Septic shock

Definition:
Septic shock may define as a generalized failure of tissue
perfusion resulting from infection and clinically manifest by
haemodynamic collapse and by metabolic evidence of impaired
blood flow
Phases of septic shock:
1. Early hyperdynamic phase (warm phase)
2. Late Hypodyanmic phase

Pathophysiology of septic shock

Septic shock results from endotoxaemia. Exposure of mammalian
cells to endotoxin results in cell injury in many ways –
1. Direct cell membrane damage by endotoxin
2. Extracellular relase of lysosomal enzymes from leucocytes
3. Activation of complement cascade
4. Metabolic injury due to tissue ishchemia

Aetiology
1. Surgical cause
a. Strangulated intestine
b. Peritonitis
c. After gas gangrene
d. Operation on large gut, genitourinary tract
e. Manipulation or instrumentation of urinary tract, GIT,
genital tract
f. Blood transfusion
2. Non-surgical cause
a. Pneumonia - lung
b. Endocarditis - heart
c. Meningitis – brain

Predisposing factors:
1. Very young or advanced age
2. Malnutrition
3. DM
4. Corticosteroid
5. Immunodeficency
6. Uraemia
7. Malignancy

Causative organism
1. E. coli
2. Klebsiella
3. Proteus
4. Pseudomonus aeruginosa
5. Bacteroids fragilis
6. Clostridium perferenges
Clinical feature
Hyperdynamic phase
1. Fever
2. Tachycardia
3. Hyperventilation
4. Warm extremities (dry,
pink)
5. Hypotension
6. Low peripheral resistence
7. Increased CVP
8. Increased cardiac index
hypotension unresponsive to adequate fluid replacement.
Hypodynamic pahse
1. Cyanosis
2. Vasoconstriction
3. Cold extremities
4. Marked hypotension
5. Decreased CVP
6. Decreased cardiac index
Failure of normal inhibitory mechanisms results in excessive
production of pro-inflammatory cytokines by macrophages, causing
hypotension, hypovolaemia, decreased perfusion and tissue
oedema.
In addition, uncontrolled neutrophil activation causes release of
proteases and oxygen free radicals within blood vessels, damaging
the vascular endothelium and further increasing capillary
permeability.
Direct activation of the coagulation pathway combines with
endothelial cell disruption to form clots within the damaged vessels.

The clinical consequences include cardiovascular collapse, acute

respiratory distress syndrome, disseminated intravascular
coagulation, multi-organ failure and often death.

Septic shock most frequently results from infection with Gram-

negative bacteria, because lipopolysaccharide is particularly
effective at activating the inflammatory cascade.

two of temperature > 38 °C or < 36 °C,

pulse rate > 90 beats per minute,
respiratory rate > 20 per minute or PCO2 < 4.3 kPa (32.5 mmHg),
and white blood cell count > 12 or < 4 × 109/L and
evidence of infection.
Septic shock describes sepsis plus hypotension
(systolic blood pressure < 90 mmHg systolic or a fall of > 40 mmHg
from baseline that is not responsive to fluid challenge or due to
another cause)

High output heart failure ---- Warm peripheries, pulmonary

congestion, blood pressure may be low, e.g. septic shock
In septic shock there may be a relative deficiency of vasopressin.

Endotoxin is a lipopolysaccharide (LPS) derived from the cell wall of

Gram-negative bacteria and is a potent trigger of the inflammatory
response
Release of pro- and anti-inflammatory mediators
Severe infection (often with bacteraemia or endotoxaemia), the
presence of large areas of damaged tissue (e.g. following trauma or
extensive surgery) or prolonged/repeated episodes of hypoperfusion
can trigger an exaggerated inflammatory response with systemic
activation of leucocytes and release of a variety of potentially
damaging ‘mediators’.
Although beneficial when targeted against local areas of infection or
necrotic tissue, dissemination of this ‘innate immune’ response can
produce shock and widespread tissue damage.

Characteristically the initial episode of overwhelming inflammation

is followed by a period of immune suppression, which in some cases
may be profound and during which the patient is at increased risk of
developing secondary infections.
It also seems that pro- and anti-inflammatory elements of the host
response may coexist.

Septic shock
Severe sepsis with hypotension (systolic BP < 90 mmHg or a
reduction of > 40 mmHg from baseline) in the absence of other
causes for hypotension and despite adequate fluid resuscitation
(Patients receiving inotropic or vasopressor agents may not be
hypotensive when perfusion abnormalities are documented)
Refractory shock
Shock unresponsive to conventional therapy (intravenous fluids and
inotropic/vasoactive agents) within 1 hour

In patients with septic shock, every effort must be made to identify

the source of infection and isolate the causative organism.
As well as a thorough history and clinical examination, X-rays,
ultrasonography or CT scanning may be required to locate the origin
of the infection.
Appropriate samples (urine, sputum, cerebrospinal fluid, pus drained
from abscesses) should be sent to the laboratory for microscopy,
culture and sensitivities.
Several blood cultures should be performed and empirical, broad-
spectrum antibiotic
therapy
Haemodynamic changes in shock should be
Septic shock
Low systemic vascular resistance
Low CVP and PAOP
Cardiac output usually high
Myocardial depression – low ejection fraction
Stroke volume maintained by ventricular dilatation
Cardiac output maintained or increased by tachycardia
commenced within the first hour of
recognition of sepsis.
If an organism is isolated later, therapy can be adjusted
appropriately.
The choice of antibiotic depends on the likely source of infection,
previous antibiotic therapy and known local resistance patterns, as
well as on whether infection was acquired in hospital or in the
community.
Abscesses must be drained and infected indwelling catheters
removed.

Whatever the aetiology of the haemodynamic abnormality, tissue

blood flow must be restored by achieving and maintaining an
adequate cardiac output, as well as ensuring that arterial blood
pressure is sufficient to maintain perfusion of vital organs.
Recently published guidelines for adult patients suffering severe
sepsis or septic shock advocate targeting an MAP > 65 mmHg, CVP
8–12 mmHg (>12 mmHg if mechanically ventilated), urine output
>0.5 mL/kg/h and an ScvO2 ≥ 70% (or SvO2 ≥ 65%) as the initial
goals of resuscitation.

Shock
Defination:
Shock may be defined as a widespread systemic
hypoperfusion due to reduced cardiac output or reduced circulatory
blood volume leading to hypotension followed by impair tissue
perfusion and cellular hypoxia.
Shock is the most common and most important cause of death of surgical
patients. Untreated, or inadequately treated, shock leads to organ damage and
ultimately death from multi-organ failure.

Pathophysiology of shock
A. Cellular

lactic acid.
carbon dioxide but
respiration is not
anaerobic
The product of
1. perfusion to the tissues is reduced, cells are deprived of
oxygen
- switch from aerobic to anaerobic metabolism
produce lactic acid
- accumulation of lactic acid in the blood produces a
systemic
metabolic acidosis.
2. Glucose within cells is exhausted, anaerobic respiration
ceases
- failure of sodium/potassium pumps in the cell
membrane and
intracellular organelles.
- Intracellular lysosomes release autodigestive enzymes
and cell lysis occurs. - Intracellular contents, including K+
released into the blood stream.
B. Microvascular
1. Progressive ischemia
- result in activation of the immune and coagulation
systems.
2. Hypoxia and acidosis
- activate complement and prime neutrophils,
- Resulting generation of oxygen free radicals and
release cytokine.
These mechanisms lead to
- injury of the capillary endothelial cells.
- in turn, further activate the immune and coagulation
systems.
Damaged endothelium loses its integrity and becomes ‘leaky’.
- Spaces between endothelial cells allow fluid to leak out
and
- tissue oedema ensues, exacerbating cellular hypoxia.
C. Systemic
1. Cardiovascular
- preload and afterload decrease
- a compensatory baroreceptor response
- resulting in increased sympathetic activity and
- release of catecholamines into the circulation.
This results in tachycardia and systemic vasoconstriction
(except in sepsis)
2. Respiratory
- The metabolic acidosis and increased sympathetic
response
- result in an increased respiratory rate and minute
ventilation
to increase the excretion of carbon dioxide
- (and so produce a compensatory respiratory alkalosis).
 3. Renal
 Decreased perfusion pressure in the kidney
- leads to reduced filtration at the glomerulus and
- a decreased urine output.
 The renin–angiotensin–aldosterone axis is stimulated
- resulting in further vasoconstriction and
- increased sodium and water reabsorption by the
kidney.
4. Endocrine
 Activation of the adrenal and renin–angiotensin systems
a) Vasopressin (antidiuretic hormone) is released from
the hypothalamus
- in response to decreased preload
- results in vasoconstriction and resorption of
water
b) Cortisol is also released from the adrenal cortex
- contributing to the sodium and water resorption
and
- sensitizing the cells to catecholamines.
D. Ischaemia–reperfusion syndrome
 Once normal circulation is restored to those hypoxic
tissues further injury occurs
 The acid and potassium load that has built up can lead
to
- direct myocardial depression,
- vascular dilatation and
- further hypotension.
 The cellular and humoral elements activated by the
hypoxia (complement,
neutrophils, microvascular thrombi) are flushed back into the
circulation
- There they cause further endothelial injury to organs
such as the lungs
and the kidneys. This leads to
- acute lung injury,
- acute renal injury,
- multiple organ failure and
- death.
Reperfusion injury can currently only be attenuated by reducing the
extent and duration of tissue hypoperfusion.
 Types of Shock
There are five main types of shock that can be grouped into two
pathogenic groups:
1. Vasoconstrictive / Low flow shock:
a. Hypovolaemic shock
Haemorrhagic cause – blood loss
Diarrohea – fluid
loss Vomiting –

Non haemorrhagic cause – fluid loss (Diarrohea,

Burn – plasma
loss trauma –

vomiting, burn, trauma)

blood loss
fluid loss

 Obsrtuctive shock mimics hypovolaemic shock

Tension pneumothorax,
Cardiac temponade,
Massive pulmonary embolosm
b. Cardiogenic shock
MI, ventricular rupture,
arrhythmia, cardiac temponade,
pul. embolism
2. Vasodilative/ Distributive:
c. Septic –
Overwhelming microbial infection,
endotoxic shock,
Gm+ve septicemia,
Fungal sepsis,
Superantigen
d. Neurogenic –
Anaesthetic accident, spinal injury
e. Anaphylactic shock –
Ig E mediated hepersensetivity
[f. Endocrine shock – Baily & love]
Hyper/Hypo thyroidism,
Adrenal insufficiency

Hypovolaemic shock:
Hypovolaemic shock results from a loss of volume within the
circulation.
it may be due to whole blood loss from haemorrhage, or plasma and
fluid loss from burns or severe medical conditions.
Compensatory mechanism can maintain systolic BP up to around a) 30 %
Constriction of
blood loss in a fit patient. small vein & venules
> 30 % blood loss compensation increasingly fails until unconsciousness,
of whole body
at around 50 % blood loss followed by death. ↓
↑Venous return
Early compensatory mechanisms are ↓
Tachycardia and ↑EDV
Peripheral vasoconstriction with a narrowed pulse pressure ↓
↑CO e.g.
[vasoconstriction ↑diastolic BP bringing it closer to the systolic,
b) Selective
120/60 →120/90] constriction of the
Further compensations include arterioles of
tachypnoea, skin,skeletal muscle,
shift of fluid from tissues into circulation and spleen, gut
reduced urine output. ↓
Diversion of blood to
organs that withstand
Pathophysiology of hypovolumic shock ischemia (Brain, heart)
c) Reabsorption of
A. Reversible shock/ compensated stage: water, electrolyte by
Hmg, Vomiting, Diarrohea, burn Renin-angiotensin –
↓
Acute hypovolaemia → Collapse of venules & small veins
↓
↓ CVP
↓
↓ EDV (End diastolic volume)
↓
↓ CO (cardiac output) (+) baroreceptor
↓  Discharge of CVS
↓ BP adrenergic
 Release of vasopressin &
↓
Reversible shock (Compensatory autoregulation - ↑ BP)

B. Irreversible shock/ decompensated stage:

Hmg, Vomiting, Diarrohea, burn
↓
Severe hypovolaemia
↓ If not corrected
Compensatory mechanism failure
↓
Hypoperfusion of tissue
↓
Acute Hypoxia
↓
1. Endothelial injury leads to activation of coagulation
cascade DIC
2. Anaerobic glycolysis → Lactic acid → ↓ PH → Vasodilation
→ ↓ BP
↓
Severe hypoxia
 ↓
Damage to cell & tissue
↓
ATN (Reanal)
↓
Complete renal shut down
↓
Death

Clinical presentation:

Investigation
1. CBC 5. Blood for grouping & cross
matching
2. ABG analysis 6. RBS
3. Renal function 7. Blood for C/S
a. Blood urea 8. X-ray, USG, CT – source of
bleeding
b. S. creatinine 9. S. Electrolyte
4. Liver function 10. ECG
a. SGPT,PT
b. S. billirubin
Management
1. Assessment of the patient condition
2. An immediate step is to put in at least two large bore I/V
canulas (No. 16 or 14).
3. Maintenance of respiration
a. Airway clearance by sucction
b. Maintain patent airway by – O2 inhalation, IPPV, Lt.
lateral position , neck extended
4. Maintenance of circulation
a. I/V fluid
b. Plasma expandature
c. Blood
5. Prevention of renal failure
a. Catheterization
b. Keep urine output 50ml/hr
c. Diuretics if required
6. Correction of acidosis and electrolyte
imbalance
a. 7.5 sodium bicarbonate
solution
7. Treatment of underlying cause
8. Continuous monitoring
From Ganong – Shock
Def: Inadequate tissue perfusion with a relatively or absolutely inadequate
cardiac output.
 Inadequate cardiac output –
Absolute - amount of fluid in the vascular system is inadequate to fill it
(hypovolemic shock).
Relative - the size of the vascular system is increased by vasodilation even
though the blood
volume is normal (distributive, vasogenic, or low-resistance
shock).
 Inadequate pumping action of the heart as a result of myocardial
abnormalities (cardiogenic shock),
 Inadequate cardiac output due to obstruction of blood flow in the lungs or
heart (obstructive shock).
Hypovolemic shock is also called "cold shock." It is characterized by
 Hypotension;
 A rapid, thready pulse;
 Cold, pale, clammy skin;
 Intense thirst;
 Rapid respiration; and
 Restlessness or, alternatively, torpor.
None of these findings, however, are invariably present.
Multiple compensatory reactions that come into play to defend
extracellular fluid (ECF) volume.
 The decline in blood volume produced by
- Bleeding decreases venous return, and cardiac output falls.
- The heart rate is increased, and with severe hemorrhage, a fall in blood
pressure always occurs.
 With moderate hemorrhage (5–15 mL/kg body weight),
- Pulse pressure is reduced but mean arterial pressure may be normal.
- The blood pressure changes vary from individual to individual, even when
exactly the same
amount of blood is lost.
 The skin is cool and pale and may have a grayish tinge because of stasis in
the capillaries and a small amount of cyanosis.
 Inadequate perfusion of the tissues leads to increased anaerobic
glycolysis, with the production of large amounts of lactic acid.
- In severe cases, blood lactate level rises from about1 mmol/L(normal) to
9 mmol/L or more.
- The resulting lactic acidosis depresses
a) the myocardium,
b) decreases peripheral vascular responsiveness to
catecholamines, and
c) may be severe enough to cause coma.
 When blood volume is reduced and venous return is
decreased,
- stimulation of arterial baroreceptors is reduced, increasing sympathetic
output.
- Even if there is no drop in mean arterial pressure, the decrease in pulse
pressure decreases the rate of discharge in the arterial baroreceptors, and
reflex tachycardia and vasoconstriction result.
 With more severe blood loss
 - tachycardia is replaced by bradycardia; this occurs while shock is still
reversible.
- With even greater hemorrhage, the heart rate rises again.
[The bradycardia is presumably due to unmasking a vagally mediated
depressor reflex, and the response may have evolved as a mechanism for
stopping further blood loss.]
 Vasoconstriction is generalized, sparing only the vessels of the brain and
heart.
- A widespread reflex venoconstriction also helps maintain the filling
pressure of the heart.
 In the kidneys
- Both afferent and efferent arterioles are constricted,
but the efferent vessels are constricted to a greater degree.
- The glomerular filtration rate is depressed,
but renal plasma flow is decreased to a greater extent,
- So that the filtration fraction increases.
 Na+ retention is marked, and
 The nitrogenous products of metabolism are retained in the blood
(azotemia or uremia).
 If the hypotension is prolonged,
- renal tubular damage may be severe (acute renal failure).

After a moderate hemorrhage, the circulating plasma volume is restored in 12 to

72 h.
Preformed albumin also enters rapidly from extravascular stores,
but most of the tissue fluids that are mobilized are protein-free.
After the initial influx of preformed albumin, the rest of the plasma protein
losses are replaced, presumably by hepatic synthesis, over a period of 3 to
4 d.
Erythropoietin appears in the circulation, and the reticulocyte count increases,
reaching a peak in 10 d.
The red cell mass is restored to normal in 4 to 8 wk.

Shock is more profound in patients with elevated temperatures because of

cutaneous vasodilation, and patients in shock should not be warmed to the point
that their body temperature rises.

The hyperventilation in shock is due to chemoreceptor stimulation

caused by acidosis and hypoxia secondary to local stagnation of blood flow,
and is not baroreceptor-mediated.
The activity of inspiratory neurons affects blood pressure and heart rate, and
activity in the vasomotor and cardiac areas in the medulla may have minor effects
on respiration.

Davidson
‘Shock’ is a level of oxygen delivery (DO2) which fails to meet the metabolic
requirements of the tissues.
The causes of circulatory failure or ‘shock’ may be categorized as either low flow
(reduced stroke volume)
or low peripheral arteriolar resistance (vasodilatation

A. Low stroke volume

i. Hypovolaemic: any condition provoking a major reduction in blood
volume, e.g. internal or external haemorrhage, severe burns, salt and
water depletion.
ii. Cardiogenic: severe mechanical impairment, e.g. myocardial infarction,
acute mitral regurgitation.
iii. Obstructive: obstruction to blood flow around the circulation, e.g. major
pulmonary embolism, cardiac tamponade, tension pneumothorax.
B. Vasodilatation
i. Septic/SIRS: infection or other causes of a systemic
inflammatory response that produce widespread endothelial damage with
vasodilatation, arteriovenous shunting, microvascular occlusion, capillary
leak and tissue oedema.
ii. Anaphylactic: inappropriate vasodilatation triggered by an
allergen (e.g. bee sting), often associated with endothelial disruption and
capillary leak.
iii. Neurogenic: caused by major brain or spinal injury which
disrupts brain-stem and neurogenic vasomotor control.

 Raised diastolic (DBP) and reduced systolic (SBP) such as 105/95

mmHg, indicates the combinationof hypovolaemia (reduced stroke volume,
hence SBP) and
 activation of the sympathetic nervous system, with noradrenaline
(norepinephrine)-induced vasoconstriction raising the DBP.

Hypovolaemic, cardiogenic and septic shock and anaphylactic

obstructive
 Cold peripheries
 reduced or absent peripheral
pulses, weak
 central pulses / (thready pulse)
 evidence of a low cardiac output
 early haemorrhagic shock,
a narrowed pulse pressure, i.e. a
raised diastolic (DBP) and reduced
systolic (SBP) such as 105/95 mmHg,
indicates the combination of
hypovolaemia (reduced stroke volume,
hence SBP) and activation of the
sympathetic nervous system, with
noradrenaline (norepinephrine)-induced
vasoconstriction raising the DBP.
shock
 warm peripheries
 Bounding pulses
 and features of a high cardiac
output
 early stages,
- peripheral vasodilatation results in
a low DBP,
- but since the left ventricular
afterload is reduced, stroke volume and
hence systolic BP are maintained, e.g.
115/42 mmHg
 in more advanced case
- SBP falls and the peripheries
become cool - due to the hypovolaemia
associated with capillary leak and will
respond to fluid resuscitation.
- If it does not, it is possible that
myocardial depression is present.