductions in postoperative venous thrombosis. Studies have
shown that initiation of therapy within 8 hours of surgery has the greatest
effect and is currently recommended by the American College of Chest
Physicians. Additional recommendations by the ACCP for extended out-of-
hospital prophylaxis have been made based on multiple randomized studies
that have demonstrated an additional 7-10 days of anticoagulation decrease
venous thrombosis rates without major bleeding issues.
Medical treatment
The mainstay of medical therapy has been anticoagulation since the
introduction of heparin in the 1930s. Other anticoagulation drugs have
124
subsequently been added to the treatment armamentarium over the years,
such as vitamin K antagonists and low-molecular weight heparin. More
recently, mechanical thrombolysis has become increasingly used as
endovascular therapies have increased. Absolute contraindications to
anticoagulation treatment include intracranial bleeding, severe active
bleeding, recent brain, eye, or spinal cord surgery, and malignant
hypertension. Relative contraindications include recent major surgery, recent
cerebrovascular accident, and severe thrombocytopenia.
Initial anticoagulation therapy traditionally involves continuous intravenous
heparin until adequate systemic anticoagulation is achieved. Rapid
anticoagulation is essential within the first 24 hours of diagnosis, reducing the
incidence of recurrent venous thrombosis during the first 3 months from 25%
to 5%. Continuous intravenous heparin for therapy initiation has been
increasingly replaced by single or twice daily subcutaneous injections of low-
molecular weight heparin (LMWH). LMWH antithrombotic effects correlates
with body weight and permit fixed dosing without laboratory monitoring that
have been shown to be just as effective; it also allows for outpatient treatment
of uncomplicated DVT. However, intravenous heparin remains the treatment
of choice for those with endstage renal failure.
Long-term anticoagulation is necessary to prevent the high frequency of
recurrent venous thrombosis or thromboembolic events. Interruption of
anticoagulation within the first 12 weeks of therapy resulted in a 25%
incidence of recurrent thrombosis. Oral vitamin K antagonists (warfarin)
remain the preferred approach for long-term treatment, which allows for single
dosing oral therapy that can be continued on an outpatient basis.
Warfarin interrupts the production of Vitamin Kdependent coagulation factor
production by the liver. The effect is delayed by 72 hours until the existing
circulating coagulation factors are cleared or used. The initial effect creates a
hypercoagulable state because vitamin Kdependent anticoagulants (protein
C and S) are cleared first from the body while vitamin K dependent
procoagulants continue to circulate. During this period, heparin
anticoagulation is important to prevent worsening thrombosis. INR
maintenance between 2.0 to 3.0 is recommended with higher ratios not
improving effectiveness and lower ratios not reducing bleeding complications.
The duration of therapy with warfarin has been evaluated by multiple
prospective randomized clinical trials. Duration of therapy varies depending
upon patient risk factors and presumed aetiology. First-episode venous
thrombosis or thrombotic event due to a transient reversible risk factor should
be treated for at least 3 months. Interruption of therapy prior to 12 weeks
results in an 8% absolute increase in recurrent thrombosis within the following
12 moths. Treatment for the entire 3 months results in an annual recurrent
DVT incidence of 3%.
For patients with first episode idiopathic venous thrombosis, treatment length
should be 6-12 months. However, the benefit of anticoagulation is lost after
stopping treatment at one year, prompting many physicians to continue
treatment indefinitely. The decision to continue anticoagulation should be
tailored to each patient, taking into consideration bleeding risk and patient
125
preference with treatment reassessment at periodic intervals.
Long-term therapy with LMWH has been shown to be as effective as warfarin
in the treatment of venous thrombosis, except in those patients with a
concurrent malignancy. In this subgroup, LMWH was shown to be more
effective than oral therapy. Initial studies have also shown LMWH to be
effective in pregnant patients.
The main adverse effects of heparin therapy include bleeding and
thrombocytopenia. Approximately 2% of patients experience major bleeding
within the first 3 months of therapy and 1-3% thereafter per year. The
estimated fatality rate for each episode of major bleeding is 13%. The
development of thrombocytopenia must alert clinicians to the diagnosis of
heparin-induced thrombocytopenia (HIT), which can occur in up to 3% of
patients treated with heparin for greater than 4 days. Two types exist; the
most common form is a self-limiting nonimmune mediated thrombocytopenia
that resolves with cessation of therapy. The less common immune-mediated
thrombocytopenia has potentially catastrophic thromboembolic complications.
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CHAPTER 15
PULMONARY AND FAT EMBOLISM

FAT EMBOLISM
Due to fat entering torn venous channels at fracture site.

Chylomicrons may also aggregate due to lipase release.
Presents with pyrexia, tachycardia, tachypnoea, reduced consciousness.
May develop petechial rash.
Clotting may be deranged with features of DIC.
Arterial gases show hypoxia and hypercapnia.
Patients may require ventilation.
Mortality can be as high as 15%.
PULMONARY EMBOLISM
Introduction
Background
Pulmonary embolism (PE) is a common and potentially lethal condition that
can cause death in all age groups.The classic presentation is abrupt onset of
pleuritic chest pain, shortness of breath, and hypoxia.
Under normal conditions, microthrombi (tiny aggregates of red cells, platelets,
and fibrin) are formed and lysed continually within the venous circulatory
system. This ensures maintenance of hemostasis following injury and restricts
uncontrolled propagation of clot. Under pathological conditions, microthrombi
may escape the normal fibrinolytic system to grow and propagate. Pulmonary
embolism (PE) occurs when these propagating clots break loose and
embolize to block pulmonary blood vessels.
Thrombosis in the veins is triggered by Virchows triad: venostasis,
hypercoagulability, and vessel wall inflammation. All known clinical risk factors
for DVT and PE have their basis in one or more elements of the triad.
Patients who have undergone gynecologic surgery, those with major trauma,
and those with indwelling venous catheters may have DVTs that start in an
area related to their pathology. For other patients, venous thrombosis most
often involves the lower extremities and nearly always starts in the calf veins
and propagate proximally to the popliteal veins and embolize to the lungs.
Frequency
Autopsy studies show that an additional equal number of patients are
diagnosed with pulmonary embolism at autopsy, as were initially diagnosed
clinically.
Mortality/Morbidity
(a) Massive pulmonary embolism is defined as presenting with a systolic
arterial pressure less than 90 mm Hg. Accountes for 4-4.5% of the
patients.
(b) Nonmassive pulmonary embolism is defined as having a systolic
arterial pressure greater than or equal to 90 mm Hg. This is the more
common presentation for pulmonary embolism and accounts for 95.5-
96% of the patients.
127
The mortality for patients presenting with massive pulmonary embolism is
between 30% and 60% depending on the study cited. The majority of these
deaths occur in the first 1-2 hours of care.
The diagnosis of massive pulmonary embolism is a function of the size of the
clot and the functional capability of the patient's cardiovascular system.
Hemodynamically stabile pulmonary embolism has a much lower mortality
rate because of treatment with anticoagulant therapy.
In nonmassive pulmonary embolism, the death rate is less than 5% in the first
3-6 months of anticoagulant treatment. The rate of recurrent
thromboembolism is less than 5% in the first 3-6 months. However, recurrent
thromboembolism reaches 30% after 10 years.
Race
Studies looking at the incidence of pulmonary embolism in various races show
that African American patients are the highest risk group, with a 50% higher
incidence than American whites. Asian/Pacific Islanders/American Indian
patients have a markedly lower risk of thromboembolism.
Sex
Across all age groups, there is a fairly equal distribution of initial pulmonary
embolism between males and females. However, most studies find that
women have a significantly lower rate of recurrent pulmonary embolism.
Age
Venous thromboembolism and pulmonary embolism are diseases associated
with advancing age.
History
Diagnosis should be suspected in any patient who presents with any non-
speecific chest symptoms such as chest pain, chest wall tenderness, back
pain, shoulder pain, upper abdominal pain, syncope, hemoptysis, shortness of
breath, painful respiration, new onset of wheezing, any new cardiac
arrhythmia, or any other unexplained symptom referable to the thorax.
The classic triad of signs and symptoms of PE are hemoptysis, dyspnea, and
chest pain but are seen in less than 20% of patients.
Many patients with PE are initially completely asymptomatic, and most of
those who do have symptoms have an atypical presentation.
Other symptoms/signs include seizure, syncope, abdominal pain, high fever,
productive cough, new onset of reactive airway disease, atrial fibrillation,
pleuritic chest pain
Physical findings
Hypotension. Physical examination may also be normal.
After 24-72 hours, loss of pulmonary surfactant often causes atelectasis and
alveolar infiltrates that are indistinguishable from pneumonia on clinical
examination and by radiography, wheezing, pulmonary rub, cyanosis.
Causes
Risk factors for venous thrombosis and pulmonary embolism include:
1. Hereditary factors (most result in a hypercoagulable state)
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
128
Factor V Leiden (most common genetic risk factor for thrombophilia)
Plasminogen abnormality
Plasminogen activator abnormality
Fibrinogen abnormality
Resistance to activated protein C
2. Acquired factors.
The most important clinically identifiable risk factors for DVT and PE
are a prior history of DVT or PE, recent surgery or pregnancy,
prolonged immobilization, or underlying malignancy.
Laboratory Studies
The white blood cell (WBC) count may be normal or elevated. A WBC count
as high as 20,000 is not uncommon in patients with PE.
Clotting study results are normal in most patients with pulmonary
thromboembolism.
D-dimer is a unique degradation product produced by plasmin-mediated
proteolysis of cross-linked fibrin. D-dimer is measured by latex agglutination
or by an enzyme-linked immunosorbent assay (ELISA) and a test result is
considered positive if the level is greater than 500 ng/mL.
Imaging Studies
1. The initial chest radiographic findings are usually normal; sometimes
may show the Westermark sign (ie, a dilatation of the pulmonary
vessels proximal to an embolism along with collapse of distal vessels,
sometimes with a sharp cutoff) and later atelectasis, small pleural
effusion and an elevated hemidiaphragm. After 24-72 hours, one third
of patients develop focal infiltrates indistinguishable from an infectious
pneumonia.
A rare late finding of pulmonary infarction is the Hampton hump, a
triangular or rounded pleural-based infiltrate with the apex pointed
toward the hilum, frequently located adjacent to the diaphragm.
2. High-resolution multidetector computed tomographic angiography
(MDCTA) in patients suspected of having PE.
MDCTA has been shown to have sensitivity and specificity comparable
to that of contrast pulmonary angiography, and, in recent years, has
become accepted both as the preferred primary diagnostic modality
and as the criterion standard for making or excluding the diagnosis of
pulmonary embolism.
3. A positive pulmonary angiogram provides virtually 100% certainty that
an obstruction to pulmonary arterial blood flow does exist. A negative
pulmonary angiogram provides greater than 90% certainty in the
exclusion of PE.
4. Until recently, nuclear scintigraphic ventilation-perfusion (V/Q)
scanning of the lung had been the single most important diagnostic
modality for detecting pulmonary thromboembolism available to the
clinician. Other alternatives were less sensitive, less specific, or
significantly more invasive. Multidetector CT angiography is now a
preferred primary diagnostic modality, but the V/Q scan remains an
129
important part of the evaluation when multidetector CT angiography is
not available or not appropriate for the patient.
5. Duplex ultrasonography
The diagnosis of PE can be proven by demonstrating the presence of a
DVT at any site. Sometimes, this may be accomplished noninvasively,
by using duplex ultrasonography.
A negative ultrasound scan does not rule out DVT, because many
DVTs occur in areas that are inaccessible to ultrasonic examination.
In two thirds of patients with PE, the site of DVT cannot be visualized by
Ultrasound.
6. Other Tests
Electrocardiography
Tachycardia and nonspecific ST-T wave abnormalities.
The classic findings of right heart strain and acute cor pulmonale are
Tall, peaked P waves in lead II (P pulmonale), right axis deviation, right
bundle-branch block, an S 1 Q 3 T 3 pattern, or atrial fibrillation; 20% of
patients with proven PE have any of these classic ECG abnormalities.
Echocardiography or cardiac ultrasonography
Procedures
The primary indication for placement of an inferior vena cava filter in the
setting of pulmonary embolism include contraindications to anticoagulation,
major bleeding complications during anticoagulation, and recurrent
embolization while the patient is receiving adequate therapy.
Treatment
Prehospital Care
Oxygen.
Emergency Department Care
Fibrinolytic therapy has been the standard of care for patients with massive or
unstable pulmonary embolism (PE) since the 1970s. Unless overwhelming
contraindications are evident, a rapidly acting fibrinolytic agent should be
administered immediately to every patient who has suffered hypotension
(even if resolved) or is significantly hypoxemic from PE.
Fibrinolysis also is indicated for patients with PE who have any evidence of
right heart strain, because evidence indicates that the mortality rate can be
cut in half by early fibrinolysis in this patient population.
Today, fibrinolysis may be considered for any patient with PE who lack
specific contraindications to the therapy. Some centers regard fibrinolysis as
the primary treatment of choice for all patients with PE. Interventional
radiology has made it possible to perform transcatheter fibrinolysis for patients
who have DVT without evidence of PE.
Heparin reduces the mortality rate of PE because it slows or prevents clot
progression and reduces the risk of further embolism.
Heparin does nothing to dissolve clot that has developed already, but it is still
the single most important treatment and reduces the overall mortality rate
from 30% to less than 10%.
130
Oxygen should be administered to every patient with suspected PE, even
when the arterial PO2 is perfectly normal, because increased alveolar oxygen
may help to promote pulmonary vascular dilatation.
IV fluids may be beneficial or harmful to the patient who is hypotensive from
PE depending on which point on the Starling curve patient is in;
give a small fluid bolus while monitoring the systolic and diastolic blood
pressures with immediate cessation if the situation worsens after the fluid
bolus.
Improvement or normalization of blood pressure after fluid loading does not
mean the patient has become hemodynamically stable.
Fibrinolysis is indicated for any patient with a PE large enough to cause
hypotension, even if the hypotension is transient or correctable. As noted
above, early fibrinolysis may reduce the mortality rate by 50% for patients who
have right ventricular dysfunction due to PE, even if they are
hemodynamically stable.
Compression stockings
Provide a 30-40 mm Hg compression gradient. Limit or prevent extension of
thrombus. Reduces venous volume by approximately 70% and increases the
measured velocity of blood flow in the deep veins by a factor of 5 or more.
Medication
Immediate full anticoagulation is mandatory for all patients with suspected
deep vein thrombosis (DVT) or pulmonary embolism (PE) because effective
anticoagulation with heparin reduces the mortality rate of PE from 30% to less
than 10%. Heparin works by activating antithrombin III to slow or prevent the
progression of DVT and to reduce the size and frequency of PE. Heparin does
not dissolve existing clot.
Fibrinolytic therapy should be considered in the following group of patients;
1. those who are hemodynamically unstable,
2. those with right heart strain and exhausted cardiopulmonary reserves,
3. those who are expected to have multiple recurrences of pulmonary
thromboembolism over a period of years:Patients with a prior history of
PE and those with known deficiencies of protein C, protein S, or
antithrombin III should be included in this latter group.
Long-term anticoagulation is essential for patients who survive an initial DVT
or PE. The optimum total duration of anticoagulation is controversial but at
least 6 months of anticoagulation is recommended because it is associated
with significant reduction in recurrences and a net positive benefit.
Fibrinolytics
Fibrinolysis is always indicated for hemodynamically unstable patients with
PE, because no other medical therapy can improve acute cor pulmonale
quickly enough to save the patient's life.
Because it is less invasive and has fewer complications, fibrinolytic therapy
has replaced surgical embolectomy as the primary mode of treatment for
hemodynamically unstable patients with pulmonary thromboembolism.
Surgical thromboembolectomy now is reserved for patients in whom
fibrinolysis has failed or cannot be tolerated.
131
Fibrinolytic regimens currently in common use for PE include 2 forms of
recombinant tissue plasminogen activator, t-PA (alteplase) and r-PA
(reteplase), along with urokinase and streptokinase. Alteplase usually is given
as a front-loaded infusion over 90 or 120 minutes. Urokinase and
streptokinase usually are given as infusions over 24 hours or more. Reteplase
is a new-generation thrombolytic with a longer half-life that is given as a single
bolus or as 2 boluses administered 30 minutes apart.
Of the 4, the faster-acting agents reteplase and alteplase are preferred for
patients with PE, because the condition of patients with PE can deteriorate
extremely rapidly.
Streptokinase is least desirable of all the fibrinolytic agents because antigenic
problems and other adverse reactions force the cessation of therapy in a large
number of cases.
Empiric thrombolysis may be indicated in selected hemodynamically unstable
patients, particularly when the clinical likelihood of PE is overwhelming and
the patient's condition is deteriorating. The overall risk of severe complications
from thrombolysis is low and the potential benefit in a deteriorating patient
with PE is high. Empiric therapy especially is indicated when a patient is
compromised so severely that he or she will not survive long enough to obtain
a confirmatory study. Empiric thrombolysis should be reserved, however, for
cases that truly meet these definitions, as many other clinical entities
(including aortic dissection) may masquerade as PE, yet may not benefit from
thrombolysis in any way.
If indicated, fibrinolysis may be used in pregnancy at the same dose used for
nonpregnant patients. Fear of complications should not prevent the use of
fibrinolytics when a pregnant patient has significant right ventricular
dysfunction from PE, as the best predictor of fetal outcome in this setting
remains maternal outcome.
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CHAPTER 16
COMPARTMENT SYNDROME
Limb compartments:
The deep fascia envelops the limbs
Other fascial planes divide the limbs into compartments
The forearm has two compartments
The thigh has three compartments
The lower leg therefore has four compartments
Compartment syndrome
A condition in which the circulation and function of tissues within a closed
space is compromised by an increase in pressure within that space
Pathophysiology
The normal lower limb venous pressure is a few mmHg
Normal intracompartmental pressures are in the range 0 - 10 mmHg
Compartmental pressure does not interfere with blood flow.
Swelling within a facial compartment results in increased intracompartmental
pressure.
Initial venous compromise may progress to reduced capillary flow.
This exacerbates the ischaemic insult and further increases pressure.
A vicious cycle of increasing pressures can be initiated.
Arterial inflow rarely reduced unless pressure exceed systolic blood pressure
Irreversible muscle ischaemia will occur within 6 to 12 hours
Surgical treatment within 6 hours of onset usually results in a positive
outcome.
Aetiology
Orthopaedic:
Tibial fractures (especially comminuted fractures)
Forearm fractures
Vascular:
Ischaemia-reperfusion injury
Haemorrhage
Phlegmasia caerulea dolens
Iatrogenic:
Vascular puncture in anticoagulated patients
Intravenous or intra-arterial drug injection
Soft-tissue injury:
Prolonged limb compression
Crush injury
Burns
Clinical features
Compartment syndromes are normally seen with 48 hours of injury
Typical clinical features include:
Increasing pain despite immobilisation of fracture
133
Altered sensation in the distribution of nerves passing through the
compartment
Muscle tenderness
Excessive pain on passive movement
Peripheral pulses may still be present
Pressure monitoring
Intracompartmental pressure (ICP) can be measured by several means
including: Wick catheter, simple needle manometry, infusion techniques,
pressure transducers, side-ported needles.
Critical pressure for diagnosing compartment syndrome unclear.
Different authors consider surgical intervention if:
Absolute ICP greater than 30 mmHg
Difference between diastolic pressure and ICP greater than 30 mmHg
Difference between mean arterial pressure and ICP greater than 40 mmHg
Treatment
Remove constricting casts, splints etc
Casts should be split on both sides and constricting dressings or padding cut
If no improvement prompt fasciotomies required.
Need to divide skin and deep fascia for the whole length of the compartment
Wounds should be left open
May require delayed closure or skin grafting
Fasciotomies:
Several surgical approaches have been described
The goal is prevention of disability
Decompression should not be compromised by a desire for good cosmesis
All compartments should be decompressed
Two incision required to decompress the 4 compartments of the lower leg
Skin incisions of about 15-20 cm in length are required
Outcome
Timely surgery produces a good functional outcome.
Delay results in muscle ischaemia and necrosis.
Muscle fibrosis produces the typical Volkmann's ischaemic contracture.
134
CHAPTER 17
BLEEDING IN THE SURGICAL PATIENT.
DISORDERS OF COAGULATION AND HAEMOSTASIS

The haemostatic response has three elements: vasoconstriction, platelet
aggregation, clotting cascade.
Vasoconstriction; occurs as a direct result of vessel injury. It is enhanced by
vasoconstricting elements released from platelets.
Pain can also result in reflex sympathetic vasoconstriction
Platelet aggregation; Platelets are formed in bone marrow from
megakaryocytes. Contain the contractile proteins actin and myosin
No nucleus but contain endoplasmic reticulum and Golgi apparatus that can
produce proteins and mitochondria that can produce ATP and ADP
Clotting cascade
The clotting cascade has two semi-independent pathways
The intrinsic pathway has all of its components within blood
The extrinsic pathway is triggered by extravascular tissue damage
This pathway is activated by exposure to a tissue factor
Both pathways result in activation of prothrombin (factor II)
The final common pathway converts fibrinogen to fibrin monomer
Polymerisation of fibrin results in the formation of long fine strands held
together by H-bonds
These are then converted into covalent bonds with stabilisation of the fibrin
polymer
The intrinsic path ways is relatively slow (2-6 minutes)
The extrinsic pathways is quite fast (15 seconds)
Classification of bleeding disorders.
Bleeding disorders can arise from disorders of the: vessel wall, Platelets, and
coagulation system
1. Vessel wall
Hereditary haemorrhagic telangiectasia, Ehlers-Danlos syndrome,
drugs (e.g. steroids), sepsis, trauma, vasculitis
2. Platelets
Congenital platelet disorders, Thrombocytopenia, Myeloproliferative
disorders, Drugs (e.g. aspirin).
3. Coagulation system
Haemophilia A, B, Von Willebrand disease, Factor IX, XIII deficiency, Liver
disease, Anticoagulants, Disseminated intravascular coagulation
Coagulation tests:
1. Prothrombin time (PT)
Tests extrinsic and common pathways
Thromboplastin and calcium are added to patient plasma
PT is expressed as ratio INR (International Normalised Ratio = INR)
Prolonged in:
Warfarin treatment
Liver disease
135
Vitamin K deficiency
Disseminated intravascular coagulation
2. Activated partial thromboplastin time (APPT, KCCT)
Tests intrinsic and common pathways
Kaolin added to patient plasma
Prolonged in:
Heparin treatment
Haemophilia and factor deficiencies
Liver disease
Massive transfusion
Lupus anticoagulant
3. Thrombin time (TT)
Tests common pathway
Thrombin added to patient plasma
Converts fibrinogen into fibrin
Prolonged in:
Heparin treatment
Dysfibrinogenaemia
4. Bleeding time (BT)
Measures capillary bleeding
Prolonged in:
Platelet disorders
Vessel wall disorders
Haemophilia
Haemophilia A is due to factor VIII deficiency
Haemophilia B (Christmas disease) is due to factor IX deficiency
Haemophilia A
Affects about 1 in 10,000 population
It is a sex-linked clotting disorder
One-third of patients have no family history
Usually presents in childhood with:
Prolonged haemorrhage after dental extraction/circumcision,
Recurrent haemarthroses or muscle haematomas.
Sub-periosteal haematomas can result in haemophilic pseudo-tumours
Clinical severity depends on extent clotting factor deficiency
<1% activity - severe disease with life-threatening bleeding
1-5% activity - moderate disease with post-traumatic bleeding
5-20% activity - mild disease
Investigation
Activated partial thromboplastin time (APPT) is prolonged
prothrombin time (PT) is normal
Whole blood coagulation time is prolonged
Factor VIII is reduced
Treatment
136
Bleeding episodes are treated with factor VIII replacement
Given as either factor VIII concentrate or cryoprecipitate
Bleeding usually well controlled if factor VIII levels raised above 20% normal
Desmopressin increases intrinsic factor VIII levels
5-10% develop antibodies to factor VIII
Renders patients refractory to factor replacement therapy

Due to widespread intravascular activation of clotting cascade
Causes a bleeding tendency due to consumption of clotting factors
Presents with bruising or purpura
Oozing from surgical wounds and venepuncture sites
Causes
Severe (usually gram-negative or meningococcal) infection
Widespread mucin-secreting metastatic adenocarcinoma
Hypovolaemic shock
Burns
Transfusion reactions
Eclampsia
Amniotic fluid embolus
Promyelocytic leukaemia
Investigation
Increased KPPT and PT
Reduced serum fibrinogen levels (<1 mg / ml)
Thrombocytopenia
Increased fibrin degradation products
Factor V and VIII activities are reduced
Treatment
Fluid resuscitation
Treat underlying cause
Correct clotting abnormalities with:
Fresh frozen plasma
Cryoprecipitate
Platelet transfusion
Recombinant Factor VIIa
Factor VIIa is a trypsin-like serine protease
Its is an initiator of thrombin generation
Acts via two pathways to activate Factor Xa
One pathway is at the site of tissue injury complexed with Tissue Factor
The other pathway is on the platelet surface independent of Tissue Factor
Tissue factor is found in the subendothelial layer of the vascular wall
Not normally available to complex with Factor VIIa
Following injury subendothelial layer is exposed and tissue factor can bind to
Factor VIIIa
Theoretically both mechanisms localises action of Factor VIIa to the site of
trauma
Clinical uses
137
Licensed for use in haemophiliacs with antibodies to Factor VIII
May have use in trauma patients with massive blood loss
Reduces visible coagulopathic haemorrhage
Significantly reduces blood transfusion requirements in patients with blunt
trauma
May also reduce incidence of MOF and ARDS in trauma patients
Have a half-life in the blood of 8-12 days
In response to tissue damage platelets undergo a number of changes
Platelet aggregation can result in a 'platelet plug' that can block a small hole
Platelets adhere to damaged endothelium (via Von Willebrand factor)
Aggregating platelets releases arachadonic acid, converted to thromboxane
A2
Calcium mediated contraction of actin and myosin results in degranulation
Releases ADP which can induces further aggregation and release in a
positive feedback fashion
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CHAPTER 18
BLOOD & BLOOD PRODUCTS.
The indications for transfusion in surgical practice are as follows.

1. Following traumatic incidents where there has been severe blood loss,
or haemorrhage from pathological lesions, for example from the
gastrointestinal tract.
2. During major operative procedures where a certain amount of blood
loss is inevitable, for example abdominoperineal or cardiovascular
surgery.
3. Following severe burns where, despite initial fluid and protein
replacement, there may be associated haemolysis.
4. Postoperatively in a patient who has become severely anaemic.
5. Preoperatively, usually in the form of packed cells given slowly (see
Blood fractions and Complications, later) in cases of chronic anaemia
where surgery is indicated urgently, i.e. where there is inadequate time
for effective iron or other replacement therapy, or where the anaemia is
unresponsive to therapy, for example aplastic anaemia.
6. To arrest haemorrhage or as a prophylactic measure prior to surgery,
in a patient with a haemorrhagic state such as thrombocytopenia,
haemophilia or liver disease (see Blood fractions, later).
Preparation of blood products for transfusion

It is important that blood donors should be fit and with no evidence of infection
especially hepatitis and human immunodeficiency virus (HIV) infection.
Blood is collected into a sterile commercially prepared plastic bag with needle
and plastic tube attached in a complete, closed sterile unit.
With the donor lying on a couch, a sphygmomanometer cuff is applied to the
upper arm and inflated to a pressure of 70 mmHg (9.3 kPa) or 80 mmHg (10.6
kPa). After introducing 0.5 ml of local anaesthetic, a 15G needle is introduced
into the median cubital vein and 410 ml of blood allowed to run into the bag
containing 75 ml of anticoagulant solution (CPD citrate potassium
dextrose).
During collection, the blood is constantly mixed with the anticoagulant to
prevent clotting, and at the end of the procedure the tube is clamped and the
needle removed. Specimens for use in blood grouping and cross-matching
procedures may be obtained by clamping off small sections of the plastic
tubing containing the donor blood.
Blood storage
All blood for transfusion must be stored in special blood bank refrigerators
controlled at 40C 20C. Blood allowed to stand at higher temperatures for
more than 2 hours is in danger of transmitting infection.
CPD blood has a shelf-life of 3 weeks. The red blood cells, or erythrocytes,
suffer a temporary reduction (2472 hours) in their ability to release oxygen
to the tissues of the recipient, so if a patient requires an urgent and massive
transfusion it is wise to give 1 or 2 units of blood which are less than 7 days
139
old.
White blood cells
White blood cells are rapidly destroyed in stored blood.
Platelets
At 40C the survival of platelets is considerably reduced, and few are
functionally useful after 24 hours. Platelets which are separated show good
survival even after 72 hours.
Clotting factors
Like platelets, clotting factors VIII and V are labile and their levels fall quickly.
Blood fractions
Whole blood may be divided into various fractions. This is not only more
economical of blood donors, but certain fractions are more appropriate than
whole blood transfusion for certain clinical conditions. Fractionation
procedures are relatively safe and simple, using sealed sterile plastic bag
units.
Packed red cells
Packed red cells are especially advisable in patients with chronic anaemia, in
the elderly, in small children and in patients in whom introduction of large
volumes of fluid may cause cardiac failure. Packed red cells are suitable for
most forms of transfusion therapy, including major surgery, especially in
association with clear fluids. Good packing can be obtained by letting the
blood sediment and removing the plasma, or by centrifugation of whole blood.
Platelet-rich plasma
Platelet-rich plasma is suitable for transfusions to patients with
thrombocytopenia who are either bleeding or require surgery.
Platelet concentrate
Platelet concentrate for transfusion to patients with thrombocytopenia is
prepared by centrifugation of platelet rich plasma.
Plasma
This is removed after centrifugation of whole blood and it may be further
processed or fractionated in various ways.
Human albumin 4.5 per cent.
Repeated fractionation of plasma by organic liquids followed by heat
treatment results in this plasma fraction, which is rich in protein but free from
the danger of transmission of serum hepatitis. This may be stored for several
months in liquid form at 40C and is suitable for replacement of protein, for
example following severe burns.
Fresh frozen plasma.
Plasma removed from fresh blood obtained within 4 hours is rapidly frozen by
immersing in a solid carbon dioxide and ethyl alcohol mixture. This is stored at
400C and is a good source of all the coagulation factors. It is the treatment
of choice when considering surgery in patients with abnormal coagulation due
to severe liver failure. It may also be given in any of the congenital clotting
factor deficiency diseases in their milder forms, especially Christmas disease
(Factor IX deficiency) or haemophilia (Factor VIII deficiency).
Cryoprecipitate.
140
When fresh frozen plasma is allowed to thaw at 40C a white glutinous
precipitate remains and, if the supernatant plasma is removed, this
cryoprecipitate is a very rich source of Factor VIII. It is stored at 400C and is
immediately available for treatment of patients with haemophilia (Factor VIII
deficiency). The advantage of cryoprecipitate treatment in haemophilia is the
simplicity of administering large quantities of Factor VIII in relatively small
volumes by intravenous injection. It is also a rich source of fibrinogen, of value
in hypofibrinogenaemic states.
Factor VIII concentrate and Factor IX concentrate.
Factor VIII concentrate and Factor IX concentrate are stored in freeze-dried
form.
Fibrinogen.
Fibrinogen is prepared by organic liquid fractionation of plasma and stored in
the dried form. When reconstituted with distilled water, it is used in patients
with severe depletion of fibrinogen (e.g. disseminated neurovascular
coagulation or congenital afibrinogenaemia). It does, however, carry a high
risk of hepatitis.
Blood grouping and cross-matching
Human red cells have on the cell surface many different antigens. For
practical purposes, there are two groups of antigens which are of major
importance in surgical practice:
antigens of the ABO blood groups and antigens of the rhesus (Rh) blood
groups.
Antigens of the ABO blood groups
These are strongly antigenic and are associated with naturally occurring
antibodies in the serum. Individuals show four different ABO cell groups.
Antigens of the rhesus blood groups
The antigen of major importance in this group is Rh(D), which is strongly
antigenic and is present in approximately 85 per cent of the population in the
UK. Antibodies to the D antigen are not naturally present in the serum of the
remaining 15 per cent of individuals, but their formation may be stimulated by
the transfusion of Rh-positive red cells. Such acquired antibodies are capable,
during pregnancy, of crossing the placenta and, if present in a Rh-negative
mother, may cause severe haemolytic anaemia and even death (hydrops
fetalis) in a Rh-positive fetus in utero. The other minor blood group antigens
may be associated with naturally occurring antibodies, or may stimulate the
formation of antibodies on relatively rare occasions.
Incompatibility
If antibodies present in the recipients serum are incompatible with the donors
cells, a transfusion reaction will result. This is the result of agglutination and
haemolysis of the donated cells leading in severe cases to acute renal tubular
necrosis and renal failure. For this reason, therefore, it is essential that all
transfusion should be preceded by:
1. ABO and rhesus grouping of the recipients and donors cells so that
only ABO and Rh(D) compatible blood is given;
2. direct matching of the recipients serum with the donors cells to
confirm ABO compatibility and to test for rhesus and any other blood
141
group antibody present in the serum of the recipient.
Blood grouping and cross-matching require full laboratory procedures
and take 1 hour. In emergencies it may be necessary to reduce this
time, but the risk of doing this must be weighed against the danger to
the patient by the delay in transfusion entailed by the full procedures. In
such emergencies, it may be advisable to restore the patients blood
volume by saline, gelatin (e.g. Haemaccel), dextran or human albumin
4.5 per cent until blood has been made available. Alternatively, donor
blood, group 0-negative, which is compatible with the majority of
individuals, should be given and this should always be available in
acute emergency situations.
Giving blood
Blood transfusion is commenced by:
1. selection and preparation of the site;
2. careful checking of the donor blood: this should bear a compatibility
label stating the patients name, hospital reference number, ward
and blood group;
3. insertion of the needle or cannula the latter may be valuable if
intravenous therapy is required for any length of time;
4. giving detailed written instructions as to the rate of flow, for example
40 drops/mm allows one 540 ml unit of blood to be transfused in 4
hours.
In acute emergencies, it may be necessary to increase the rate of
flow and it is possible to give 12 units in 30 minutes using a
pressure cuff around a plastic bag of blood.
Warming blood. During cardiopulmonary operations, the blood must be
warmed before reaching the patient by passing it through a carefully
temperature-regulated blood warming unit, thus reducing the risk of cardiac
arrest from large volumes of cold blood direct from the refrigerator.
Filtering blood. A filter with an absolute filtration rating of 40 micron will filter
off platelet aggregates and leucocytes membranes in stored blood.
Autotrans fusion
This is an old, well-tried method of immediately restoring a patients blood
volume, by transfusion with his or her own blood. In an emergency, for
example, in a case of ruptured ectopic gestation, the blood is collected from
the peritoneal cavity and put into a sterile container suitable for connecting to
transfusion tubing. The classical method of filtration of this blood to prevent
the transfusion of any small clots is to place a piece of sterile gauze within the
container. Nowadays, special autotransfusion apparatus is being marketed.
For major elective procedures, the patient may donate his or her own blood,
withdrawal and storage taking place up to 3 weeks before it is required.
Natural blood volume and most of the red cell recovery will have taken place
in that time.
Complications of blood transfusion
1. Congestive cardiac failure
This is especially liable to occur in the elderly or where there is
cardiovascular insufficiency, and may result from too rapid infusion of
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large volumes of blood. It is advisable in the individual with chronic
anaemia to give packed red cells and, at the same time, give diuretic
drugs. The transfusion should be given slowly, i.e. I unit over 46
hours and, if necessary, on two separate occasions.
2. Transfusion reactions
These may be the result of the following problems:
i). Incompatibility. This should be avoided if the correct procedures of
grouping and cross-matching have been adopted but, in fact, it is
nearly always due to human error in the collection, labelling or
checking of the specimens and donor bags. The patient develops a
rigor, temperature and pain in the loins, and may become extremely
alarmed. The transfusion should be stopped immediately, and a fresh
specimen of venous blood and urine from the patient sent together with
the residue of all the used units of donor blood to the laboratory for
checking.
A close watch should be kept on the patients pulse, blood pressure
and urinary output. Frusemide 80120 mg i.v. should be given to
provoke a diuresis, and repeated if the urine output falls below 30
ml/hour. Dialysis may be necessary.
ii). Simple pyrexial reactions in which the patient develops pyrexia,
rigor and some increase in pulse rate. These are the result of
pyrogens in the donor apparatus and are largely avoided by the use of
plastic disposable giving sets.
iii). Allergic reactions in which the patient develops mild tachycardia
and an urticarial rash; rarely an acute anaphylactic reaction may occur.
This is the result of allergic reaction to plasma products in the donor
blood. The reaction is treated by stopping the transfusion and giving an
antihistamine drug (chlorpheniramine 10 mg or diphenhydrazine 25
mg).
iv). Sensitisation to leucocytes and platelets. This is not uncommon in
those patients who have received many transfusions in the past, for
example for thalassaemia, refractory anaemia or aplastic anaemia. The
individual develops antibodies to donated white cells or platelets, which
cause reactions with each transfusion. They may be minimised by
giving packed red cells from which plasma and huffy coat layers have
been removed or by washing of donor cells. Aspirin, antihistamines or
steroids may also be given to the recipient if necessary.
v). Immunological sensitisation. Only the ABO, Kell and Rh(D) groups
are considered for blood transfusion. Immune antibodies may be
stimulated by transfusion, and may give rise to difficulties with
compatibility tests or to haemolytic transfusion reactions.
3. Infections
There are four main reasons for blood transfusion causing infection in
the recipient.
i). Serum hepatitis virus may be transmitted from the donor and is
usually a severe hepatitis arising approximately 3 months after the
transfusion. It should be avoided by adequate verbal screening of the
143
blood donor and by testing for the presence of the hepatitis associated
antigen in the blood prior to transfusion.
ii). HIV infection can be transmitted by blood and blood products. All
donors must be screened. Haemophiliacs are at special risk because
of their more frequent requirements for blood products.
iii). Bacterial infection may result from faulty storage. This arises most
commonly from the donor blood being left in a warm room for some
hours before the transfusion is commenced. This allows proliferation of
any bacteria, and transfusion of such infected blood may result in
severe septicaemia in the recipient and rapid death.
iv). Malaria can be transmitted by blood transfusion in areas where the
disease is endemic. The patient should be given prophylactic
antimalarial drugs.
4. Thrombo phlebitis
5. Air embolism
6. Coagulation failure
Coagulation failure is due to:
i). dilution of clotting factors/platelets due to large volumes of stored
blood being used to replace losses as stored blood is low in platelets,
Factor VIII and Factor V;
ii). disseminated intravascular coagulation (DIC) following an
incompatible blood transfusion, particularly ABO incompatibility. The
further haemorrhage may be treated by replacement of the deficient
factors (usually fibrinogen, Factors VIII, V and II, and platelets), with
fresh frozen plasma, cryoprecipitate and platelet concentrates.
Paradoxically, heparin may be used sometimes for the treatment of
DIC.
Haemophilia and the congenital haemorrhagic diseases
Haemophilia
Haemophilia (haemophilia A) is a haemorrhagic diathesis caused by
the congenital deficiency in the blood of Factor VIII [antihaemophilic
globulin (AHG)]. It is a sex-linked characteristic, transmitted by the
asymptomatic female carriers, and manifest only in males.
The levels of Factor VIII in the blood of severe haemophiliacs may be
less than 1 percent of the average normal level. In the case of
spontaneous haemorrhage (e.g. into joints) treatment should aim at
raising the level to at least 20 per cent. Should surgery be anticipated
in the haemophiliac, the level should be raised to 50100 per cent.
Factor VIII concentrates are superseding cryoprecipitates. The amount
of either preparation depends on the problem and the level required for
haemostasis, i.e. more for surgery than for a haemarthrosis. Frequent
monitoring of the Factor VIII level will be necessary in cases involving
surgery.
Additional forms of therapy may include fresh blood, if necessary for
blood loss, fresh frozen plasma or, more rarely, dried concentrates of
animal AHG (see also AIDS).
Christmas disease
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Christmas disease (haemophilia B) is a congenital disease resulting
from the deficiency of Factor IX (Christmas factor). Clinically, the
manifestations of the disease are similar to haemophilia. Factor IX is
replaced by the transfusion of fresh frozen plasma, or by reconstituted
dried concentrates of human Factor IX.
Haemophilic joints
In both haemophilia and Christmas disease, haemorrhage into joints is
very common, and persistent and recurrent haemarthrosis may result
in permanent damage to the articular surfaces and disorganisation of
the joint. The most important feature of treatment is that it should be
prompt. Replacement of the clotting factor should be instituted
immediately and before severe tension is allowed to build up in the
joint.
Von Willebrands disease
Von Willebrands disease, with episodic bleeding manifestations, is a
type of haemorrhagic disease, with low plasma levels of both Factor
VIII complement and Factor VIII related antigen, and platelet
abnormalities.
Sickle-cell disorders
Sickle-cell disorders can be a serious problem in surgery, especially
with children. All patients from certain parts of Kenya (coast and
Nyanza) should be screened for the presence of sickle haemoglobin. In
sickle-cell trait (HbA +5) care to avoid hypoxia during anaesthesia is
important. In sickle-cell anaemia, a preoperative partial exchange
transfusion of packed cells to reduce the haemoglobin S level to less
than 30 percent may be required, depending on the procedure and the
length of the operation. Oxygen is given for the prevention of hypoxia;
hypothermia and dehydration must be strenuously avoided. Spinal
anaesthesia and tourniquets are contraindicated. Pigments gallstone
formation is common.
Blood substitutes albumin, dextran, gelatin
One of the most urgent requirements in a patient suffering from acute
blood loss is the re-establishment of a normal blood volume. This may
be achieved satisfactorily with a number of plasma substitutes.
Human albumin 4.5 per cent has superseded the use of dried plasma
and can be used whilst cross-matching is being performed. Two to
three units (1.2 litres) are given intravenously over 30 minutes. It is
valuable in patients with burns where there has been severe loss of
protein. There is no risk of transmitting hepatitis.
Dextrans are polysaccharide polymers of varying molecular weight
producing an osmotic pressure similar to that of plasma. They have the
disadvantage of inducing rouleaux of the red cells and this interferes
with blood-grouping and cross-matching procedures, hence the need
for a blood sample beforehand. Dextrans interfere with platelet function
and may be associated with abnormal bleeding, and for this reason it is
recommended that the total volume of dextran should not exceed 1000
ml.
145
Low-molecular-weight dext ran (dextran 40, Rheomacrodex) has an
immediate effect in a restoring plasma volume, but it is transitory
because the small molecules are readily excreted by the kidney. It may
be useful in preventing sludging of red cells in small blood vessels, for
example of the kidney, and thus preventing the renal shutdown
associated with severe hypotension. It is less likely to induce rouleaux
formation than the high-molecular-weight compounds.
The high-molecular-weight dextrans (dextran 110 and dextran 70) are
less effective in the early phase of hypovolaemia but are longer acting
as they are retained for some time within the circulation.
Gelatin in a degraded form (molecular weight around30 000) is used
increasingly as a plasma expander. Up to1000 ml of a 3.44 per cent
solution (containing anions andcations) is given intravenously (e.g.
Haemaccel, Gelafusine).
SUMMARY
ABO system
Consists of three allelic genes - A, B and O
A and B genes control synthesis of enzymes that add carbohydrate residues
to cell surface glycoproteins
The O gene is an amorph and does not transform the glycoprotein
Six possible genotypes but only four phenotypes
Naturally occurring antibodies are found in the serum of those lacking the
corresponding antigen.
ABO blood group system
Phenotype Genotype Antigens Antibodies Frequency (%)
O OO O Anti-A, Anti-B 46
A AA or AO A Anti-B 42
B BB or BO B Anti-A 9
AB AB AB None 3
Blood group O = universal donor

Blood group AB = universal recipient
Rhesus system
Rhesus antibodies are immune antibodies requiring exposure during
transfusion or pregnancy
85% population are rhesus positive
90% of Rh-negative patients transfused with Rh-positive blood develop anti-D
antibodies
Cross Matching
Blood grouping
Patients red cells grouped for ABO and Rhesus antigens
Serum tested to confirm patients ABO group
Antibody screening
Detects atypical red cell antibodies in recipients serum
Crossmatching
Tests donor red cells against patients serum
146
Complications of blood transfusion
Early
Haemolytic reactions (immediate or delayed)
Bacterial infections from contamination
Allergic reactions to white cells or platelets
Pyogenic reactions
Circulatory overload
Air embolism
Thrombophlebitis
Citrate toxicity
Hyperkalaemia
Clotting abnormalities
Late
Infection - cytomegalovirus / hepatitis
Immune sensitisation
Iron overload
Acute haemolytic or bacterial transfusion reactions
Due to acute haemolysis or bacterial contamination
Difficult to differentiate on clinical grounds
May occur after infusion of small volume of incompatible or infected blood
Associated with high morbidity and mortality
In unconscious patient bleeding due to DIC may be only sign
Most ABO mismatched transfusions are due to human error
Usually occurs soon after start of transfusion
Patient feels unwell and agitated
Symptoms include back pain and pain at infusion site
Associated with shortness of breath, rigors
Examination will show hypotension, oliguria and bleeding from venepuncture
sites
Urinalysis will show haemoglobinuria
Management
Discontinue transfusion immediately and remove giving set
Check unit of blood against patients identity
Give intravenous crystalloid
Consider transfer to the intensive care unit
Take blood for FBC, plasma haemoglobin, clotting, blood cultures and repeat
grouping
Give broad spectrum antibiotics
Monitor urine output and ECG
Anaphylaxis
Usually occurs soon after start of transfusion
May be seen in IgA deficient patients reacting to transfused IgA
Presents with circulatory collapse and bronchospasm
Management
Discontinue transfusion and remove giving set
Maintain airway and give oxygen
Administer adrenaline, chlorpheniramine, salbutamol
147
If the patient is IgA deficient any further transfusion must be carefully planned
Non-haemolytic transfusion febrile reaction
Usually occurs more than 30 minutes after start of transfusion
Patient feels generally well but may be shivering
Temperature is usually less than 38.5 C
Blood pressure is usually normal
Management
Stop transfusion and assess possibility that this may be a more significant
reaction
Restart transfusion at a slower rate
Consider the use of paracetamol
Hydrocortisone should not be routinely used during a transfusion
Transfusion related acute lung injury
Occurs following administration of plasma-containing blood components
Due to interaction of donor antibodies with recipient white cells
The clinical pictures is similar to ARDS
Occurs 30 minutes to several days after transfusion
Clinical features include fever, cough and shortness of breath
Chest x-ray shows perihilar shadowing
Treat as ARDS
Delayed haemolytic transfusion reaction
Occurs 5-10 days after transfusion
Clinical features are usually minimal
Possibly unexplained pyrexia or jaundice
Unexplained drop in haemoglobin
Urinalysis shows urobilinogenuria
Management
Check LFTs, clotting and red cell antibody screen
Autologous transfusion
Is the use of the patients own blood
Particularly useful in elective surgery
Accounts for 5% of transfusions in USA
Reduces the need for allogeneic blood transfusion
Reduces risk of postoperative complications (e.g. infection, tumour
recurrence)
Three main techniques are:
Predeposit transfusion
Intraoperative acute normovolaemic haemodilution
Intraoperative cell salvage
Predeposit transfusion
Blood collection begins 3-5 weeks preoperatively
Between 2 and 4 units are often stored
Last unit collected more than 72 hours preoperatively
Eliminates the risk of viral transmission
Reduces the risk of immunological transfusion reactions
Reduces risk of postoperative immunosuppression seen with allogeneic
transfusion
148
Collection is expensive and time-consuming
Only suitable for elective surgery
Intraoperative acute normovolaemic haemodilution
Whole blood is removed at start of operative procedure
Between 1.0 and 1.5 litres can be collected
Replaced with crystalloid or colloid solution
Few detrimental effects of acute anaemia have been demonstrated
Blood is stored in theatre at room temperature
Blood is re-infused during or immediately following surgery
Cheaper than predeposit transfusion
Little risk of administrative or clerical error
Suitable for elective or emergency surgery at which considerable blood loss
anticipated
Intraoperative cell salvage
Shed blood is collected from operative field
Blood is anticoagulated with citrate or heparin and filtered to remove debris
and clots
Cells are then washed with saline and concentrated by centrifugation
Concentrate is then reinfused
Large volumes of blood can be salvaged
Salvaged blood is not haemostatically intact
Platelets and clotting factors are consumed
Suitable in cardiac or trauma surgery
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CHAPTER 19
SEPTIC SHOCK. SIRS. MODS. ARDS.
Septic shock is the most common cause of mortality in the intensive care unit.
Despite aggressive treatment mortality ranges from 15% in patients with
sepsis to 40-60% in patients with septic shock. There is a continuum of
clinical manifestations from systemic inflammatory response syndrome
(SIRS) to sepsis to severe sepsis to septic shock to Multiple Organ
Dysfunction Syndrome (MODS).
Viruses and fungi can cause septic shock. Bacterial infections are the most
common cause of septic shock. Almost any bacterium can cause bacteremia.
Bacteremia is not necessary for the development of septic shock. Only 30-50
percent of patients with sepsis have positive blood culture results.
Pediatric septicaemia: sepsis in children from infection with S. pneumonia,
Neisseria meningitides, S aureus. H influenza can be a cause of sepsis if child
not vaccinated with Hib vaccine. Sepsis in the neonate is most likely to be
caused by S. agalactiae (group B strep), E. coli, Klebsiella sp., Enterobacter
sp.
Elderly patients are more susceptible to sepsis, have less physiologic reserve
to tolerate the insult from infection, and are more likely to have underlying
diseases, all of which adversely impact survival. In addition, elderly patients
are more likely to have atypical or nonspecific presentations when septic.
Sepsis and septic shock in the immunocompromised patient is associated
with a wide variety of bacteria and fungi.
Gram-negative septic shock:
50% of total cases of sepsis.
Gram-positive septic shock:
more gram positive cases of septic shock are seen due to the increased
incidence in pneumonia and in the use of intravascular devices, 50% of cases
sepsis.
Factors contributing to the increasing incidence of sepsis:
1. aggressive oncological chemotherapy and radiation therapy
2. widespread us of corticosteroid and immunosuppressive therapies for
organ transplants and inflammatory diseases
3. longer lives of patients predisposed to sepsis, the elderly, diabetics,
cancer patients, patients with major organ failure, and with
granulocyopenia.
4. Neonates are more likely to develop sepsis (ex. group B Streptococcal
infections).
5. increased use of invasive devices such as surgical protheses,
inhalation equipment, and intravenous and urinary catheters.
6. indiscriminate use of antimicrobial drugs that create conditions of
overgrowth, colonization, and subsequent infection by aggressive,
antimicrobial-resistant organisms.
150
The infection site helps in determining the most likely cause of a patients
sepsis
Suspected Source of Sepsis

Lung Abdomen Skin/soft tissue Urinary tract CNS
Major Streptococcus Escherichiae Streptoccocus Escherichia Streptococcus
Community pneumoniae coli pyogenes coli pneumoniae
Acquired Hemophilus Bacteriodes Staphylococcus Klebsiella sp Neiserria
Pathogens influenzae fragilis aureus Enterobacter meningitides
Legionella sp. Clostridium sp sp Listeria
Chlamydiae Polymicrobial Proteus sp monocytogenes
pneumoniae infections Escherichia coli
Aerobic gram Heomophilus
negative bacilli influenzae
Pseudomonas
aeruginosa
Anaeorobes
Staphylococcus sp
Major Aerobic gram Aerobic gram Staphylococcus Aerobic gram Pseudomonas
Nosocomial negative bacilli negative aureus Aerobic negative bacilli aeruginosa
Pathogens bacilli gram negative bacilli Enterococcus Escherichia coli
Anaerobes sp Klebsiella sp
Candida sp Staphylococcus sp
Source: (usually an endogenous source of infection)

intestinal tract
oropharynx
instrumentation sites
contaminated inhalation therapy equipment
IV fluids.
Most frequent sites of infection: Lungs, abdomen, and urinary tract. Other
sources include the skin/soft tissue and the CNS. The source of the infection
is an important determinant of clinical outcome. Severe sepsis is most likely to
occur in patients with nosocomial pneumonia. Patients with intra-abdominal
infection and polymicrobial bacteremia or postoperative wound infections and
bacteremia are at significant risk for severe sepsis. Bacteremia associated
with intravascular catheters or indwelling urinary catheters carries a lower risk
of developing septic shock.
Patients at increased risks of developing sepsis:
Underlying diseases: neutropenia, solid tumors, leukemia, dysproteinemias,
cirrhosis of the liver, diabetes, AIDS, serious chronic conditions.
Surgery or instrumentation: catheters.
Prior drug therapy: Immuno-suppressive drugs, especially with broad-
spectrum antibiotics.
Age: males, above 40 y; females, 20-45 y.
151
Miscellaneous conditions: childbirth, septic abortion, trauma and widespread
burns, intestinal ulceration.
PATHOGENESIS
Microbial triggers of disease:
gram-negative bacteria= endotoxin, formyl peptides, exotoxins, and proteases
gram-positive bacteria= exotoxins, superantigens (toxic shock syndrome toxin
(TSST), streptococcal pyrogenic exotoxin A (SpeA)), enterotoxins,
hemolysins, peptidoglycans, and lipotechoic acid
fungal cell wall material.
Sequence of events: Sepsis can be simply defined as a spectrum of clinical
conditions caused by the immune response of a patient to infection that is
characterized by systemic inflammation and coagulation. It includes the full
range of response from systemic inflammatory response (SIRS) to organ
dysfunction to multiple organ failure and ultimately death.
This is a very complex sequence of events and much work still needs to be
done to completely understand how a patient goes from SIRS to septic shock.
Patients with septic shock have a biphasic immunological response. Initially
they manifest an overwhelming inflammatory response to the infection. This is
most likely due to the pro-inflammatory cytokines Tumor Necrosis Factor
(TNF), IL-1, IL-12, Interferon gamma (IFNgamma), and IL-6.
The body then regulates this response by producing anti-inflammatory
cytokines (IL-10), soluble inhibitors [TNF receptors, IL-1 receptor type II, and
IL-1RA (an inactive form of IL-1)]. Which is manifested in the patient by a
period of immunodepression. Persistence of this hyporesponsiveness is
associated with increased risk of nosocomial infection and death.
This systemic inflammatory cascade is initiated by various bacterial
products. These bacterial products (gram-negative bacteria= endotoxin,
formyl peptides, exotoxins, and proteases, gram-positive bacteria=
exotoxins, superantigens (toxic shock syndrome toxin (TSST), streptococcal
pyrogenic exotoxin A (SpeA)), enterotoxins, hemolysins, peptidoglycans, and
lipotechoic acid, and fungal cell wall material) bind to cell receptors on the
host's macrophages and activate regulatory proteins (Nuclear Factor Kappa
B). Endotoxin activates the regulatory proteins by interacting with several
receptors. The CD receptors pool the LPS-LPS binding protein complex on
the surface of the cell and then the TLR receptors translate the signal into the
cells.
The pro-inflammatory cytokines produced are tumor necrosis factor (TNF),

Interleukins 1, 6 and 12 and Interferon gamma (IFNgamma). These cytokines
can act directly to affect organ function or they may act indirectly through
secondary mediators. The secondary mediators include nitric oxide,
thromboxanes, leukotrienes, platelet-activating factor, prostaglandins, and
complement. TNF and IL-1 (as well as endotoxin) can also cause the release
of tissue-factor by endothelial cells leading to fibrin deposition and
disseminated intravascular coagulation (DIC).
Then these primary and secondary mediators cause the activation of the
coagulation cascade, the complement cascade and the production of
152
prostaglandins and leukotrienes. Clots lodge in the blood vessels which
lowers profusion of the organs and can lead to multiple organ system failure.
In time this activation of the coagulation cascade depletes the patient's ability
to make clot resulting in DIC and ARDS.
The cumulative effect of this cascade is an unbalanced state, with
inflammation dominant over antiinflammation and coagulation dominant over
fibrinolysis. Microvascular thrombosis, hypoperfusion, ischemia, and tissue
injury result. Severe sepsis, shock, and multiple organ dysfunction may occur,
leading to death.
Signs and Symptoms
Symptoms of sepsis are usually nonspecific and include fever, chills, and
constitutional symptoms of fatigue, malaise, anxiety, or confusion. These
symptoms are not pathognomonic for infection and may be seen in a wide
variety of noninfectious inflammatory conditions. They may be absent in
serious infections, especially in elderly individuals.
Definitions
Systemic Inflammatory Response Syndrome (SIRS): Patient presents with
two or more of the following criteria.
temperature > 38C or < 36C
heart rate > 90 beats/minute
respiration > 20/min or PaCO2 < 32mm Hg
leukocyte count > 12,000/mm3, < 4,000/mm3 or > 10% immature (band) cells
Sepsis: SIRS plus a documented infection site (documented by positive
culture for organisms from that site). Blood cultures do not need to be
positive. While SIRS, sepsis, and septic shock are associated commonly with
bacterial infection, bacteremia may not be present. Bacteremia is the
presence of viable bacterial within the liquid component of blood. Bacteremia
may be transient, as is seen commonly after injury to a mucosal surface,
primary (without an identifiable focus of infection), or more commonly
secondary, to an intravascular or extravascular focus of infection.
Severe Sepsis: Sepsis associated with organ dysfunction, hypoperfusion
abnormalities, OR hypotension. Hypoperfusion abnormalities include but are
not limited to:
lactic acidosis,
oliguria,
or an acute alteration in mental status.
Septic Shock: Sepsis-induced hypotension despite fluid resuscitation PLUS
hypoperfusion abnormalities.
Organ Dysfunctions associated with Severe Sepsis and Septic Shock:
Lungs: early fall in arterial PO2, Acute Respiratory Distress Syndrome
(ARDS): capillary-leakage into alveoli; tachypnea, hyperpnea
Kidneys (acute renal failure): oliguria, anuria, azotemia, proteinuria
Liver- elevated levels of serum bilirubin, alkaline phosphatase, cholestatic
jaundice
Digestive tract- nausea, vomiting, diarrhea and ileus
Skin ecthyma gangrenosum (think Pseudomonas aeruginosa in
neutropenic patients), Petechia or purpura (think Neisseria meningitidis or
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Rickettsia rickettsia (if evidence of tick bite)), Hemorrhage or bullous lesions in
patient who has eaten raw oysters (Vibrio vulnificus), generalized
erythroderma (Toxic Shock Syndrome= Staphylococcus aureus or
Streptococcus pyogenes)
Heart- cardiac output is initially normal or elevated,
Brain - confusion
Multiple Organ Dysfunction Syndrome (MODS): Presence of altered organ
function in an acutely ill patient such that homeostasis cannot be maintained
without intervention.
Complications:
Adult respiratory distress syndrome (ARDS)
Disseminated Intravascular Coagulation (DIC)
Acute Renal failure (ARF)
Intestinal bleeding
Liver failure
Central Nervous system dysfunction
Heart failure
Death
The reported incidence of these complications in SIRS and sepsis in different
studies is about 19% for CNS dysfunction, 2-8% for ARDS, 12% for liver
failure, and 8-18% for DIC.
In septic shock, ARDS has been observed in about 18%, DIC in about 38%,
and renal failure in about 50%.
Diagnosis
The diagnosis of sepsis requires a high index of suspicion, the taking of an
good history, physical examination, appropriate laboratory tests, and a close
follow-up of hemodynamic status.
History
Helps in determining if the infection was community or nosocomially acquired
and if the patient is immunocompromised. Important details include exposure
to animals, travel, tick bites, occupational hazards, alcohol use, seizures, loss
of consciousness, medications, and underlying diseases that may predispose
the patient to specific infectious agents. Some clues to a septic event include:
Fever or unexplained signs with malignancy or instrumentation
Hypotension Oliguria or anuria
Tachypnea or hyperpnea Hypothermia without obvious cause
Bleeding
Physical Examination
A thorough physical exam is essential. In all neutropenic patients and in
patients with as suspected pelvic infection the physical exam should include
rectal, pelvic, and genital examinations. Such exams may reveal rectal,
perirectal, and/or perineal abscesses, pelvic inflammatory disease and/or
abscesses, or prostatitis.
Laboratory data
Respiratory alkalosis signals impending shock that is reversible with fluid
resuscitation. Metabolic acidosis can develop just prior to hypotension or can
occur at the same time. Metabolic acidosis can signal the beginning of the
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end for the patient. Treatment should be instituted before metabolic acidosis
begins.
Other tests tests include full blood count with differential count, C-reactive
protein, urinalysis, coagulation profile, glucose, blood urea, nitrogen,
creatinine, electrolytes, liver function tests, lactic acid level, arterial blood gas,
electrocardiogram, and a chest X-ray. Cultures of blood, sputum, urine, and
other obviously infected sites should be performed. Gram's stain of normally
sterile sites (blood, CSF, articular fluid, pleural space) by aspiration. At least 2
sets (some believe 3) of blood cultures should be obtained over a 24hr period.
Sample volume: there is often less than 1 bacterium/ml in adults (higher in
children). Draw 10-20 ml per sampling in adults (1-5 ml in children) and
inoculate both trypticase soy broth and thioglycolate broth. Sample time: for
intermittent fever spikes, the bacteremia is most prominent 0.5 hr before the
spike. If antibiotic therapy has been initiated, some antibiotics can be
deactivated in the clinical lab.
Depending on the patient's clinical status and associated risks other studies
could include abdominal X-ray, CAT scans, MRI, 2D echocardiograms, and/or
lumbar puncture.
Other laboratory findings:
Early sepsis;
leukocytosis with left shift, thrombocytopenia, hyperbilirubinemia, and
proteinuria. Leukopenia may occur. Neutrophils may contain toxic
granulations, Dohle bodies, or cytoplasmic vacuoles. Hyperventilation
commonly induces respiratory alkalosis. Hypoxemia correctable with oxygen.
Diabetics can develop hyperglycemia. Serum lipids are elevated.
Late sepsis:
Thrombocytopenia worsens with prolongation of thrombin time, decreased
fibrinogen, and presence of D-dimers suggesting DIC. Azotemia, and
hyperbilirubinemia are more prominent. Aminotranferases (liver enzymes)
become elevated. When respiratory muscles fatigue the accumulation of
serum lactate occurs. Metabolic acidosis (increased anion gap) supervenes
the respiratory alkalosis. Hypoxemia not correctable even with 100% oxygen.
Diabetic hyperglycemia can precipitate ketoacidosis worsening the
hypotension.
Therapy
1. Immediate Stabilization of the Patient.
The immediate concern for patients with severe sepsis is reversal of life-
threatening abnormalities (ABCs: airway, breathing, circulation). Altered
mental status or depressed level of consciousness secondary to sepsis may
require immediate protection of the patient's airway. Intubation may also be
necessary to deliver higher oxygen concentrations. Mechanical ventilation
may help lower oxygen consumption by the respiratory muscles and increase
oxygen availibility for other tissues. Circulation may be compromised and
significant decreases in blood pressure may require aggressive combined
empiric therapy with fluids (with crystalloids or colloids) and
inotropes/vasopressors (dopamine, dobutamine, phenylephrine, epinephrine,
or norepinephrine). In severe sepsis monitoring of the circulation may be
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necessary. Normal CVP (central venous pressure) is 10-15 cm of 0.9% NaCl;
normal PAW (pulmonary arterial wedge pressure) is 14-18 mm Hg; maintain
adequate plasma volume with fluid infusion. Patients with severe sepsis
should be in ICU. Their vital signs (blood pressure, heart rate, respiratory rate,
and temperature) should be monitored. The frequency depending on how
severe the sepsis. Maintain adequate cardiac output and ventilation with
drugs. Consider dialysis to assist kidney function. Maintain arterial blood
pressure in hypotensive patients with vasoactive drugs, e.g., dopamine,
dobutamine, or norepinephrine.
2. The blood must be rapidly cleared of microorganisms.
Certain antimicrobial agents may cause the patients to get worse. It is
believed that certain antimicobials cause more LPS to be released cause
more problems for the patient. Antimicrobials that do NOT cause the patient to
get worse are: carbapenems, ceftriaxone, cefepime, glycopeptides,
aminoglycosides, and quinolones.
Prompt institution of empiric treatment with antimicrobials is essential. The
early institution of antimicrobials has been shown to decrease the
development of shock and to lower the mortality rate. After the appropriate
samples are obtained from the patient a regimen of antimicrobials with broad
spectrum of activity is needed. This is because antimicrobial therapy is almost
always instituted before the organisms causing the sepsis are identified. The
drugs used depends on the source of the sepsis*.
Community acquired pneumonia a 2 drug regimen is usually utilized. Usually
a third (ceftriaxone) or fourth (cefepime) generation cephalosporin is given
with an aminoglycoside (usually gentamicin).
Nosocomial pneumonia: Cefipime or Imipenem-cilastatin and an
aminoglycoside.
Abdominal infection: Imipenem-cilastatin or Pipercillin-tazobactam and
aminoglycoside.
Nosocomial abdominal infection: Imipenem-cilastatin and aminoglycoside or
Pipercillin-tazobactam and Amphotericin B.
Skin/soft tissue: Vancomycin and Imipenem-cilastatin or Piperacillin-
tazobactam
Nosocomial skin/soft tissue: Vancomycin and Cefipime
Urinary tract infection: Ciprofloxacin and aminoglycoside
Nosocomial urinary tract infection: Vancomycin and Cefipime
CNS infection: Vancomycin and third generation cephalosporin or Meropenem
Nosocomial CNS infection: Meropenem and Vancomycin
*Drugs will change with time. These drug choices are just to show you
different antimicrobial agents are chosen depending on the most likely cause
of the patient's sepsis.
Single drug regimens are usually only indicated when the organism causing
sepsis has been identified and antibiotic sensitivity testing has revealed which
antimicrobials the organism is sensitive to.
3. The original focus of infection must be treated.
Remove foreign bodies. Drain purulent exudate, particularly for anaerobic
infections. Remove infected organs; debride or amputate gangrenous tissues.
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New Drug in Treating Severe Sepsis:
Eli Lilly and Company announced in 2001 the results of a Phase III clinical
trial that demonstrated drotrecogin alfa (recombinant human activated protein
C, Xigris used to be called Zovant) could reduce the relative risk of death from
sepsis with associated acute organ dysfunction (known as severe sepsis) by
19.4 percent. These patients had Acute Physiology and Chronic Health
Evaluation II Scores (APACHE II) of 25-53. To treat with this protein the
patient should have an APACHE II score of between 25 and 53. Please note
that patients treated with this protein also are at an increased risk of bleeding.
This risk is highest during infusion of the protein.
It is the first agent approved by the FDA effective in the treatment of severe
sepsis proven to reduce mortality. Activated Protein C (Xigris) mediates many
actions of body homeostasis. It is a potent agent for the:
suppression of inflammation [a. directly suppresses monocyte production of
nuclear factor- -
proinflammatory, c. minimizes the expression of E-selectin on endothelial
walls, producing dose-dependent inhibition of leukocyte adhesion at the site of
infection. Reduced leukocyte/endothelial interaction down regulates oxygen
radical release, decreasing vascular damage.],
prevention of microvascular coagulation [a. proteolytic inactivation of Factors
Va and VIIIa preventing thrombin formation.]
reversal of impaired fibrinolysis [a. binds with plasminogen activator inhibitor-1
(PAI-1), causing inactivation of PAI-1. This in turn reduces the inhibition of
tissue plasminogen activator (t-PA), allowing t-PA to stimulate fibrinolysis.
Fibrin is broken down, and microcirculation is restored.].
Eli Lilly and Company announced in 2001 the results of a Phase III clinical
trial that demonstrated drotrecogin alfa (recombinant human activated protein
C, Xigris used to be called Zovant) could reduce the relative risk of death from
sepsis with associated acute organ dysfunction (known as severe sepsis) by
19.4 percent. These patients had Acute Physiology and Chronic Health
Evaluation II Scores (APACHE II) of 25-53. To treat with this protein the
patient should have an APACHE II score of between 25 and 53. Please note
that patients treated with this protein also are at an increased risk of bleeding.
This risk is highest during infusion of the protein.
It is the first agent approved by the FDA effective in the treatment of severe
sepsis proven to reduce mortality. Activated Protein C (Xigris) mediates many
actions of body homeostasis. It is a potent agent for the:
suppression of inflammation [a. directly suppresses monocyte production of
nuclear factor- -
proinflammatory, c. minimizes the expression of E-selectin on endothelial
walls, producing dose-dependent inhibition of leukocyte adhesion at the site of
infection. Reduced leukocyte/endothelial interaction down regulates oxygen
radical release, decreasing vascular damage.],
prevention of microvascular coagulation [a. proteolytic inactivation of Factors
Va and VIIIa preventing thrombin formation.]
reversal of impaired fibrinolysis [a. binds with plasminogen activator inhibitor-1
(PAI-1), causing inactivation of PAI-1. This in turn reduces the inhibition of
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tissue plasminogen activator (t-PA), allowing t-PA to stimulate fibrinolysis.
Fibrin is broken down, and microcirculation is restored.].
Prevention
Avoid trauma to mucosal surfaces that are normally colonized by Gram-
negative bacteria.
Use trimethoprim-sulfamethoxazole prophylactically in leukemic children.
Use topical silver nitrate, silver sulfadiazine, or sulfamylon prophylactically in
burn patients.
Apply polymyxin spray to the posterior pharynx to prevent nosocomial Gram-
negative pneumonia.
Sterilization of the bowel aerobic flora with polymyxin or gentamycin with
vancomycin and nystatin were effective in reducing Gram-negative sepsis in
neutropenic patients.
Protective environments for patients at risk have not been to successful
because most infections have endogenous origins.
To protect neonates from Group B strep sepsis obtain vaginal/rectal swab
samples at 35 to 37 weeks' gestation. Culture for Streptococcus agalactiae
(leading cause of neonatal sepsis). If positive for Group B strep then give the
mother intrapartum penicillin This will lower Group B strep infections by about
78%.
MULTIPLE ORGAN FAILURE

Circulatory failure
Criteria for diagnosis; Bradycardia (heart rate <50 bpm), Hypotension (mean
arterial pressure <50 mmHg), Ventricular tachycardia or fibrillation, Metabolic
acidosis (pH <7.2)
Management; Optimise cardiac preload, Maximise cardiac contractility with
inotropes, Maximise perfusion pressures with vasopressors, Correct anaemia,
Treat arrhythmia
Respiratory failure
Criteria for diagnosis; Respiratory rate <5 or >40 breaths per minute,
Hypercapnia (PaCO2 > 6.7 kPa), Hypoxaemia
Management; Oxygen, Mechanical ventilation, PEEP or CPAP, Extra or
intracorporeal gas exchange
Acute renal failure
Criteria for diagnosis; Urine output < 400 ml per 24 hours, Serum creatinine >
150 mmol/l
Management; Conservative measures, Fluid and potassium restriction, Drug
dose adjustment. Dialysis
Haematological failure
Criteria for diagnosis; Leucopenia (WCC < 1000 cell / mm3),
Thrombocytopenia (platelet < 20,000 / mm3), Evidence of disseminated
intravascular coagulation Management; Red cell and platelet transfusion,
Fresh frozen plasma, Correct antithrombin III deficiency
Hepatic failure
Criteria for diagnosis; Coagulation defect, Rising hepatic enzymes
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Management; Fresh frozen plasma, Nutritional support, Correct
hypoalbuminaemia
Gastrointestinal failure
Criteria for diagnosis; Ileus, Gastroparesis, Haemorrhage
Management; Parenteral nutrition, Stress ulcer prophylaxis, Selective
gastrointestinal decontamination.
Neurological failure
Criteria for diagnosis; Depressed level of consciousness (Glasgow coma
score <6), Fits
Management; Oxygenation, Control seizures
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)

Acute respiratory distress syndrome was first recognised in 1960s
Initially termed adult respiratory distress syndrome
Can occurs in both children and adults
Occurs following many different inflammatory insults to the lungs
Definition
Two condition recognised
Acute lung injury (ALI)
Acute respiratory distress syndrome (ARDS)
Both consist of an acute lung injury with:
Bilateral pulmonary infiltrates on chest x-ray
PCWP less than 18 mmHg
No evidence of left atrial hypertension
In ALI - PaO2 / FiO2 < 200
In ARDS - PaO2 / FiO2 < 300
Aetiology
Direct lung injury
Pneumonia
Aspiration pneumonitis
Pulmonary contusion
Fat embolism
Inhalational injury
Indirect lung injury
Sepsis
Trauma
Cardiopulmonary bypass
Acute pancreatitis
Pathology
Irrespective of aetiology the main pathological feature is diffuse alveolar
damage
Endothelial injury results in increased permeability
Protein-rich exudate found in alveoli
Neutrophils are important in inflammatory process
Cytokines and enzymes may be responsible for many of the features
Resolution of inflammation can occur
Usually associated with some degree of pulmonary fibrosis
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Clinical features
ARDS is usually a progressive clinical problem
Presents with acute respiratory failure
Hypoxaemia is often refractory to increasing respiratory support
Bilateral infiltrates present on chest x-ray
With time can progress to fibrosing alveolitis
Lung compliance is reduced and hypoxaemia persists
Pulmonary hypertension can progress to right heart failure
Resolution can occur over 6-12 months
Lung function can return to normal
Overall mortality is approximately 50%
Management
Supportive intensive care therapy is important
Sepsis should be treated with appropriate antibiotics
Careful fluid balance is important
Over hydration should be avoided
Nutritional status should be addressed
Mechanical ventilation is important but the exact strategy is controversial
Generally believed that ventilation with low tidal volumes is beneficial
High tidal volumes can exacerbate lung injury
Role of positive end-expiratory pressure unclear
Inhaled nitric oxide or surfactant are of no proven benefit
Steroids may have some beneficial effect
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CHAPTER 20
PRINCIPLES OF SURGICAL ONCOLOGY
MOLECULAR BASIS OF CANCER

Cellular Kinetics
Generation time is the time required for a quiescent cell to complete a cycle in
cell division and give rise to 2 daughter cells. Malignant cells usually have a
shorter generation time than nonmalignant cells from the same tissue, and
there usually are a smaller percentage of cells in G 0 (resting phase). Initial
exponential tumor growth is followed by a plateau phase when cell death
nearly equals the rate of formation of daughter cells. The slowing in growth
rate is likely related to exhaustion of the supply of nutrients and O 2 for the
rapidly expanding tumor. Small tumors have a greater percentage of actively
dividing cells than do large tumors.
Cellular kinetics of particular tumors is an important consideration in the
design of antineoplastic drug regimens and may influence the dosing
schedules and timing intervals of treatment. Many antineoplastic drugs are
effective only if cells are actively dividing, and some drugs work only during a
specific phase of the cycle and thus require prolonged administration to catch
dividing cells during the phase of maximal sensitivity.
Tumor Growth and Metastasis
As a tumor grows, nutrients are provided by direct diffusion from the
circulation. Local growth is facilitated by enzymes (eg, proteases) that destroy
adjacent tissues. As tumor volume increases, tumor angiogenesis factors are
produced to promote formation of the vascular supply required for further
tumor growth.
Fig 1
The cell cycle
G0 = resting phase (nonproliferation of cells); G 1 = variable pre-DNA synthetic

phase (12 h to a few days); S = DNA synthesis (usually 2 to 4 h); G2 = post-
DNA synthesis (2 to 4 h)a tetraploid quantity of DNA is found within cells;
M1 = mitosis (1 to 2 h).
Almost from inception, a tumor may shed cells into the circulation. From
animal models, it is estimated that a 1-cm tumor sheds > 1 million cells/24 h
into the venous circulation. Although most circulating tumor cells die as a
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result of intravascular trauma, an occasional cell may adhere to the vascular
endothelium and penetrate into surrounding tissues, generating independent
tumors (metastases) at distant sites. Metastatic tumors grow in much the
same manner as primary tumors and may subsequently give rise to other
metastases.
Experiments suggest that through random mutation, a subset of cells in the
primary tumor may acquire the ability to invade and migrate to distant sites,
resulting in metastasis.
Molecular Abnormalities
Genetic mutations are responsible for the generation of cancer cells. These
mutations alter the quantity or function of protein products that regulate cell
growth and division and DNA repair. Two major categories of mutated genes
are oncogenes and tumor suppressor genes.
Oncogenes: These are abnormal forms of normal genes (proto-oncogenes)
that regulate various aspects of cell growth. Mutation of these genes may
result in direct and continuous stimulation of the pathways (eg, intracellular
signal transduction pathways, transcription factors, secreted growth factors)
that control cellular growth and division, DNA repair, angiogenesis, and other
physiologic processes.
There are > 100 known oncogenes that may contribute to human neoplastic
transformation. For example, the ras gene encodes the Ras protein, which
regulates cell division. Mutations may result in the inappropriate activation of
the Ras protein, leading to uncontrolled cell growth and division. In fact, the
Ras protein is abnormal in about 25% of human cancers. Other oncogenes
have been implicated in specific cancers. These include
Her2/neu (breast cancer)
Bcr-abl(chronic myeloid leukaemia, B-cell acute lymphocytic leukaemia)
c-myc (Burkits lymphoma)
N-myc (small cell lung cancer, neuroblastoma)
Specific oncogenes may have important implications for diagnosis, therapy,
and prognosis.
Oncogenes typically result from acquired somatic cell mutations secondary to
point mutations (eg, from chemical carcinogens), gene amplification (eg, an
increase in the number of copies of a normal gene), or translocations.
Occasionally, mutation of genes results in inheritance of a cancer
predisposition, as in the inheritance of BR CA1 or BRCA2 in families with a
high incidence of breast or ovarian cancer.
Tumor suppressor genes:
Genes such as the p53 gene play a role in normal cell division and DNA
repair and are critical for detecting inappropriate growth signals in cells. If
these genes, as a result of inherited or acquired mutations, become unable to
function, genetic mutations in other genes can proceed unchecked, leading to
neoplastic transformation.
As with most genes, 2 alleles are present that encode for each tumor
suppressor gene. A defective copy of one gene may be inherited, leaving only
one functional allele for the individual tumor suppressor gene. If a mutation is
acquired in the other allele, the normal protective mechanisms of the tumor
162
suppressor gene are lost, and dysfunction of other protein products or DNA
damage may escape unregulated, leading to cancer. For example, the
retinoblastoma (RB) gene encodes for the protein Rb, which regulates the cell
cycle by stopping DNA replication. Mutations in the RB gene family occur in
many human cancers, allowing affected cells to divide continuously.
Another important regulatory protein, p53, prevents replication of damaged
DNA in normal cells and promotes cell death (apoptosis) in cells with
abnormal DNA. Inactive or altered p53 allows cells with abnormal DNA to
survive and divide. Mutations are passed to daughter cells, conferring a high
probability of neoplastic transformation. The p53 gene is defective in many
human cancers. As with oncogenes, mutation of tumor suppressor genes
such as p53 or RB in germ cell lines may result in vertical transmission and a
higher incidence of cancer in offspring.
Chromosomal abnormalities:
Gross chromosomal abnormalities can occur through deletion, translocation,
or duplication. If these alterations activate or inactivate genes that result in a
proliferative advantage over normal cells, then a tumor may develop.
Other influences:
Most cancers likely involve several of the mechanisms described above that
lead to neoplastic conversion.
Telomeres are nucleoprotein complexes that cap the ends of chromosomes
and maintain their integrity. In normal tissue, telomere shortening (with aging)
results in a finite limit in cell division. The enzyme telomerase provides for
telomere synthesis and maintenance; thus telomerase may potentially allow
for cellular immortality. Activation of telomerase in tumors allows continuous
proliferation of tumors.
Environmental Factors
Infections:
Viruses contribute to the pathogenesis of human cancers. Pathogenesis may
occur through the integration of viral genetic elements into the host DNA.
These new genes are expressed by the host; they may affect cell growth or
division or disrupt normal host genes required for control of cell growth and
division. Alternatively, viral infection may result in immune dysfunction,
leading to decreased immune surveillance for early tumors.
Cancer-Associated Viruses:
Epstein-Barr virus; Burkitt's lymphoma, Nasopharyngeal carcinoma
Hepatitis B or hepatitis C virus; Hepatocellular carcinoma
Herpesvirus 8; Kaposi's sarcoma
Human papillomaviruses; Anal carcinoma, Cervical carcinoma, Head and
neck carcinoma
Human T-lymphotrophic virus; T-cell lymphomas
Bacteria may also cause cancer. Helicobacter pylori infection increases the
risk of several kinds of cancer (gastric adenocarcinoma, gastric lymphoma,
mucosa-associated lymphoid tissue [MALT] lymphoma).
Parasites of some types can lead to cancer. Schistosoma haematobium
causes chronic inflammation and fibrosis of the bladder, which may lead to
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cancer. Opisthorchis sinensis has been linked to carcinoma of the pancreas
and bile ducts.
Radiation: Ultraviolet radiation may induce skin cancer (eg, basal and
squamous cell carcinoma, melanoma) by damaging DNA. This DNA damage
consists of formation of thymidine dimers, which may escape repair due to
inherent defects in DNA repair (eg, xeroderma pigmentosum) or through rare,
random events.
Ionizing radiation is also carcinogenic. For example, survivors of the atomic
bomb explosions in Hiroshima and Nagasaki have a higher-than-expected
incidence of leukemia and other cancers. Similarly, the previous use of x-rays
to treat nonmalignant disease (acne, thymic or adenoid enlargement, and
ankylosing spondylitis) resulted in higher rates of acute and chronic
leukemias, Hodgkin and non-Hodgkin lymphomas, multiple myeloma, aplastic
anemia terminating in acute nonlymphocytic leukemia, myelofibrosis,
melanoma, and thyroid cancer. Use of x-rays in diagnostic imaging studies is
thought to increase risk of cancer. Industrial exposure (eg, to uranium by mine
workers) is linked to development of lung cancer after a 15- to 20-yr latency.
Long-term exposure to occupational irradiation or to internally deposited
thorium dioxide predisposes people to angiosarcomas and acute
nonlymphocytic leukemia.
Exposure to the radioactive gas radon, which is released from soil, increases
the risk of lung cancer. Normally, radon disperses rapidly into the atmosphere
and produces no harm. However, when a building is placed on soil with high
radon content, radon can accumulate within the building, sometimes
producing sufficiently high levels in the air to cause harm. In exposed people
who also smoke, the risk of lung cancer is further increased.
Common chemical carcinogens:
Environmental and industrial; aromatic amines (bladder cancer), arsenic (lung
cancer, skin cancer), Asbestos ( lung cancer, mesothelioma), Benzene
(leukaemia), chromates (lung cancer), diesel exhaust ( lung cancer),
formaldehyde (nasal cancer, nasophryngeal cancer), hair dyes (bladder
cancer), ionising radiation (leukaemia), manufactured mineral fibers (lung
cancer), nickel ( lung cancer, nasal sinus cancer), painting materials (lung
cancer), pesticides nonarsenic ( lung cancer), radon (lung cancer), radiation
therapy (leukaemia), ultraviolet radiation (skin cancer), vinyl chloride (hepatic
angiosarcoma), betel nuts (oropharyngeal cancer), tobacco ( bladder cancer,
cervical cancer, oesophageal cancer, head and neck cancer, kidney cancer,
lung cancer, pancreatic cancer, stomach cancer), alkylating drugs (
leukaemia), diethylstilbestrol ( cervicovaginal cancer in women exposed in
utero), oxymetholone (liver cancer), healthcare workers exposed to
antineoplastic drugs (adverse effects on reproduction)
Drugs and chemicals:
Estrogens in oral contraceptives may slightly increase the risk of breast
cancer, but this risk decreases over time. Estrogen and progestin used for
hormone replacement therapy also increase the risk of breast cancer.
Diethylstilbestrol (DES) increases the risk of breast cancer in women who
took the drug and increases the risk of vaginal carcinoma in daughters of
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these women who were exposed before birth. Long-term use of anabolic
steroids may increase the risk of liver cancer. Treatment of cancer with
chemotherapy drugs and with radiation therapy increases the risk of
developing a second cancer.
Chemical carcinogens can induce gene mutations and result in uncontrolled
growth and tumor formation (see Table 3 ) Other substances, called co-
carcinogens, have little or no inherent carcinogenic potency but enhance the
carcinogenic effect of another agent when exposed simultaneously.
Dietary substances: Certain substances consumed in the diet can increase
the risk of cancer. For instance, a diet high in fat has been linked to an
increased risk of colon, breast, and possibly prostate cancer. People who
drink large amounts of alcohol are at much higher risk of developing
esophageal cancer. A diet high in smoked and pickled foods or in barbecued
meats increases the risk of developing stomach cancer. People who are
overweight or obese have a higher risk of cancer of the breast, endometrium,
colon, kidneys, and esophagus.
Physical factors:
Chronic skin irritation leads to chronic dermatitis and, in rare cases, to
squamous cell carcinoma. This occurrence is presumably due to random
mutations that occur more frequently because of the increased cell turnover.
Immunologic Disorders
Immune system dysfunction as a result of inherited genetic mutation, acquired
disorders, aging, or immunosuppressants interferes with normal immune
surveillance of early tumors and results in higher rates of cancer. Known
cancer-associated immune disorders include
Ataxia-telangiectasia (acute lymphocytic leukemia [ALL], brain tumors, gastric
cancer)
Wiskott-Aldrich syndrome (lymphoma, ALL)
X-linked agammaglobulinemia (lymphoma, ALL)
Immune deficiency secondary to immunosuppressants or HIV infection (large
cell lymphoma, Kaposi's sarcoma)
Rheumatologic conditions, such as SLE, RA, and Sjgren's syndrome (B-type
lymphoma)
General immune disorders (lymphoreticular neoplasia)
CHILDHOOD CANCER, GENETICS

Introduction
An important development in cancer research over the past 2 decades has
been the recognition that genetic changes drive the pathogenesis of tumors of
both adulthood and childhood. These changes can be inherited and are,
therefore, found in every cell, but more often, they are somatically acquired
and restricted to tumor cells. In addition, these alterations affect 3 principal
categories of genes, as follows: proto-oncogenes, tumor suppressor genes,
and DNA repair genes. This article briefly discusses tumor suppressor genes
and then focuses on the role of proto-oncogenes in childhood cancer.
Tumor Suppressor Genes
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Inactivation of tumor suppressor genes, whose products normally provide
negative control of cell proliferation, contributes to malignant transformation in
various cell types. Knudson first proposed that two hits, or mutations, are
required for the development of retinoblastoma. His prediction was
subsequently supported by the cloning of the retinoblastoma tumor
suppressor gene (RB1) and by functional studies of the retinoblastoma
protein, Rb. The first mutation of RB1 in cases of retinoblastoma can be either
constitutional or somatic, whereas the second mutation is always somatic. In
the inherited form of retinoblastoma, the first mutation is present in the
germline; an early onset and a high frequency of bilateral disease
characterize these cases. In contrast, both mutations in nonhereditary
retinoblastoma are somatic.
Like Rb protein, many of the proteins encoded by tumor suppressor genes act
at specific points in the cell cycle. For example, the TP53 gene, located on
chromosome 17, encodes a 53-kd nuclear protein that functions as a cell
cycle checkpoint. As a transcription factor whose expression is increased by
DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to
allow DNA repair. The TP53 gene is also capable of stimulating apoptosis of
cells containing damaged DNA. Targeted disruption of TP53 in the mouse
leads to the development of various tumors. Germline mutation of one TP53
allele is found in patients with Li-Fraumeni syndrome who generally inherit a
mutated TP53 gene from an affected parent. Patients with Li-Fraumeni
syndrome are predisposed to sarcomas, breast cancer, brain tumors,
adrenocortical cell carcinoma, and acute leukemia; they have a 50%
probability of cancer development by age 30 years.
Another important class of tumor suppressor genes involved in cell cycle
control and in the generation of human cancers is the cyclin-dependent kinase
(CDK) inhibitors. These proteins negatively regulate the cell cycle by inhibiting
CDK phosphorylation of Rb protein and include p15INK4B, p16INK4A,
p18INK4C, p19INK4D, p19ARF, p21CIP1, p27KIP1, and p57KIP2. Although
carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes
appear to be limited, INK4A is among the most commonly mutated genes in
human tumors. The p16INK4A protein is a cell-cycle inhibitor that acts by
inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in
the control of the cell cycle by phosphorylating Rb protein.
Direct evidence linking the INK4A locus to tumorigenesis was provided by the
targeted disruption of exon 2 of INK4A in mice. Tumors that developed in
mice deficient in INK4A were enhanced by the topical application of
carcinogens and ultraviolet light. This locus, however, also encodes a protein
from an alternative reading frame, designated p19ARF. Interpretation of
INK4A knockout experiments was uncertain because targeted disruption of
exon 2 of INK4A also disrupts ARF. Further genetic analysis showed that
selective disruption of ARF reproduces the phenotype described for INK4A-
null mice; this finding indicates that ARF is a true tumor suppressor gene.
In addition, p19ARF binds to and promotes the degradation of MDM2, the
product of the murine double minute 2 gene, and this degradation leads to
accumulation of TP53 and to cell cycle arrest. Therefore, both INK4A and
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ARF appear to be tumor suppressor genes, acting through either the Rb
protein (INK4A) pathway or the TP53 (ARF) pathway in different tumor
subsets.
Although many other tumor suppressor genes are involved in human cancers,
the functions of their encoded proteins are not completely understood.
Similarly, the reason that germline mutations in tumor suppressor genes
predispose only to specific tumors is unclear. The characterization of
additional tumor suppressor genes and a better understanding of how their
inactivation leads to tumorigenesis should ultimately lead to improvements in
the treatment of childhood cancer.
Proto-oncogene Activation
Activation of proto-oncogenes is a common theme in childhood leukemias and
solid tumors. Transcription factors (proteins that bind to the regulatory
sequences of target genes) compose the largest class of oncogenes identified
in pediatric tumors. Oncogenic transcription factors commonly show close
homology to proteins with important regulatory functions in primitive
organisms; this homology indicates that the biochemical pathways leading to
cell transformation are well conserved in nature.
Tumor-specific translocations can oncogenically activate transcription factors
by at least 2 mechanisms. In B-progenitor acute lymphoblastic leukemia
(ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and
certain solid tumors, translocations fuse discrete portions of 2 different genes
to create chimeric transcription factors with oncogenic properties. Gene fusion
is also the mechanism by which tyrosine kinases become activated in ALL.
Alternatively, in T-cell and B-cell acute leukemia, transcription factor genes
are dysregulated by their juxtaposition with transcriptionally active T-cell
receptor (TCR) or immunoglobulin (IG) genes.
Genetics of Childhood Solid Tumors
Effective clinical management of rhabdomyosarcomas, the family of tumors
that includes Ewing sarcoma and primitive neuroectodermal tumor (PNET),
and neuroblastomas depends on unequivocal diagnosis that can guide the
selection of specific therapy. However, each of these tumors may first be seen
as a soft-tissue mass with the appearance of undifferentiated small round
cells. Although immunohistochemical analysis can help in the diagnostic
workup for these tumors, this method has limitations. Recently, molecular
diagnostic techniques have had an important role in ensuring diagnostic
accuracy. The identification of molecular alterations has important prognostic
and therapeutic implications.
Brain tumors
Various tumor suppressor genes are implicated in the development of
childhood brain tumors, including TP53 in brainstem gliomas and the PTEN
gene in glioblastoma multiforme. However, the best-studied tumor is
medulloblastoma, which is a PNET that arises in the cerebellum and is the
most common brain tumor in children. Loss of chromosome 17p is the most
common genetic abnormality in patients with medulloblastoma, occurring in as
many as 50% of cases. Although most tumors arise sporadically,
medulloblastoma also occurs in patients with Turcot syndrome (APC gene)
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and in those with Gorlin syndrome. The latter is characterized by
developmental anomalies, radiation sensitivity, basal cell carcinoma, a
propensity to develop medulloblastoma, and germline mutations in the PTC
gene that produce a protein capable of binding the hedgehog family of
signaling proteins. TRK-C is associated with a good prognosis and promotes
apoptosis. Epidermal growth factor receptor-2 (ERBB-2), PDGF receptor,
and insulin-like growth factor receptor are all associated with a poor
prognosis.
The following are suggested prognostic indicators of glioblastomas and other
gliomatous subtypes: p53 mutation and expression, overexpression or
amplification of EGFR, CDKN2A alterations and deletion, and MDM2
amplifications. MDM2 is the key to maintaining proliferation and apoptosis.
LOH of 10q leads to a shorter survival in glioblastoma multiforme and LOH of
1p and 19q may afford more favorable prognosis.
Basal cell carcinomas from patients with Gorlin syndrome often demonstrate
loss of the second PTC allele, suggesting that PTC functions as a tumor
suppressor gene. In addition, one allele of PTC is occasionally mutated in
sporadic medulloblastomas, implicating the PTC pathway in tumorigenesis.
Ependymomas are tumors composed of neoplastic ependymal cells that arise
from the walls of the cerebral ventricles or the spinal canal. Cytogenetic
studies suggest that ependymomas may represent a diverse group of tumors.
Genetic abnormalities found in childhood ependymomas include loss of
chromosome 22, alterations in chromosome 6, monosomy 13, and loss of
heterozygosity of 17p.
CLINICAL SEQUELAE OF CANCER

Cancer may lead to pain, weight loss, neuropathy, nausea, fatigue, seizures,
or obstruction of visceral organs. Death typically occurs as a result of failure of
one or more organ systems.
Pain in patients with metastatic cancer frequently results from bone
metastases, nerve or plexus involvement, or pressure exerted by a tumor
mass or effusion. Aggressive pain management is essential in the treatment
of cancer and for maintenance of quality of life.
Pleural effusions should be drained if symptomatic and monitored for
reaccumulation. If the effusion reaccumulates rapidly, thoracostomy tube
drainage and sclerosing agents or repeated catheter drainage should be
considered. Palliative surgical pleurectomy can be used for refractory
effusions in advanced malignant disease.
Spinal cord compression can result from cancer spread to the vertebrae and
requires immediate surgery or radiation therapy. Symptoms may include back
pain, lower extremity paresthesias, and bowel and bladder dysfunction.
Diagnosis is confirmed by CT or MRI.
Cancer patients often have complications due to clots in the veins of the lower
extremities. Tumors produce procoagulants, such as tissue factors, leading to
excess clot formation, particularly in after surgery. Anticoagulants may be
necessary to prevent pulmonary emboli.
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Metabolic and immune consequences of cancer can include hypercalcemia,
hyperuricemia, increased ACTH production, antibodies that produce
neurologic dysfunction, hemolytic anemia, and many other complications.
A diagnosis of cancer may be suspected based on history and physical
examination but requires confirmation by tumor biopsy and histopathologic
examination.
A complete history and physical examination may reveal unexpected clues to
early cancer.
History
Physicians must be aware of predisposing factors and must specifically ask
about familial cancer, environmental exposure (including smoking history),
and prior or present illnesses (eg, autoimmune disorders, previous
immunosuppressive therapy, hepatitis B or hepatitis C, HIV infection,
abnormal Papanicolaou test, human papillomavirus infection). Symptoms
suggesting occult cancer can include
Fatigue
Weight loss
Fevers
Night sweats
Cough
Hemoptysis
Hematemesis
Hematochezia
Change in bowel habits
Persistent pain
Physical examination
Particular attention should be paid to skin, lymph nodes, lungs, breasts,
abdomen, and testes. Prostate, rectal, and vaginal examinations are also
important. Findings help direct further testing, including x-rays and biopsies.
Testing
Tests include imaging tests, serum tumor markers, and biopsy.
Imaging tests often include plain x-rays, ultrasonography, CT, and MRI. These
tests assist in identifying abnormalities, determining qualities of a mass (solid
or cystic), providing dimensions, and establishing relationship to surrounding
structures, which may be important if surgery or biopsy is being considered.
Serum tumor markers may offer corroborating evidence in patients with
findings suggestive of a specific cancer .With some exceptions (eg, prostate-
specific antigen [PSA]), these markers do not have enough sensitivity and
specificity to be used for screening. They are the most useful in detecting
early relapse and monitoring response to therapy. Useful examples include
-Fetoprotein (hepatocellular carcinoma, testicular carcinoma)
Carcinoembryonic antigen (colon cancer)
-human chorionic gonadotropin (choriocarcinoma, testicular carcinoma)
Serum immunoglobulins (multiple myeloma)
DNA probes (eg, bcr probe to identify a chromosome 22 alteration in chronic
myelogenous leukemia)
CA 125 (ovarian cancer)
169
CA 27-29 (breast cancer)
PSA (prostate cancer)
Biopsy to confirm the diagnosis and tissue of origin is almost always required
when cancer is suspected or detected. The choice of biopsy site is usually
determined by ease of access and degree of invasiveness. If
lymphadenopathy is present, fine-needle or core biopsy may yield the tumor
type; if nondiagnostic, open biopsy is done. Other biopsy routes include
bronchoscopy for easily accessible mediastinal or central pulmonary tumors,
percutaneous liver biopsy if liver lesions are present, and CT- or ultrasound-
guided biopsy. If these procedures are not suitable, open biopsy may be
necessary.
Grading is a histologic measure of tumor aggressiveness and provides
important prognostic information. It is determined by examining the biopsy
specimen. Grade is based on the morphologic appearance of tumor cells,
including the appearance of the nuclei, cytoplasm, and nucleoli; frequency of
mitoses; and amount of necrosis. For many cancers, grading scales have
been developed
Molecular tests such as chromosomal analogues, fluorescent in situ
hybridization (FISH), PCR, and cell surface antigens (eg, in lymphomas,
leukemias) delineate the origin of metastatic cancers originating from an
unknown primary cancer or assist in recognizing chemotherapy resistance
(eg, in acute myelogenous leukemia).
Staging
Once a histologic diagnosis is made, staging (ie, determination of the extent
of disease) helps determine treatment decisions and prognosis. Clinical
staging uses data from the history, physical examination, imaging tests,
laboratory tests, and biopsy of bone marrow, lymph nodes, or other sites of
suspected disease. For staging of specific neoplasms, see details in the
organ-relevant chapter.
Imaging tests: Imaging tests, especially CT and MRI, can detect metastases
to brain, lung, or abdominal viscera, including the adrenal glands,
retroperitoneal lymph nodes, liver, and spleen. MRI (with gadolinium contrast)
is the procedure of choice for recognition and evaluation of brain tumors, both
primary and metastatic. PET scanning is increasingly being used to determine
the metabolic activity of a suspect lymph node or mass. Integrated PETCT
can be valuable, especially in lung, head and neck, and breast cancer and in
lymphoma.
Ultrasonography can be used to study orbital, thyroid, cardiac, pericardial,
hepatic, pancreatic, renal, and retroperitoneal areas. It may guide
percutaneous biopsies and differentiate renal cell carcinoma from a benign
renal cyst.
Nuclear scans can identify several types of metastases. Bone scans identify
abnormal bone growth (ie, osteoblastic activity) before it is visible on plain x-
ray. Thus, this technique is useless in neoplasms that are purely lytic (eg,
multiple myeloma); routine bone x-rays are the study of choice in such
diseases.
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Laboratory tests: Serum chemistries and enzymes may help staging. Elevated
liver enzyme (alkaline phosphatase, LDH, ALT) levels suggest the presence
of liver metastases. Elevated alkaline phosphatase and serum Ca may be the
first evidence of bone metastases. Elevated BUN or creatinine levels may
indicate an obstructive uropathy secondary to a pelvic mass, intrarenal
obstruction from tubular precipitation of myeloma protein, or uric acid
nephropathy from lymphoma or other cancers. Elevated uric acid levels often
occur in myeloproliferative and lymphoproliferative disorders.
Invasive tests: Mediastinoscopy is especially valuable in the staging of non
small cell lung cancer. When mediastinal lymph node involvement is found,
patients do not usually benefit from thoracotomy and lung resection but may
benefitt from chemoradiation and subsequent tumor resection.
Bone marrow aspiration and biopsy are especially useful in detecting
metastases from malignant lymphoma and small cell lung cancer, and their
role in breast and prostate cancer staging is expanding. Marrow biopsy is
positive at diagnosis in 50 to 70% of patients with malignant lymphoma (low
and intermediate grade) and in 15 to 18% of patients with small cell lung
cancer. Bone marrow biopsy should be done in patients with hematologic
abnormalities (ie, anemia, thrombocytopenia, pancytopenia) that cannot be
explained by other mechanisms.
Biopsy of regional lymph nodes is part of the evaluation of most tumors, such
as breast, lung, or colon cancers.
CANCER SCREENING
Cancer can sometimes be detected in asymptomatic patients via regular
physical examinations and screening tests.
Physical examinations for cancers of the thyroid, oral cavity, skin, lymph
nodes, testes, prostate, and ovaries should also be done during routine
medical care.
Screening tests are done in asymptomatic patients at risk. The rationale is
that early diagnosis may decrease cancer mortality by detecting cancer at an
early and curable stage. Early detection may allow for less radical therapy,
and reduce costs. Risks, however, include false-positive results, which
necessitate confirmatory tests (eg, biopsy, endoscopy) that can lead to
anxiety, significant morbidity, and significant costs; and false-negative results,
which may give a mistaken sense of security, causing patients to ignore
subsequent symptoms.
Screening for cancer should be done in the following circumstances:
When distinct high-risk groups can be identified (eg, people with certain
infections, exposures, or behaviors)
When the disorder has an asymptomatic period during which treatment would
alter outcome
When the morbidity of the disorder is significant
When an intervention is available that is acceptable and effective at changing
the natural history of the condition
The screening tests themselves should satisfy the following criteria:
Cost and convenience are reasonable.
Results are reliable and reproducible.
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Sensitivity and specificity are adequate.
The positive predictive value (probability that a person with a positive test
result has or will develop a disorder or condition is high in the population
screened, and few false-negative results occur.
The test or procedure is acceptable to patients.
Recommended screening schedules are constantly evolving based on
ongoing studies Overview of Cancer: Screening procedures in average-risk
asymptomatic people as recommended by the American Cancer Society.
Examinations for cancers of the thyroid, oral cavity, skin, lymph nodes, testes,
and ovaries should be done during routine medical examination
METASTATIC CARCINOMA OF UNKNOWN PRIMARY ORIGIN

A patient is considered to have carcinoma of unknown primary origin when a
tumor is detected at one or more metastatic sites and routine evaluation fails
to identify a primary tumor. Metastatic carcinoma of unknown primary origin
constitutes up to 7% of all cancers and poses a therapeutic dilemma, because
cancer treatment is typically directed at the specific primary tissue type.
The most common causative primary tumors are of the testis, lung, colon and
rectum, and pancreas. Examination of these areas should be thorough.
Types of testing used to help specify the primary site include
Laboratory testing
Imaging tests
Immunocytochemical and immunoperoxidase staining
Tissue analysis
Laboratory tests should include a CBC, urinalysis, stool examination for occult
blood, and serum chemistries (including prostate-specific antigen assays in
males).
Imaging should be limited to a chest x-ray, abdominal CT, and
mammography. An upper GI series and barium enema should be done if
blood is present in the stool.
On available cancerous tissue, a growing panel of immunocytochemical stains
has begun to help determine the primary tissue site. In addition,
immunoperoxidase staining for immunoglobulin, gene rearrangement studies,
and electron microscopy help diagnose large cell lymphoma, whereas
immunoperoxidase staining for -fetoprotein or -human chorionic
gonadotrophin may suggest germ cell tumors. Tissue analysis for estrogen
and progesterone receptors helps identify breast cancer, and
immunoperoxidase staining for prostate-specific antigen helps identify
prostate cancer.
Even if a precise histologic diagnosis cannot be made, one constellation of
findings may suggest an origin. Poorly differentiated carcinomas near or at
midline regions of the mediastinum or retroperitoneum in young or middle-
aged males should be considered germ cell neoplasmseven in the absence
of a testicular mass. Patients with this type of carcinoma should be treated
with a cisplatin. For most other unknown primary cancers, the responses to
this regimen and to other multidrug chemotherapy programs are modest and
of brief duration (eg, median survival < 1 yr)
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PARANEOPLASTIC SYNDROMES
Paraneoplastic syndromes are symptoms that occur at sites distant from a
tumor or its metastasis.
Although the pathogenesis remains unclear, these symptoms may be
secondary to substances secreted by the tumor or may be a result of
antibodies directed against tumors that cross-react with other tissue.
Symptoms may occur in any organ or physiologic system. Up to 20% of
cancer patients experience paraneoplastic syndromes, but often these
syndromes are unrecognized.
The most common cancers associated with paraneoplastic syndromes include
Lung carcinoma (most common)
Renal carcinoma
Hepatocellular carcinoma
Leukemias
Lymphomas
Breast tumors
Ovarian tumors
Neural cancers
Gastric cancers
Pancreatic cancers
Successful treatment is best obtained by controlling the underlying cancer, but
some symptoms can be palliated with specific drugs (eg, cyproheptadine for
carcinoid syndrome, bisphosphonates and corticosteroids for hypercalcemia).
General paraneoplastic symptoms: Patients with cancer often experience
fever, night sweats, anorexia, and cachexia. These symptoms may arise from
release of cytokines involved in the inflammatory or immune response or from
mediators involved in tumor cell death, such as tumor necrosis factor-.
Alterations in liver function and steroidogenesis may also contribute.
Cutaneous paraneoplastic syndromes: Patients may experience many skin
symptoms.
Itching is the most common cutaneous symptom experienced by patients with
cancer (eg, leukemia, lymphomas) and may result from hypereosinophilia.
Flushing may also occur and is likely related to tumor-generated circulating
vasoactive substances (eg, prostaglandins).
Pigmented skin lesions, or keratoses, may appear, including acanthosis
nigricans (GI cancer), generalized dermic melanosis (lymphoma, melanoma,
hepatocellular carcinoma), Bowen's disease (lung, GI, GU cancer), and large
multiple seborrheic keratoses, ie, Leser-Trlat signs (lymphoma, GI cancer).
Secretion of melanin precursors from tumors may promote formation of these
lesions.
Ichthyosis, or desquamation of the extensor surface of the extremities, may
also occur.
Hypertrichosis may manifest as sudden appearance of coarse hair on the face
and ears that resolves after resection or treatment of the tumor. Alternatively,
alopecia may occur with certain tumor types. The mechanism by which
alopecia occurs is not clear.
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Necrotizing migrating erythema may occur with glucagonomas.
Subcutaneous adipose nodular necrosis may result from release of proteolytic
enzymes from various pancreatic tumors.
Herpes zoster may result from reactivation of latent virus in patients with
immune system depression or dysfunction.
Endocrine paraneoplastic syndromes: The endocrine system is often affected
by paraneoplastic syndromes.
Cushing's syndrome (cortisol excess, leading to hyperglycemia, hypokalemia,
hypertension, central obesity, moon facies) may result from ectopic production
of ACTH or ACTH-like molecules, most often with small cell cancer of the
lung.
Abnormalities in water and electrolyte balance, including hyponatremia, may
result from production of ADH and parathyroid hormonelike hormones from
small cell and nonsmall cell lung cancer.
Hypoglycemia may result from production of insulin-like growth factors or
insulin production by pancreatic islet cell tumors or hemangiopericytomas.
Hypertension may result from abnormal epinephrine and norepinephrine
secretion (pheochromocytomas) or from cortisol excess (ACTH-secreting
tumors).
Other ectopically produced hormones include parathyroid hormone-related
peptide (PTHRPfrom squamous cell lung cancer, head and neck cancer,
bladder cancer), calcitonin (from breast cancer, small cell lung cancer, and
medullary thyroid carcinoma), and thyroid-stimulating hormone (from
gestational choriocarcinoma). PTHRP causes hypercalcemia and its
associated symptoms (polyuria, dehydration, constipation, muscle weakness);
calcitonin causes a fall in serum calcium, with contractions and cardiac
arrhythmias.
GI paraneoplastic syndromes: Watery diarrhea with subsequent dehydration
and electrolyte imbalances may result from tumor-related secretion of
prostaglandins or vasoactive intestinal peptide. Implicated tumors include
pancreatic islet cell tumors and others. Protein-losing enteropathies may
result from tumor mass inflammation, particularly with lymphomas.
Hematologic paraneoplastic syndromes: Patients with cancer may develop
pure RBC aplasia, anemia of chronic disease, leukocytosis (leukemoid
reaction), thrombocytosis, eosinophilia, basophilia, and disseminated
intravascular coagulation. In addition, idiopathic thrombocytopenic purpura
and a Coombs'-positive hemolytic anemia can complicate the course of
lymphoid cancers and Hodgkin lymphoma. Erythrocytosis may occur in
various cancers, especially renal cancers and hepatomas, due to ectopic
production of erythropoietin or erythropoietin-like substances, and monoclonal
gammopathies may sometimes be present.
Demonstrated mechanisms of hematologic abnormalities include tumor-
generated substances that mimic or block normal endocrine signals for
hematologic line development and generation of antibodies that cross-react
with receptors or cell lines.
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Neurologic paraneoplastic syndromes: Several types of peripheral neuropathy
are among the neurologic paraneoplastic syndromes. Cerebellar syndromes
and other central neurologic paraneoplastic syndromes also occur.
Peripheral neuropathy is the most common neurologic paraneoplastic
syndrome. It is usually a distal sensorimotor polyneuropathy that produces
mild motor weakness, sensory loss, and absent distal reflexes. The syndrome
is indistinguishable from that accompanying many chronic illnesses.
Subacute sensory neuropathy is a more specific but rare peripheral
neuropathy. Dorsal root ganglia degeneration and progressive sensory loss
with ataxia but little motor weakness develop; the disorder may be disabling.
Anti-Hu, an autoantibody, is found in the serum of some patients with lung
cancer. There is no treatment.
Guillain-Barr syndrome, another peripheral neuropathy, is more common in
patients with Hodgkin lymphoma than in the general population.
The Eaton-Lambert syndrome is an immune-mediated, myasthenia-like
syndrome with weakness usually affecting the limbs and sparing ocular and
bulbar muscles. It is presynaptic, resulting from impaired release of
acetylcholine from nerve terminals. An IgG antibody is involved. The
syndrome can precede, occur with, or develop after the diagnosis of cancer. It
occurs most commonly in men with intrathoracic tumors (70% have small or
oat cell lung carcinoma). Symptoms and signs include fatigability, weakness,
pain in proximal limb muscles, peripheral paresthesias, dry mouth, erectile
dysfunction, and ptosis. Deep tendon reflexes are reduced or lost. The
diagnosis is confirmed by finding an incremental response to repetitive nerve
stimulation: Amplitude of the compound muscle action potential increases >
200% at rates > 10 Hz. Treatment is first directed at the underlying
malignancy and sometimes induces remission. Guanidine (initially 125 mg po
qid, gradually increased to a maximum of 35 mg/kg), which facilitates
acetylcholine release, often lessens symptoms but may depress bone marrow
and liver function. Corticosteroids and plasmapheresis benefit some patients.
Subacute cerebellar degeneration causes progressive bilateral leg and arm
ataxia, dysarthria, and sometimes vertigo and diplopia. Neurologic signs may
include dementia with or without brain stem signs, ophthalmoplegia,
nystagmus, and extensor plantar signs, with prominent dysarthria and arm
involvement. The disease usually progresses over weeks to months, often
causing profound disability. Cerebellar degeneration may precede the
discovery of the cancer by weeks to years. Anti-Yo, a circulating autoantibody,
is found in the serum or CSF of some patients, especially women with breast
or ovarian cancer. MRI or CT may show cerebellar atrophy, especially late in
the disease. Characteristic pathologic changes include widespread loss of
Purkinje cells and lymphocytic cuffing of deep blood vessels. CSF
occasionally has mild lymphocytic pleocytosis. Treatment is nonspecific, but
some improvement may follow successful cancer therapy.
Opsoclonus (spontaneous chaotic eye movements) is a rare cerebellar
syndrome that may accompany childhood neuroblastoma. It is associated with
cerebellar ataxia and myoclonus of the trunk and extremities. Anti-Ri, a
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circulating autoantibody, may be present. The syndrome often responds to
corticosteroids and treatment of the cancer.
Subacute motor neuronopathy is a rare disorder causing painless lower motor
neuron weakness of upper and lower extremities, usually in patients with
Hodgkin lymphoma or other lymphomas. Anterior horn cells degenerate.
Spontaneous improvement usually occurs.
Subacute necrotizing myelopathy is a rare syndrome in which rapid ascending
sensory and motor loss occurs in gray and white matter of the spinal cord,
leading to paraplegia. MRI helps rule out epidural compression from
metastatic tumora much more common cause of rapidly progressive spinal
cord dysfunction in patients with cancer. MRI may show necrosis in the spinal
cord.
Encephalitis may occur as a paraneoplastic syndrome, taking several different
forms, depending on the area of the brain involved. Global encephalitis has
been proposed to explain the encephalopathy that occurs most commonly in
small cell lung cancer. Limbic encephalitis is characterized by anxiety and
depression, leading to memory loss, agitation, confusion, hallucinations, and
behavioral abnormalities. Anti-Hu antibodies, directed against RNA binding
proteins, may be present in the serum and spinal fluid. MRI may disclose
areas of increased contrast uptake and edema.
Renal paraneoplastic syndrome: Membranous glomerulonephritis may occur
in patients with colon cancer, ovarian cancer, and lymphoma as a result of
circulating immune complexes.
Rheumatologic paraneoplastic syndromes: Rheumatologic disorders
mediated by autoimmune reactions can also be a manifestation of
paraneoplastic syndromes.
Arthropathies (rheumatic polyarthritis, polymyalgia) or systemic sclerosis may
develop in patients with hematologic cancers or with cancers of the colon,
pancreas, or prostate. Systemic sclerosis or SLE may also develop in patients
with lung and gynecologic cancers.
Hypertrophic osteoarthropathy is prominent with certain lung cancers and
manifests as painful swelling of the joints (knees, ankles, wrists, elbows,
metacarpophalangeal joints) with effusion and sometimes fingertip clubbing.
Secondary amyloidosis may occur with myeloma, lymphomas, or renal cell
carcinomas.
Dermatomyositis and, to a lesser degree, polymyositis are thought to be more
common in patients with cancer, especially in those > 50 yr. Typically,
proximal muscle weakness is progressive with pathologically demonstrable
muscle inflammation and necrosis. A dusky, erythematous butterfly rash with
a heliotrope hue may develop on the cheeks with periorbital edema.
Corticosteroids may be helpful.
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Screening Procedures in Average-Risk Asymptomatic People As

Recommended by the American Cancer Society
Type of Cancer Procedure Frequency

Breast cancer Breast self-examination Monthly or periodically after age 20
Clinical breast examination Every 3 yr between ages 20 and 39, then yearly
Mammography Yearly, starting at age 40
MRI Yearly (in addition to mammography), starting at age 40
for women at high risk or with dense breasts on
mammogram
Cervical Cancer Papanicolaou (Pap) test Yearly ( or every 2 yr if the newer liquid-based test is
sometimes with the human used) in all women within 3 yr of first vaginal
papilloma virus test intercourse but no later than age 21
After age 30, every 3 yr if > 3 consecutive examinations
are normal and risk is not high
Cervical, uterine, Pelvic examination Every 1 to 3 yr between ages 18 and 40, then yearly
and ovarian
cancers
Prostate cancer Blood test for prostate-specific Yearly after age 50 (or age 45 for men at high risk)
antigen
Rectal and colon Faecal occult blood Yearly starting at age 50
cancer Or
Flexible sigmoidoscopy Every 5 yr, starting at age 50
Or
Colonoscopy Every 10 yr, starting at age 50
RADIATION THERAPY. GENERAL PRINCIPLES

Shortly after Roentgen discovered radiographs in 1895, their clinical
usefulness as a means of cancer treatment was first appreciated. Since that
time, radiation therapy has developed into a recognized medical specialty.
The Curie family discovered radium in 1898. Alexander Graham Bell
suggested its use in brachytherapy for direct implantation in malignant
tumors.The lack of a precise method of measuring dosage limited the early
use of radiation therapy. An early prescription typically called for an erythema
dose as the standard unit of radiation. One of the limiting factors in early
treatment was skin tolerance.This hurdle was overcome by Coutard's
recognition of the usefulness of fractionation, ie, dividing the dose into several
smaller increments rather than a single massive dose. At the same time, high-
energy supervoltage was developed, and later, megavoltage-dedicated
radiotherapy units were introduced.The exact mechanism of cell death due to
radiation is still an area of active investigation. A large body of evidence
supports double-stranded breaks of nuclear DNA as the most important
cellular effect of radiation. This breakage leads to irreversible loss of the
reproductive integrity of the cell and eventual cell death.Radiation damage
can be directly ionizing; however, in clinical therapy, damage is most
commonly indirectly ionizing via free-radical intermediaries formed from the
radiolysis of cellular water.Radiation can also affect the processes of the cell
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cycle necessary for cell growth, cell senescence, and apoptosis (programmed
cell death). Many of these processes are only now beginning to be elucidated
and manipulated in order to make radiation therapy more effective.The
therapeutic mechanism for radiation is based on the intrinsic ability of cells to
repair damage and the ability of the radiation oncologist to take advantage of
any geometric separation between the malignant and nonmalignant tissues.A
logarithmic curve of survival versus dose characterizes cell survival after
exposure. The curve forms an initial shoulder followed by a logarithmic
decline in survival, which varies with the dose Sublethal damage, which must
be overcome with each fraction of radiation therapy, is thought to cause the
initial shoulder. Repeated small doses of radiation are less damaging to a
sensitive cell than a single fraction of equivalent total dose Manipulation of the
cellular environment can alter the shape of the survival curve.In addition to the
intrinsic cellular radiosensitivity, cell survival is found to be related to oxygen
tension, position of the cell in the mitotic cycle, and dose rate. These features
are responsible for the 4 R's of radiobiology, namely, repair, redistribution,
repopulating, and reoxygenation.
X-Rays and gamma ray photons are part of the electromagnetic spectrum.
The dual nature of electromagnetic radiation is used to explain its wave and
particulate behavior.
A photon is a packet of energy that can be characterized by the equation E =
hv, where h is Planck's constant (6.62 X 10-34 J-sec) and v is the frequency of
the photon. Frequency is equivalent to the quotient of the speed of light (3 X
108 m/sec) divided by the wavelength. Thus, high-energy radiations have a
short wavelength and high frequency.
The interaction of a photon beam with matter results in the attenuation of the
beam. Five major types of interactions typically occur, namely, coherent
scattering, photoelectric effect, Compton scattering, pair production, and
photodisintegration. The particular type of interaction is related to photon
energy. In radiation therapy, the photoelectric effect, Compton effect, and pair
production are of interest, with the Compton effect being the predominant
interaction.
Photoelectric effect involves the interaction of the photon with the tightly
bound inner electrons and is proportional to the cube power of the absorbing
matter's atomic number. This interaction is responsible for the different
radiographic densities seen on diagnostic radiographs.
Compton effect involves interaction with outer electrons that are bound more
loosely. This effect is related to electron density and, therefore, results in
much more uniform tissue absorption than lower energy photons. In radiation
therapy, Compton effect predominates; therefore, the contrast observed on
therapy port films is inferior to diagnostic radiographs
Pair production involves interaction of the photon with the atomic nuclear
electromagnetic field. This interaction becomes significant at high energies
(>10 MeV) and is proportional to the atomic number of the absorbing matter.
Radioactive isotopes occur naturally and can be generated artificially.
Becquerel recognized radioactivity in 1896 and is honored by having the unit
of activity named after him. The activity of a radioisotope decays over time. Its
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energy spectrum, decay spectrum, and half-life characterize the isotope. A
particular isotope may decay via the production of alpha particles or beta
particles (positive or negative charge),
through electron capture, internal conversion, or a combination of these
reactions. Likewise, a nuclear transformation occurs when a chemical reaction
takes place following a nuclear reaction and results in the generation of a new
species.
Physical Characteristics of Commonly Used Isotopes:
Isotope Half-life Energy (Mev) Half-value Layer Exposure Rate Constant

(mm lead) (R/sq cm/mCi-hr)
Ra-226 1600 years 0.047-2.45 (0.83 avg) 8.0 8.25
Co-60 5.26 years 1.17-1.33 11.0 13.07
Cs-137 30 years 0.662 5.5 3.26
Ir-192 74.2 days 1.36-1.06 (0.38 avg) 2.5 4.69
I-125 60.2 days 0.028 avg 0.025 1.46
Radiation dose or exposure is measured in units of absorbed radiation per

unit of tissue. The Gray (Gy) represents 1 J/kg of tissue. Older literature uses
the rad, which is equivalent to 0.01 Gy. The exposure and dose rate of
radiation decrease according to an inverse square law, such that the
exposure decreases by 4 when the distance increases by 2.
External beam therapy is commonly delivered via a medical linear accelerator
or Cobalt-60 unit. The introduction of these megavoltage units ushered in the
modern age of radiation therapy. These units deposit the maximum dose
beneath the surface; therefore, external beam therapy is considered skin
sparing. Photons traverse the entire tissue thickness but deposit less dose as
the depth increases.
Many modern linear accelerators are also capable of producing electrons,
which can be used for treatment situations where the limited depth
penetration of these particles is useful, such as in cases where the
contralateral parotid gland must be spared The process of treatment planning
calls for an integration of the physical findings and diagnostic imaging
information with knowledge of the pertinent anatomy, pathology, and natural
history of the particular tumor type.
The radiation oncologist and other members of the multidisciplinary team
must decide if radiation will play a role in the treatment of the patient. Once
the decision is made, consideration must be given to whether the radiation is
prescribed as definitive, palliative, or adjuvant therapy, and if it will be
integrated with surgery and chemotherapy.
The radiation oncologist may recommend additional studies in the workup of
the patient or may choose to coordinate the patient's care. A detailed
knowledge of the various modalities of radiation therapy in the physician's
armamentarium together with their individual physical characteristics and
unique toxicities is essential.
Contemporary treatment-planning computers allow for the incorporation of 3-
dimensional anatomic data to be used for planning of radiation fields. Using
beam's-eye-view technology, the field of radiation can be planned so that the
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physician is assured that the radiation field adequately covers the target and
spares or minimizes the dose to the nontarget healthy tissues. Complex beam
arrangements can be used with the knowledge that a geometric miss can be
avoided. An entire lexicon of treatment-planning terminology has been
created as a result.
The physician uses the clinical and radiographic findings to determine the
gross tumor volume (GTV). Next, the clinical tumor volume (CTV) is defined to
include microscopic extension of the disease. The planning treatment volume
(PTV) allows for day-to-day variation.
In order to minimize any variation in patient positioning, meticulous
immobilization is essential. Thermoplastic masks and other similar positioning
devices frequently are used in the treatment of head and neck cancer.
Conventional fractionation in the United States is considered to be 1.8-2 Gy
per day, administered 5 days each week for 5-7 weeks, depending on the
particular clinical situation. The alteration of this scheme has been evaluated
for a variety of reasons, including time constraints, staff constraints, machine
availability, and patient convenience.A variety of methods have been used to
correlate different dose-fractionation schemes. These methods are rooted in
an understanding of the dose-response curves and the association (or lack
thereof) between acute reaction and long-term sequelae of
treatment.Strandquist produced the first clinical isoeffect curve. He calculated
the relationship between time, dose, cure, and skin reactions in the treatment
of skin cancers. Later, Ellis recognized that the time factor was actually
dependent on both the overall treatment time and the number of fractions. He
devised the nominal standard dose (NSD) formula, ie, D = NSD X N 0.24 X
T0.11, where D = dose, N = number of fractions, and T = overall time.These
formulas have been used in an attempt to adjust for the alterations in the
standard fractionation schemes. Most contemporary isoeffect formulas make
use of the linear-quadratic model as a basis for dose adjustments, ie, D1/D2 =
fraction. This formula assumes a complete repair of sublethal damage

between the fractions. The major deficiency with these formulas is the lack of
individual variations.
One of the early attempts at altered fractionation was the use of split-course
therapy. The attempt was to attain comparable or better levels of tumor
control by allowing reoxygenation with reduced acute toxicity. A 2- to 3-week
rest from the treatment was often used. However, this rest period resulted in
poorer long-term control because repopulation and accelerated repopulation
dominated.
Other fractionation schemes include hyperfractionation, hypofractionation, and
accelerated fractionation. In hyperfractionated regimens, the goal is to deliver
higher tumor doses while maintaining a level of long-term tissue damage that
is clinically acceptable. The daily dose is unchanged or slightly increased
while the dose per fraction is decreased, and the overall treatment time
r the tumor must be greater than that of the
dose-limiting tissue.
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An additional rationale for hyperfractionation is to allow radiosensitization
through redistribution. With a greater number of fractions, the likelihood is
greater that the tumor will be in a sensitive phase of the cell cycle at some
time during the treatment. This strategy invariably results in more intense
acute reactions when compared to conventional treatment.
In the accelerated fractionation schemes, the dose per fraction is unchanged
while the daily dose is increased, and the total time for the treatment is
reduced. Three basic variations are possible.
Continuous hyperfractionated accelerated radiation therapy (CHART) is an
intense schedule of treatment, where multiple daily fractions are administered
within an abbreviated period of time. An intense acute reaction develops in
most patients. This reaction usually limits the total dose.
In a concomitant boost technique, the first fraction of the day is administered
in a larger volume, while the second fraction is targeted to a reduced-boost
field of treatment. The boost may be administered early in the course of
therapy or toward the end of treatment. This regimen is based upon the
recognition that the treatment can induce an accelerated repopulation of the
tumor cells so that reduction of the overall treatment time results in improved
control.
Clinical trials are in progress with the goal of evaluating these various altered
fractionation patterns and comparing them to conventional treatment. Results
from the recently completed randomized trial, RTOG-9003, supports the
benefit of altered fractionation over conventional treatment for head and neck
cancer. So far the benefit seems to be in local regional control. Further follow-
up is necessary to determine if there is an overall survival benefit as
well.Radiation effects on the normal tissues are divided into acute and chronic
effects. Acute effects occur during the course of therapy and during the
posttherapy period (approximately 2-3 weeks after the completion of a course
of irradiation). Chronic effects can manifest anytime thereafter, from weeks to
years after the treatment.
Patients are usually most bothered by the acute effects, but physicians are at
least equally concerned about the chronic effects. The acute effects can be
quite uncomfortable but generally resolve. The chronic effects can be
devastating, permanent, and progressive.
Much of the effort that goes into the treatment planning regards minimizing
the normal tissue effects of treatment. The tissues that divide rapidly (eg,
mucous membranes) respond acutely to radiation and are responsible for
much of the acute morbidity of the treatment.
Two major theories are used to explain late injury. One theory attributes
chronic injury to the damage of the microvasculature, while the other
attributes injury to stem cell depletion.
The mucous membranes of the oral cavity and the oropharynx respond early
to fractionated radiation. Erythema is often evident after 1 week of treatment
at conventional doses. This condition progresses over the next few weeks
through various stages of mucositis, ranging from small patches to confluent
or even ulcerated areas.
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Mucositis represents caking of the dead epithelial cells, fibrin, and
inflammatory cells. Consider superimposed infection with yeast species or
bacteria when patients report oral or throat pain during treatment. Healing
begins while the patient is still undergoing treatment but may continue for
several weeks after the radiation is completed.
Loss of taste is a common acute effect of treatment. Taste loss begins early
and progresses rapidly during the second 2 weeks of treatment. Patients may
report diminished acuity, odd sensation, or complete absence of taste.
Xerostomia is often present and exacerbates this loss of taste. This condition
is often accompanied by a loss of appetite and weight loss. Recovery of taste
is a slow and, frequently, an incomplete process.
The major salivary glands (ie, parotid and submandibular glands) are
responsible for nearly 80% of salivary production. The parotid glands primarily
consist of serous acini, while the submandibular glands produce mucinous
and serous secretions. The minor salivary glands, which are distributed
throughout the oral mucosa, produce mostly mucinous secretions.
Radiation affects the saliva volume and production and also alters the
composition of the saliva. Decreased salivary pH and decreased volume are
significant contributors to the altered oral mucosal flora and predispose
patients to caries. Salivary production decreases rapidly with treatment,
declining by nearly 50% after a week of treatment. Patients frequently
describe thickened, tenacious, ropy saliva, which may make speech difficult in
addition to affecting swallowing and taste.
High-energy radiographs are skin sparing. Skin reactions, which were at one
time dose limiting, are rarely a problem when high-energy radiographs are
used. While erythema is common after several weeks of radiation, severe skin
reactions, such as those observed in the orthovoltage era, are uncommon.
When a need for skin irradiation exists (eg, skin involvement by the tumor or
skin as the target in the treatment of basal cell cancers), the technique is
adjusted so that a brisk skin reaction is produced. The use of less-penetrating
orthovoltage radiographs, treatment with electrons, or the addition of tissue-
equivalent bolus material placed over the radiation field can circumvent skin
sparing.
Even with megavoltage treatment, skin tanning and dry desquamation can
occur. The addition of certain chemotherapeutic drugs can enhance skin and
other effects. Radiation can induce melanin production, which is often first
observed in the skin follicles because these skin invaginations receive a
slightly higher dose as the beam enters tangentially to the surface. Skin
sensitivity is increased because of the treatment.
In situations where the skin is denuded, known as moist desquamation, the
area must be kept clean to avoid superinfection. Re-epithelization moves
centrally from the field edges and is generally completed within 3 weeks prior
to the completion of treatment.
Sweat glands and sebaceous glands may cease functioning, but the in-field
hair loss usually is temporary. Regrowth is evident within a few weeks after
cessation of therapy.The late effects of radiation can be a source of ongoing
morbidity from a course of radiation therapy. Just as with the acute effects,
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the chronic effects are related to site, dose, volume, and time. Other
therapies, such as surgery and chemotherapy, can increase the probability
and severity of radiation-related morbidity.High doses of radiation to the neck
can result in fibrosis. This condition is especially true in the postoperative
setting where the neck may develop a woody texture and have limited
movement. Likewise, the masticatory muscles may develop fibrosis, which
can result in trismus. Instruct patients to begin stretching exercises of their jaw
muscles as soon as possible after surgery.
Obstruction of the cutaneous lymphatics results in lymphedema, which may
be associated with episodes of intermittent erysipelas.
Delayed wound healing can be a consequence of high-dose preoperative
radiation.
Telangiectasis may appear some time after the treatment in the areas that
were treated without skin-sparing techniques such as with electrons,
tangential irradiation, and deliberate addition of bolus material.
The loss of salivary function is usually complete after modest doses of
radiation to the parotid glands. The basal flow rates correlate with the
response to radiation therapy. With 40-60 Gy, fewer than 20% of patients
have a measurable salivary flow. For patients receiving fewer than 30 Gy,
some function may return after 6-12 months. However, at dose levels
exceeding 50 Gy, xerostomia usually is irreversible.
Dry mouth is probably the most common problem for patients who receive
therapeutic doses of radiation. Numerous approaches have been tried to
address this problem. Pilocarpine 5 mg tid has been shown to stimulate
residual salivary function. Some patients use artificial saliva substitutes, but
most patients find them inadequate. Many patients must carry bottles of water
to provide some relief.
The US Food and Drug Administration (FDA) has recently approved the use
of IV Amifostine (Ethyol) as a radioprotectant agent. Administered as a daily
dose, Amifostine is to be used in the prevention of radiation-induced
xerostomia in the postoperative setting. Concern about tumor protection
appears to be unwarranted. Adverse effects, such as nausea and
hypotension, the need for daily injections, and cost concerns may limit its wide
acceptance. SQ administration, while not a labeled use, seems to be equally
effective and associated with less toxicity.
Intensity modulated radiation therapy (IMRT) is an increasingly available,
novel approach to preventing xerostomia. At the time of treatment planning,
the radiation oncologist uses an inverse-planning algorithm that allows
selective avoidance of critical normal tissues without compromising the tumor
doses. Other potential uses for IMRT include the ability to administer
biologically higher doses to target tissues and biologically lower doses to
nontarget tissues and thus increase the therapeutic ratio.
Several planning systems and systems of delivery are currently available or
are in the testing phases. The initial reports are encouraging.
As a consequence of oral pain and altered diet during treatment and
xerostomia following treatment, the oral flora and pH can be altered
significantly. Without meticulous dental care during and after radiation
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therapy, patients are prone to accelerated caries and decay. Oral and gingival
tissue may atrophy following radiation, which results in a thin pale layer with
evidence of telangiectatic vessels.
Ulceration and bone exposure can occur. If serious injury to the underlying
bone occurs, osteoradionecrosis may follow. Fortunately, this complication is
uncommon. When it does occur, management of the condition may be
difficult. While patience is important, some cases require intervention, which
includes the use of antibiotics, hyperbaric oxygen treatment, and resection.
Radiation to the spinal cord may result in a self-limited transverse myelitis,
known as Lhermitte syndrome. The patient notes an electric shocklike
sensation that is most notable with neck flexion. Rarely does this condition
progress to a true transverse myelitis with associated Brown-Squard
syndrome. The dose to the spinal cord must be limited so as to avoid this
devastating complication.
A course of treatment often affects the thyroid gland either directly or
secondarily via the hypothalamic-pituitary axis. Chemical hypothyroidism is
often the only manifestation of an endocrinopathy and is treated readily with
supplemental thyroid preparation. Other endocrinopathies are uncommon.
Other structures that must be considered during the treatment planning are
the visual apparatus, the auditory apparatus, and the apex of the lungs.
Exceeding the tolerance of the lacrimal gland can result in dry-eye syndrome.
The lens is highly sensitive to radiation. Direct irradiation of the lens with the
most commonly used therapeutic doses results in cataract formation.
Tolerance of the retina and optic nerve must also be respected during the
treatment planning to avoid visual loss.
Radiation to the auditory apparatus may result in serous otitis or possible
sensorineural hearing loss at high doses of irradiation.
Radiation-induced cancers are fortunately quite uncommon following
therapeutic doses of radiation. A much greater risk of second malignancy is
due to the same etiologic and genetic mechanisms that are responsible for
the primary tumor.Chemotherapy can enhance the effects of radiation
therapy. Numerous agents have ben used either sequentially or concurrently
with radiation. Most studies indicate that the best results can be obtained with
concurrent radiation and platinum-based chemotherapy. The concurrent use
of chemotherapy also intensifies the acute toxicities of treatment, and patients
often require nutritional support during therapy. Recent encouraging data
are being used to define a role for induction chemotherapy followed by
concurrrent chemoradiotherapy. Other agents that are used in head and neck
cancer include fluorouracil, paclitaxel (Taxol), docetaxel (Taxotere), and
hydroxyurea.
Biological agents are being studied that may reduce some of the toxicities of
combined chemotherapy and radiation or enhance the effect of radiation
therapy. Keratinocyte growth factor (KGF) has been found useful in reducing
mucosal toxicity in patients undergoing total body irradiation and may be
useful in other applications as well. Targeted therapies that act to interrupt
signal transduction pathways are also being studied. Dramatic results with the
epidermal growth factor receptor (EGFR) antibody cetuximab has resulted in
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recent FDA approval of this agent for use in head and neck cancers.
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CHAPTER 21
SURGERY CLERKSHIP MANUAL.
OBJECTIVES.
1. Medical knowledge.
natural history of diseases of surgical importance.
Indications for surgery and its limitations in disease management and
role of non-operative therapy.
2. Interpersonal and communication skills.
Effective communication with patients, families and health care team
members.
3. Scientific foundation of surgery.
Knowledge of current scientific foundation (both basic and behavioural
sciences) in relation to surgical diseases and development of a patient
management plan.
4. Basic clinical skills.
Develop skills in obtaining a good history and performing a
comprehensive physical examination.
Develop skills in the selection, performance and interpretation of
appropriate clinical procedures, imaging studies and laboratory tests.
Develop skills in giving an oral case presentation.
5. Patient care.
Develop skills in making an accurate diagnosis and a management
plan that incorporates disease prevention.
6. Community health.
Knowledge of social and community aspects of health care in Kenya.
7. Medical ethics.
Knowledge of ethical issues related to patient management.
8. Professionalism
Aim to act with honour and integrity in professional and personal life.
Demonstrate caring and compassion for patients and for members of
the health care team.
Respect patients rights and wishes.
Act in respectful manner toward faculty, colleagues and staff.
Provide good leadership in interactions with, and development of,
others.
9. Lifelong learning.
Demonstrate skills of self-education and lifelong learning.
PHYSICAL EXAMINATION SKILLS.
186
(1) GOAL
The broad goal of the teaching of postgraduate students in Principles of
Surgery is to produce surgeons capable of delivering efficient surgical care.
(2) OBJECTIVES:
2.1 Knowledge
At the end of the course the resident shall be able to:
2.1.1 describe aetiology, pathophysiolgy, principles of diagnosis and
management of common surgical problems including
emergencies in adults and children.
2.1.2 define indications and methods for fluid and electrolyte
replacement therapy including blood transfusion;
2.1.3 define asepsis, disinfection and sterilization and recommend
judicious use of antibiotics;
2.1.4 describe common malignancies in the country and their
management including prevention;
2.1.5 enumerate different types of anaesthetic agent, their indications,
mode of administration, contraindications and side effects.
2.2 Skills
At the end of the course, the resident should be able to:
2.2.1 diagnose common surgical conditions both acute and chronic, in
adult and children.
2.2.2 plan various laboratory tests for surgical conditions and interpret
the results;
2.2.3 identity and manage patients of haemorrhagic, septicaemic and
other types of shock;
2.2.4 be able to maintain patient air-way and resuscitate;
(a) a critically injured patient:
(b) patient with cardio respiratory failure.
(c) drowning case.
2.2.5 monitor patients of head, chest, spinal and abdominal injuries,
both in adults and children;
187
2.2.6 provide primary care for a patient of burns;
2.2.7 acquire principles of operative surgery, including pre-operative,
operative and postoperative care and monitoring.
2.2.8 treat open wounds including preventive measures against
tetanus and gas gangrene;
2.2.9 diagnose neonatal and paediatric surgical emergencies and
provide sound primary care.
2.2.10 Identity congenital anomalies and plan the appropriate
management.
(3) THEORY
3.1 History & Development of Modern Surgery & Science:
3.1.1 Wound healing: Types of wound; biological process of
healing; factors influencing healing.
3.1.2 Road traffic injuries First aid resuscitation, Assessment &
management.
3.1.3 Civilian injuries Triage, first aid, hospital management.
3.1.4 Missle injuries Mechanism of blast injuries, management.
3.2 Fluid & electrolytes & A/B Balance:
3.2.1Physiology and fluid compartments of body.
3.2.2Clinical features of Sodium, Potassium, Fluid loss and its
management.
3.2.3 Parenteral fluid therapy types, indications, contra-
indications.
3.3 Metabolic Acid / Base Balance:
3.3.1 Alkolosis types, clinical situation & management.
3.3.2 Acidosis Type, clinical situations & management.
3.4 Haemorrhage:
3.4.1 Type, recognition of haemorrhage, clinical features of
assessment of blood loss and treatment.
3.4.2 Transfusion of blood & blood products, storage, complications
of transfusion, blood substitutes.
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3.4.3 Surgically related bleeding disorders.
3.5 Shock
3.5.1 Types of shock & classification

3.5.2 Pathophysiolgy of shock
3.5.3 Diagnostic method and assessment
3.5.4 Clinical monitoring & management
3.5.5 Crush Syndrome
3.5.6 Septicemia
Multi organ failure syndrome (MOFS)
3.6 Nutrition
3.6.1 Malnutrition hypercatabolic state in sepsis effects of

malnutrition.
3.6.2 Assessment of nutrition and management.
3.6.3 Type of feeding: external & parenteral.
3.7 Wound infection: -
3.7.1 Source of sepsis, spread, anaerobic infection.
3.7.2 Hospital based infection (Nosocomial).
3.7.3 Prevention and principles of antimicrobial therapy.
3.7.4 Cellulitis, lymphangitis, abscess, boil, carbuncle.
3.7.5 Specific infections.
(a) Tetanus
(b) Gas gangrene
(c) Mycobacterial - (i) Tuberculosis
(ii) Leprosy
(d) Syphilic infection.
(e) Actinomycosis
3.7.6 HIV & AIDS
3.7.7. Infections of hand
(a) Surgical anatomy of spaces of hand.
189
(b) Acute paronychia, terminal pulp space infection.
(c) Acute suppurative tenosynontes.
(d) Deep palmar spaces and infections.
(e) Principles of management.
(f) Surgical management.
3.7.8.Foot
(a) Ingrowing toe nail.
(b) Madura foot
(c) Diabetic & foot problems.
3.8 Tumours in Surgery
3.8.1 Benign, malignant tumours, premalignant conditions.

(a) Carcinoma- Sq. Cell carcinoma, basal cell carcinoma,
Malignant melanoma
(b) Ulcers- Types of ulcers
(c) Cysts - Classification, sebaceous cyst, dermoid.

(d) Fistular - Definition, types of fistular.
- Causes of fistulae persisting
- Sinuses.
(4) THEORY
4.1 Arterial Disease:
Types of arterial occlusion:
4.1.1 Signs of arterial occlusions.
4.1.2 Clinical of features of arterial occlusion
4.1.3 Investigations of arterial occlusion
4.1.4 Management of arterial occlusions:
(a) Non operative
(b) Operative
4.1.5 Embolic phenomenon and management
190
4.1.6 Air embolism, fat embolism
4.1.7 Gangrene
(a) Types of gangrene
(b) Causes
(c) Treatment of gangrene
4.1.8 Aneurysms
(a) Types, Symptoms
(b) Abdominal aneurysms
(c) Peripheral aneurysms
(d) Dissecting aneurysms
(e) A. V. Fistula
4.1.9 Cervical rib (Thoracic outlet syndrome)
4.1.10 Burgers diseases
4.1.11 Raynauds disease
4.1.12 Sympathectomy
4.2 Venous Disorders:
4.2.1 Investigations of venous disorders Invasive; Non invasive.
Superficial or deep vein thrombosis:
4.2.2 Prevention of deep vein thrombosis, treatment.
4.2.3 Varicose veins Symptoms, complications, clinical tests,

management.
4.3 Lymphatics:
4.3.1 Acute lymphangitis
4.3.2 Chronic lymphadenopathy & differential diagnosis
4.3.3 Lymphoedema, types Congenital acquired.
4.3.4 Investigations; - Treatment.
4.4 Lymphadenopathy: -
4.4.1 Acute lymphaadenopathy
4.4.2 Chronic Lymphadenopathy & differential diagnosis
191
4.4.3 Lymphoma Hodgkins
4.4.4 Non Hodgkins
(5) THEORY
5.1 Non malignant lesions of mouth, cheek and tongue
Stomatitis - Infections organisms, predisposing factors. Types of

Stomatitis.
Herpes infection, monilial infection, aphthous stomatits

- Differential diagnosis of ulcers to tongue
- Hyperkeratous. Leucoplakia
Ranula, subingual dermoid tongue-tie. Epulis.
5.2 Salivary Gland :

5.2.1 Surgical anatomy of parotid gland.
(a) Acute parotitis
(b) Submandibular calculous
(c) Parotid fistula.
5.2.2Classification of salivary gland neoplasm
(a) Clinical features, management of pleomorphic adenoma.
(b) Adenolymphoma
5.2.3 Freys syndrome, Sjogrens syndrome, mikuliez disease, sialosis
5.3 Breast :
5.3.1 Surgical anatomy Investigations discharges from Nipple
5.3.2 Mastitis types
5.3.3 Cystic swellings of the breast.
5.3.4 Classification & types.
5.3.5 Fibroadenoma including cystosarcoma phylloides, fibroadenosis
5.3.6 Carcinoma breast
(a) Etiology, Pathologic types, spread.
(b) Investigations staging, treatment.
192
5.3.7 Breast reconstruction
(a) Carcinoma male breast.
(b) Gynaecomastia.
5.4 Neck :
5.4.1 Thoracic outlet syndrome
(a) Various causes Cervical rib (Major)
(b) Other causes (Short notes)
5.4.2 Discuss D/ D midline swelling in the neck + Thyroglossal fistula
5.4.3 Discuss D/ D swellings in the Ant. Triangle neck cold abscess,
branchial cyst. Branchial fisula, Carotid body tumour etc.
5.4.4 Discuss D/ D swelling posterior triangle (including occult primary
with secondaries and pancoast tumour.)
5.4.5 Management of lymphnode secondaries in neck.
(a) Investigations
(b) Block dissection
5.5 Endocrines : Thyroid gland
5.5.1 Surgical anatomy, physiology, thyroid function tests.
5.5.2 Details history taking and clinical examination of thyroid gland.
5.5.3 Classification of goitre.
(a) Types Puberty goitre
(b) Iodine deficiency.
(c) Colloid.
5.5.4Thyrotoxicosis
(a) Primary (b) Secondary
Toxic nodule Other causes.
5.5.5 Classification of thyroid neoplasms. Papillary, follicular,
anaplastic, medullary.
5.5.6 Thyroiditis, complications of thyroidectomy Ectopic thyroid &
anamalies of the thyroglossal tract.
5.6 Parathyroid & Adrenal Glands:
5.6.1 Surgical anatomy, physiology of parathyroid.
193
5.6.2 Clinical features and management of
(a) Hyperparathyroidism
(b) Short note on hypoparathyroidism
5.6.3 Cushings syndrome
(a) Phaeochromocytoma
(b) Neuroblastoma.
(6) THEORY
6.1 Oesophagus:
6.1.1 Surgical Anatomy, Physiology
6.1.2 Investigations - Ba. Swallow, oesophagoscopy
6.1.3 Hitaus Hernia - Types Clinical features, Investigations,
Treatment.
6.1.4 Reflux oesophagitis
6.1.5 Pulmmer Vinson Syndrome.
6.1.6 Injuries - Perforation, Chemical burns, Corrosives, Causes
& Management.
6.1.7 Achalasia Cardia - Aetiology, Clin. Features, Investigations,
Treatment.
6.1.8 Diff. Diagnosis of dysphagia.
6.2 Stomach & Duodenum:
6.2.1 Gastric function tests, Investigations Gastroscopy, Ba. Meal
Peptic ulcer Chronic duodenal Ulcer- aetiology, Clinical
features, Investigations, treatment. Medical and surgical. Chronic
gastric ulcer. Aetiology, Clinical features, treatment.
6.2.2 Complications of peptic ulcer perforation clinical features,
investigations, treatment.
(a) Haemorrhage Treatment
(b) Pyloric stenosis clin. Features, investigations.
(c) Electrolyte disturbances, treatment.
6.2.3 Complications of surgery for Peptic Ulcer.
194
(a) Anastamotic ulcer
(b) Dumpting syndrome.
6.2.4 Carcinoma of stomach Aetiology pathology clin. Features.
Investigations, treatment.
6.2.5 Upper G. I. Bleeding - Causes D. D. and treatment.
6.3 Liver:
6.3.1 D. D. Hepatomegaly
6.3.2 Injuries
6.3.3 Liver abscess Pyogenic Amoebic

6.3.4 Hydatid cysts.
6.3.5 Portal hypertension Investigations, Surgical treatment
(a) Bleeding varices Management.
6.3.6 Tumours Secondaries
(a) Hepatoma.
(7) THEORY
7.1 Spleen
7.1.1 Anatomy effect of splenectomy

7.1.2 Injuries - Rupture
7.1.3 Splenomegaly Causes
7.1.4 Hereditary spherocystosis
7.1.5 I.T. Purpura
7.1.6 Hypersplenism
7.1.7 Splenectomy Indications.
7.2 Gall Bladder & Bile Ducts : Anatomy

7.2.1 Investigations OCG, Ultrasound, operative Cholangiogram.
7.2.2 T. Tube, Cholangiogram, ERCP.
7.2.3 Choledochal cyst.
7.2.4 Gall Stones, Types: Causative features, effects of Gall stones.
195
7.2.5 Choleystitis Aetiology, Clinical features, Investigations,
Treatment, Complications.
7.2.6 C.B. D. Stone Clin. Features; Courvoisiers law. Investigations,
Treatment
7.2.7 Obstructive jaundice, Diff. Diagnosis and management.
7.3 Pancreas :
7.3.1 Pancreatitis, Classification
7.3.2 Acute pancreatitis Aetiology, Pathology, Clinical features,
Investigations, and Management.
7.3.3 Complications of Pancreatitis Pseudocyst.
7.3.4 Chronic pancreatitis Aetiology, Clinical features, Pathology,
Investigation, Treatment.
7.3.5 Carcinoma pancreas Pathology, Clinical features,
Investigations and Treatment. Insulinoma.
(8) THEORY
8.1 General Surgery:
8.1.1 Injuries:
8.1.2 Diverticular - Meckels diverticulum
- diverticulosis of colon Aetiology
- Clinical features, Investigations, treatment
8.1.3 Ulcerative colitis - Aetiology, Pathology, Clinical features.
- Investigations and treatment.
8.1.4 Amoebiasis
8.1.5 Typhoid complications perforation, management.
8.1.6 Crohns disease:
8.1.7 Tuberculosis - Types, Clinical features, Investigations
- Treatment Medical Surgical.
8.1.8 Tumours of small intestine Carcinoid, peulz Jughers
Enterocutaneous fistula
196
8.1.9 Intestinal obstruction Types, Pathology, Clin. features of Ac.
Intestinal obstruction,
Investigations, Treatment of Intestinal obstruction.
8.1.10 Special types of Int. Obstruction Pathology & Management .
Intussusception, adhesions, bands & structures, Paralytic ileus.
8.1.11 Lower G. I. Bleeding Causes, Investigations, and Management.
(9) NEUROSURGERY
9.1 Head Injury:
Introduction classification, pathophysiolgy, basic dynamics of
injury Intracranial hematomas & Management of
unconscious patients with enclosed head injury.
9.2 Infections of CNS
Surgical aspects with specific emphasis on subdual emphyema,
brain abscess and management of the sequalae of the different
types of infections.
9.3 Hydrocephalus:
Classification anatomy & Physiology of cerebro spinal fluid
formation, circulation of absorption, clinical features,
Investigations and management Hind brain anomalies.
9.4 Spinal Dysraphism :
Basic Embryology Pathology anatomy Clinical features and
principles of management of different types of spinal dysraphism.
9.5 Intracranial Space Occupying Lesions
Signs and symptoms of ICT, Classification of Br. Tumours,
Investigations, Principles of Surgical management of diff. Tumours.
9.6 Spinal Compression:
Classification, pathophysiology, Clinical features and management.
9.7 Cervical & Lumbar disc diseases Clinical features and
management.
9.8 Pain
197
Pathway Surgical aspects of pain management. Trigeminal
Neuralgia.
9.9 Subarchnoid Haemorrhage:
Clinical features immediate management and brief idea about
surgical management of spontaneous intracerebral / cerebellar
haematomas, aneurysms and AVMS.
9.10 Various investigations in the diagnosis of intracranial & Spinal
lesions.
(10) UROLOGY
10.1 Introduction Urological symptomatology & Investigations.
10.2 Anomalies of the upper urinary tract.
10.3 Anomalies to lower urinary tract.
10.4 Urological trauma Upper urinary tract.
10.5 Urological trauma Lower urinary tract & Structure of Urethra.
10.6 Urinary tract infections.
Genito Urinary Tuberculosis
10.7 B. P. H.
10.8 Carcinoma Prostate
10.9 Retention of Urine Causes & Treatment.
10.10 Urolithiasis
10.11 Testicular tumour, Foumiers Gangrene.
10.12 Hydrocele, undescended testis, spermatocoele, varicocele,
Epididymo-orchitis.
10.13 Penile malignancy Phimosis, Paraphimosis.
10.14 Approach to infertility.
10.15 Principles of renal transplants.
Medication, preparation of donar, recipient complications of
rejection.
(11) SURGICAL ONCOLOGY
11.1 Basics : Hyperplasia, dysplasia, carcinoma in situ, invasive
tumour. Characteristics of benign and malignant
198
neoplasm Carcinoma, Sarcoma, methods of spread &
available modalities of cancer. Staging of malignant
tumours.
Premalignant condition of neoplasm.
11.2 Specific topics
11.2.1 Skin Malignant tumours

(a) Sq. Cell carcinoma
(b) Malignant Melanoma
(c) Basal cell carcinoma
11.2.2 Oral malignancy
(a) Benign lesions : Leucoplakia
(b) Invasive tumours : Buccal mucosa
- Carcinoma tongue
11.2.3 Investigations and management.
11.2.4 Jaw tumours
(a) Benign & malignant
(b) Carcinoma of maxilla
11.2.5 Soft tissue Sarcomas
(12) PLASTIC SURGERY
12.1 Congenital anomalies of Head and Neck including cleft tip &
palate
12.2 Burns.
12.3 Vascular lesions of Head and Neck
12.4 Skin cover
12.5 Head injuries
12.6 Introduction to cosmetic surgery.
12.7 Maxillofacial injuries including soft tissue injury of face.
12.8 Lymphedema.
12.9 Pressure sores (Bed sores)
(13) THEORY
199
13.1 Operative Surgery
13.1.1 Introduction and General principles including suture
materials.
13.1.2 Skin and subcutaneous Tissue.
(a) Incision & drainage abscess (Hitons method, Cold
abscess)
(b) Excision of swelling lipoma, sebaceous cyst.
(c) Biopsy of lymphnode Tuberculosis
13.1.3 Vessels - Venesection
Trendelenbergs op. & stripping of veins.
13.1.4 Hands & Feet - Pulp space infection Paronychia
Ingrowing toe nail.
13.1.5 Amputation - General principles Symes Below
knee
13.1.6 Head - Scalp wound sutures.
13.1.7 Amputation - General Principles Symes Below
knee
13.1.8 Head - Scalp wound sutures
Burrhole Subdural & extradural
haematoma
13.1.9 Neck - Tracheostomy Thyroidectomy
Block dissection.
13.1.10 Breast - Abscess drainage Fibroadenoma excision
Mastectomy simple, Radical.
13.1.11 Abdomen - Abdominal incisions Gastrostomy
G. J. Vagotomy, H. S. V. Gastrectomy.
Spleenectomy, Cholecystectomy, C. B. D.
Exploration
Appendicectomy, Colostomy,
Hemicolectomy.
200
13.1.12 Genito Urinary Tract Circumcision, hyrdocele
Orchidectomy, Partial & total amputation penis

- Inguinal Hernia Repair.
(14) THEORY
14.1 CARDIOVASCULAR & THORACIC SURGERY
14.1.1 Management of Chest injury.
14.1.2 Surgery of the diaphragm.
14.1.3 Surgery of Lung (Tumours)
14.1.4 Surgery of the chest wall (Deformitis, Tumours)
14.1.5 Surgery of the pleura (Pneumothorax Empyema)
14.1.6 Surgery of the Lung (Pulmonary Tuberculosis)
14.1.7 Surgery of the Lung (Bronchiectasis & Lung Abscess)
14.1.8 Thoracic outlet syndrome.
14.1.9 Lower limb Ischemia.
14.1.10 Surgery of the aorta and its major branches.
14.1.11 Surgery of the Mediastinum (Tumours)
14.1.12 Surgery of congenital heart disease.
14.1.13 Surgery for acquired heart disease.
14.2 PAEDIATRIC SURGERY
14.2.1 Congenital pyloric stenosis.
14.2.2 Duodenal obstruction.
14.2.3 Small intestinal obstruction in new born.
14.2.4 Hirschsprungs disease.
14.2.5 Anorectal malformation.
14.2.6 Intussusceptions.
14.2.7 Causes of intestinal obstruction in older child.
14.2.8 Hernia / Hydrocele
14.2.9 Undescended testis / Hydrocele
14.2.10 Oesophageal atresia/ Cong. Diaphragmatic hernia.
14.2.11 Childhood tumour.
14.2.12 Jaundice.
201
14.2.13 Abd. Wall defects.
14.2.14 Head and neck lesions.
14.2.15 Fluids & Electrolytes
14.2.16 Haemangiomas / Lymphangiomas.
14.2.17 C. N. S. Problems.
14.2.18 Congenital urological lesions.
(15) THEORY
15.1 Tumours of large intestines.
15.1.1 Benign
15.1.2 Familial adenomatous polyposis of colon.
15.1.3 Malignant Tumours.
15.1.4 Pathology, spread, Clinical features.
15.1.5 Investigations and management
15.2 Volvolus of colon.
15.3 Mescenteric vascular thrombosis and embolism
15.4 esenteric vascular thrombosis and embolism
15.5 Subphrinic space Anatomy
15.5.1 Clinical Features.
15.5.2 Management.
(16) THEORY
16.1 Appendix Surgical anatomy
Acute appendicitis aetiology, Clin. Features.

P. R. & Proctoscopy & Sigmoidoscopy
Injuries.
Prolapse partial & complete Treatment.
16.2 Tumours of Rectum Benign Polyps.
Carcinoma Aetiology, Pathology, Clin. Features.
Investigations, Staging, Treatment.
16.3 Anal Canal Pilonidal sinus
Fissure in ano. Haemorrhoids.
202
Anorectal abscess Classification, Treatment.
Clinical Features.
Fistula in Ano Classification, Clin. Features,
Treatment.
16.4 D. D. Bleeding P. R.
16.5 Malignant tumours of anal canal.
Pathology, Clin. Features, Treatment
16.6 Peritoneum -Omentum, mesentery, retroperitoneum.
Acute peritonitis Causes, Pathology, Clin. Features,
Investigations, Treatment.
Intra abdominal abscess Subdiaphragmatic Pelvic.
Special types of peritonitis.
16.6.1 Post operative Biliary Primary
16.6.2 Pneumococcal,
16.6.3 Post abortion Tuberculous.
16.7 Peritoneoscopy
16.8 Mesenteric lymphadenitis Non-specific Tuberculosis
Mesenteric cysts.
16.9 Basics in immunology General principles of
Transplantation, renal hepatic transplants.
16.10 Immunosuppression, drug - used.
203
204

Revision Notes for MMed Neurosurgery (UoN

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Revision Notes in Scientific Principles of Surgery for MMed Neurosurgery (UoN)

Prof N J M Mwangombe, Professor of Surgery, University of Nairobi

Every man/woman owes it as a debt to his/her profession to put on record

Francis Bacon (1561-1626)

Prof Nimrod Juniahs Mwakitawha Mwangombe MBChB, MMed, PhD (Lond)

PRE-OPERATIVE ASSESSMENT AND PREPARATION OF THE SURGICAL

Perform a pre-operative examination of patient for medical conditions

Table 1. Indications for preoperative investigations

Pre-operative investigations cannot screen for asymptomatic disease and

The National Institute for Clinical Excellence (NICE) guidelines on

Important factors in doctor-patient relationship and patient management

Information required for valid consent:

In an emergency a life-saving procedure can be performed without consent

Premedication: administration of drugs prior to an anaesthetic. Has three

Drugs used in premedication should be able to achieve the following;

Induction. Induction agents are usually administered intravenously and

Rapid induction of anaesthesia.

RISK ASSESSMENT AND MANAGEMENT

Table 2. American Society of Anesthesiologists (ASA) Classification of Physical Status

ASA Grade Definition Mortality (%)

Table 3. Application of ASA Grading. Cardiovascular disease

ASA Grade 2 ASA Grade 3

Table 4. Application of ASA Grading. Respiratory disease

ASA Grade 2 ASA Grade 3

ABBREVIATED INJURY SCALE (AIS) AND INJURY SEVERITY SCORE

Injury AIS score

Table 5. Examples of AIS scores

System Example AIS Square

Table 6. Mortality (%) according to ISS and age

ISS Mortality (%) Mortality (%) Mortality (%)

REVISED TRAUMA SCORE

Table 7. Revised Trauma Score

Parameter Finding Points

TESTS OF RESPIRATORY, CARDIAC AND RENAL DISEASE

Useful radiological investigations include chest x-ray and high-resolution

a) Spirometry: Lung volumes are assessed with spirometry

Lung function can be classified as:

OUTCOME ASSESSMENT IN NEUROSURGERY

(ii) The Glasgow outcome scale for head injuries

Table 9 Glasgow outcome scale

MANAGEMENT OF MEDICAL CONDITIONS IN SURGICAL PATIENTS

The following conditions may increase anaesthetic risk to the patient;

(I). Cardiovascular disease.

(II). Respiratory disease

(V). Obstructive Jaundice

(VI). Chronic renal failure

METABOLIC RESPONSE TO TRAUMA

Similar responses are seen in trauma, burns, sepsis and surgery.

Table 10. Distribution of Fat and Lean Mass

Fat Mass (25%) Lean Mass (75%)

Table 11. Terminology of Nutrition

Common Causes of Weight Loss

Table 12. Stress Factors Relative to Insult

Stress Stress Factors

BMR needs to be adjusted in the recovery phase as part of the weight

During stress 1.5 g/kg/day to 2 g/kg/day

iii). Providing Nutritional Support (nutrient mix):

ORGANIC COMPOUNDS FUNCTION

FLUID AND ELECTROLYTE BALANCE IN SURGERY.

Daily requirements for the average 70 Kg man;

Table 15. Crystalloids

Hartmans Normal Dextrose Ringers 5% Extracellular