Sepsis

Septic shock

Hamed Rashad
 Septic Shock
• Septic shock- once a uniformly fatal
condition with 100% mortality.

• Present recovery rates are more than 50%.

Mortality from Sepsis Martin NEJM 2003
 Reference Diseases

• Incidence in US (cases per 100,000)

– AIDS1 17
– Colon and rectal cancer2 48
– Breast cancer2 112
– Congestive heart failure3 ~196
– Severe sepsis4 ~300
• Number of deaths in US each year
– Acute myocardial infarction5 218,000
– Severe sepsis4 215,000
1
Centers for Disease Control and Prevention. 2000. Incidence rate for 1999.
2
American Cancer Society. 2001. Incidence rate for 1993-1997.
4
Angus DC et al. 2001. Crit Care Med 29:1303-1310.
5
National Center for Health Statistics. 2001.
 Sepsis on the Rise
• Incidence projected to rise during the next decade
– Aging population especially in developed nations
– Increased awareness and diagnosis
– Immunocompromised patients e.g. cancer therapy,
transplantation)
– Invasive procedures (ventilators, catheters, prostheses)
– Resistant pathogens

Angus DC et al. 2001. Crit Care Med 29:1303-1310.

Balk RA. 2000. Crit Care Clin 16(2):179-191
 Definitions

SIRS Sepsis Severe Septic

Infection Sepsis Shock
 Systemic Inflammatory
Response Syndrome
• Systemic Inflammatory Response Syndrome
(SIRS)--the beginning of illness
  2 of the following:
• Temp > 38C or < 36C
• Heart rate > 90 pm
• Respiratory rate > 20 pm
• WBC > 12,000, < 4,000 or bands > 10%
Bone, et al. 1992. Chest 101:1644-1655
 Sepsis
• Sepsis
– SIRS + infection
• Severe sepsis
– Sepsis with organ dysfunction, hypoperfusion or
hypotension
• Septic Shock
– Sepsis with hypotension and perfusion abnormalities
despite adequate volume replacement

Bone, et al. 1992. Chest 101:1644-1655

 Definition
Infection/ Sepsis Severe Sepsis
Trauma SIRS

Sepsis with ≥1 sign of organ failure

 Cardiovascular (refractory
hypotension)
 Renal
 Respiratory
 Hepatic Shock
Bone et al. Chest. 1992;101:1644;  Hematologic
Wheeler and Bernard. N Engl J Med.  CNS
1999;340:207.
 Unexplained metabolic acidosis
 Multiple Organ Dysfunction
Syndrome (MODS/MOF)
MODS/MOF = the presence of altered organ
function in an acutely ill patient such that
homeostasis cannot be maintained without
intervention.
 Primary MODS = a well-defined insult, occurs early and
can be directly attributable to the insult itself (eg, renal
failure due to rhabdomyolysis).
 Secondary MODS = not in direct response to the insult
itself, but as a consequence of a host response. MODS
represents the more severe end of severity of illness
characterized by SIRS/sepsis.

Crit Care Med 1992; 20:864

 Identifying Acute Organ
Dysfunction as a Marker of
Altered
Consciousn
Severe Sepsis Tachycardia
ess Hypotensio
Confusion n
Psychosis  CVP
 PAOP
Tachypnea
PaO2 <70 mm Oliguria
Hg Anuria
SaO2 <90%  Creatinine
PaO2/FiO2 300

 Platelets
Jaundice  PT/APTT
 Enzymes  Protein C
 Albumin  D-dimer
 PT
 Septic Shock
Septic shock = sepsis induced 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.
– Hypotension = systolic BP of <90 mmHg or a reduction
of ≧40 mmHg from baseline in the absence of other
causes for the fall in blood pressure.

Crit Care Med 1992; 20:864

 Septic shock :Causes

--Common sites of infection in decreasing order :

the chest, the abdomen, and the genitourinary
tract.

– 70% due to gram-negative bacteria

(Enterobacteriaceae, P aeruginosa)
– 30% are caused by gram-positive bacteria
(Strept pneumoniae, Staph aureus, Enterococ
species).
 Primary Sites of Infection in a recent large
study of Septic shock
60 Drotrecogin Alfa
(activated) N=850
50
Percent of Patients

Placebo N=840
40

30

20

10

0
Lung Intra- Urinary Blood Skin Other
Abdominal Tract

Site of Infection
Changes in the Documented Causes of Sepsis
Martin NEJM 2003
Why do people die from Sepsis?
• Very few organisms produce toxins that cause
death directly
– Diptheria
– Tetanus, botulism
– Pseudomonas aeruginosa ?

• Death from sepsis is mainly due to

inflammation
 Pathogenesis of Sepsis
• A wide variety of microorganisms cause sepsis
• How--there must be some common mechanism

• Interaction of specific Pathogen Associated Molecular

Patterns (PAMPs)with Toll-like receptors (Tlrs) on
the macrophage stimulate production of inflammatory
mediators
 Innate Immune response Sepsis
• Interaction of a microbial signature with a toll-like receptor leads to activation of
innate immune mechanism
– Antimicrobial peptide (DEFENSINS) synthesis and release which can kill
most organisms
– Release of Mediators of inflammation - cytokines, chemokines

– PMN leucocytes come into the site of inflammation to

phagocytize organisms--release enzymes

– Normally protective but either overwhelmed by bacterial

inocula or some type of dysregulation leads to severe SEPSIS
Synthesis and release of Effector molecules
leading to the SEPSIS syndrome and shock
Crit Care Med 2000 28(4):N3-N12
 Incomplete Rx
Corticosteroid or relapse ???

High viral load Good side

remove virus

Cytokine Storm ?

Bad side
Genetic predisposition ARDS
to immune hyperstimulation MODS
 Pathophysiology
• What ‘type of shock’ is septic shock?
Septic shock has features of :
– Hypovolemic shock
– Cardiac shock
– Distributive shock.
Pathophysiology of septic shock
and SIRS
• The hemodynamic derangements observed
in septic shock and SIRS are due to a
complicated cascade of inflammatory
mediators released in response to infection,
inflammation, or tissue injury.
 Pathophysiology of septic shock
and SIRS
• Tumor necrosis factor-alpha (TNF-alpha),
interleukin (IL)-1b, and IL-6 act
synergistically with other cytokines and
phospholipid-derived mediators to produce
the complex alterations in vascular and
myocardial function, which leads to
maldistribution of blood flow
 Pathophysiology:
• Decreased tissue perfusion results primarily
from :
• 1-arterial hypotension due to reduction in
SVR.
• 2-reduction in effective circulating plasma
volume due to: a-- decrease in venous tone
and subsequent pooling of blood in venous
capacitance vessels.
 Pathophysiology:
b-loss of intravascular volume into the interstitium
due to increased capillary permeability also
occurs.
• Finally, primary myocardial dysfunction often is
present as manifested by ventricular dilatation,
decreased ejection fraction (despite normal stroke
volume and cardiac output), and depressed
ventricular function curves
 Pathogenesis of Severe Sepsis
Infection

Microbial Products
(exotoxin/endotoxin)

Cellular Responses

Platelet Coagulation Kinins Cytokines

Activation Activation Oxidases Complement TNF, IL-1, IL-6

Coagulopathy/DIC
Vascular/Organ System Injury

Endothelial d he lia l d amage

amage Endot
Multi-Organ Failure

Death
Severe Sepsis: The Final Common Pathway
Cytokine storm
Endothelial Dysfunction and
Microvascular Thrombosis

Hypoperfusion/Ischemia

Acute Organ Dysfunction

(Severe Sepsis)

Death
Clinical Manifestations.
• The Continuum of infection
to
MODS and Death
(Clinical Definition)
 History:

* Dyspnea or respiratory distress, mental status

changes, and obtundation.

* Prior complaints suggesting infection or

inflammation of the respiratory tract, urinary tract, or
abdominal cavity.

* Septic shock occurs frequently in hospitalized

patients with risk factors, such as indwelling
catheters or venous access devices, recent surgery, or
immunosuppressive therapy.
 Physical examination:

– Hypotension - With systolic blood pressure less than 90 mm

Hg or a reduction of 40 mm Hg from baseline
– Fever

– Heart rate - Greater than 90

– Respiratory rate - Greater than 20

– Extremities - Frequently are warm - bounding pulses and

increased pulse pressure .
 Septic Shock Is Unique
• Cardiac output may be normal, increased,
or decreased.
• Hypotension and poor end-organ perfusion may be
present despite “good” skin perfusion. Hypotension
is still a sign of decompensation.
• Early signs of sepsis/septic shock include
— Fever or hypothermia
— Tachycardia and tachypnea
— Leukocytosis, leukopenia, or increased bands
Septic Shock: “Warm Shock”

• Early, compensated, hyperdynamic state

• Clinical signs
– Warm extremities with bounding pulses, tachycardia,
tachypnea, confusion.
• Physiologic parameters
– widened pulse pressure, increased cardiac output and mixed
venous saturation, decreased systemic vascular resistance.
• Biochemical evidence:
– Hypocarbia, elevated lactate, hyperglycemia
 Septic Shock: “Cold Shock”
• Late, uncompensated stage with drop in cardiac output.
• Clinical signs
– Cyanosis, cold and clammy skin, rapid, thready pulses,
shallow respirations.
• Physiologic parameters
– Decreased mixed venous sats, cardiac output and CVP,
increased SVR, thrombocytopenia, oliguria, myocardial
dysfunction, capillary leak
• Biochemical abnormalities
– Metabolic acidosis, hypoxia, coagulopathy, hypoglycemia.
 Septic Shock (con’t)
 Cold Shock rapidly progresses to MOSF or
death, if untreated

 Multi-Organ System Failure: Coma, ARDS,

CHF, Renal Failure, Ileus, hemorrhage,
DIC

 More organ systems involved, worse the

prognosis
 Clinical Manifestations.
Recognition of Septic Shock:
• Inflammatory triad-
– Fever
– Tachycardia
– flushed skin Warm
Shock
• Hypoperfusion
– Altered sensorium
– Urine output
– >CFT
– Wide pulse pressure.......bounding pulses
 Clinical Manifestations.
• Hypotension
– Cold and clammy skin
– Mottling
– Tachycardia Cold shock
– Cyanosis
– Narrow pulse pressure
– Hypoxemia
– Acidosis.
 Clinical Manifestations.
Staging of Septic Shock:
I. Compensated / Preshock / Hyperdynamic

II.Decompensated / Organ hypoperfusion

III. End organ failure / Irreversible

 Lab Studies:

• All patients with evidence of shock should have the

following studies performed:
– CBC with differential
– Arterial blood gas
– Serum lactate if metabolic acidosis or elevated anion gap is present
– Electrolytes
– BUN
– Creatinine (CR)
– Glucose
– Urinalysis
– Blood cultures
– Urine cultures
 Imaging Studies:
• All patients should have a chest x-ray.

• Flat and upright abdominal radiographs may be omitted if the

abdomen is completely benign or if an obvious source of
extraabdominal sepsis noted.

• In suspected cases of cholecystitis or pancreatitis, abdominal

ultrasound is most useful to assess for cholelithiasis, biliary
dilatation, and fluid collections around the gallbladder or the
head of the pancreas.

• Consider abdominal CT scan with oral and/or intravenous

contrast for other abdominal sources for sepsis
 Other Tests:
• ECG should be performed to examine for
evidence of underlying cardiac pathology
(left ventricular hypertrophy, cor
pulmonale, low voltage, bundle branch
block) or acute changes of ischemia or
pericarditis
 Management
Prevention:
1. Immunisation

2. Prompt treatment of local infections

3. Hospitalized patient: look out for nidus

of infection- IV lines, catheters, E.tubes
 Management
Recognise septic shock early:
• Remember- Inflammatory triad
Signs of hypoperfusion

• Do not wait for the BP to fall !

• Lower limit for systolic BP in children = 70 +

( age x 2)
 Management.
• Two means of death:
1. Shock.
2. Multi organ failure.
• Aims of treatment:
1. Assure perfusion of critical vascular
beds. ( cerebral, coronary, renal)
2. Rx underlying cause.
Guidelines for Management of Severe Sepsis and Septic
Shock
• I. MANAGEMENT OF • II. SUPPORTIVE THERAPY
SEVERE SEPSIS OF SEVERE SEPSIS
– Initial Resuscitation – Mechanical Ventilation of
– Diagnosis Sepsis-induced ALI/ARDS
– Antibiotics Therapy – Sedation, Analgesia, and N-M
– Blockade in Sepsis
Source Control
– – Glucose Control
Fluid therapy
– – Renal Replacement
Vasopressors
– – Bicarbonate Therapy
Inotropic Therapy
– DVT Prophylaxis
– Corticosteroid
– – Stress Ulcer Prophylaxis
Recombinant Human Activated
Protein C (rhAPC) – Selective Digestive Tract
– Blood Product Administration Decontamination (SDD)
– Consideration for Limitation of
Support
• III. Pediatric Consideration
 Most Effective therapies
• Early recognition of preshock- tachypnea
leading to respiratory alkalosis
– Low Pco2, pH >7.45
• Lots of intravenous Fluids
• Antibiotics
• Effective antibiotics
• Timely administration of Effective
antibiotics
 Treatment
• Nearly all patients with shock should be
admitted to an ICU.
• Vital signs and fluid intake and output
should be measured and charted on an
hourly basis.
• Adequate intravenous access should be
obtained.
 Treatment

• A central venous access device should be

considered if vasoactive drug support is required.
• Most patients should have an indwelling urinary
catheter placed.
• All patients should be treated prophylactically
against thromboembolic disease, gastric stress
ulceration, and pressure ulcers of the skin.
 Goals of treatment
• The 2 primary goals are to :
• 1- reverse the initiating cause of shock
(e.g.treat infection)
• 2- stabilize the patient hemodynamical.

• The initial resuscitation should be

accomplished within the first hour of treatment.
 Treatment
• Oxygen by mask.

• In patients with altered mental

status,respiratory distress, or severe
hypotension, elective endotracheal
intubation and mechanical ventilation
should be considered strongly.
 Treatment
• In all patients with sepsis, Empiric antibiotic
therapy should be initiated immediately

• Antimicrobial coverage should be Broad

 Initial Resuscitation

Figure B, page 948, reproduced with permission from Dellinger RP. Cardiovascular
management of septic shock. Crit Care Med 2003;31:946-955.
EGDT first 6
hours in ER
500ml bolus of
colloid every 30min
Dobutamin started at
2.5 ug/kg/min,
increase by
2.5ug/kg/min every
30 min, or until
maximal dose
20ug/kg/min given

Decrease
dobutamin dose
if MAP
>65mmHg or
HR> 120bpm
 Initial Resuscitation (2008)
Initial resuscitation (first 6 hrs)
 Begin resuscitation immediately in patients with hypotension or elevated
serum lactate 4 mmol/L; do not delay pending ICU admission (1C)
Resuscitation goals (1C)
CVP 8–12 mm Hg a
Mean arterial pressure 65 mm Hg
Urine output 0.5 mL/kg/hr
Central venous (superior vena cava) oxygen saturation 70% or mixed
venous 65%
If venous oxygen saturation target is not achieved (2C)
Consider further fluid
Transfuse packed red blood cells if required to hematocrit of 30%
and/or
Start dobutamine infusion, maximum 20 μg/kg/min
 Diagnosis
• Obtain appropriate cultures before starting antibiotics provided this
does not significantly delay antimicrobial administration (1C)
– Obtain two or more BCs
– One or more BCs should be percutaneous
– One BC from each vascular access device in place 48 hrs
– Culture other sites as clinically indicated
• Perform imaging studies promptly to confirm and sample any
source of infection, if safe to do so (1C), (ex. Sonography suitable,
transport outside unit may be dangerous)
 Antibiotic Therapy (2008)
• Begin intravenous antibiotics as early as possible and
always within the first hour of recognizing severe
sepsis (1D) and septic shock (1B)
– In the presence of septic shock, each hour delay in
achieving administration of effective antibiotics is
associated with a measurable increase in mortality
• Broad-spectrum: one or more agents active against
likely bacterial/fungal pathogens and with good
penetration into presumed source (1B)
– Watch out MRSA in some communities and healthcare
settings
 Antibiotic Therapy (2008)
• Reassess antimicrobial regimen daily to
optimize efficacy, prevent resistance,
avoid toxicity, and minimize costs (1C)
• Consider combination therapy in
Pseudomonas infections (2D)
• Consider combination empiric therapy
in neutropenic patients (2D)
 Antibiotic Therapy (2008)
• Combination therapy 3–5 days and de-
escalation following susceptibilities (To
single therapy) (2D)
• Duration of therapy typically limited to 7–10
days; longer if response is slow or there are
undrainable foci of infection or immunologic
deficiencies (1D)
• Stop antimicrobial therapy if cause is found
to be noninfectious (1D)
 Optimum therapy of Sepsis and Shock
• Antibiotics remain the most critical choice to be made
– TIMELY-reduces mortality
– EFFECTIVE, BROAD SPECTRUM-reduces mortality
– DIFFERENT antibiotics for different patients
– P. aeruginosa continues to be associated with highest mortality
– Resistance issues need to be kept in mind
– A large number of patients with the sepsis syndrome will not have an
organism cultured but should be treated with antibiotics
• Prevent the development of septic shock - fluids and
Right antibiotics
 Antibiotic Choices
• Given the world wide resistance issues the most effective
antibiotic choices to cover gram negatives would be
– Fourth generation cephalosporins ± aminoglycoside
(Geographic location)
– Carbapenems ± aminoglycoside (Pseudomonas
resistance during therapy of Lung infections)
– Pip-Tazobactam + an aminoglycoside (Esbl
resistance)
• If the incidence of MRSA is high and gram positive
coverage is needed, add an anti Staphylococcal agent
--Vanco, Teicoplanin
 Choosing the RIGHT antibiotic in Sepsis

• Site of Infection, if known it helps to limit choices

– intraabdominal, or necrotizing soft tissue infection needs anaerobic
coverage.
– Skin infections require gram positive coverage
• Lung most common site of documented infection-P. aeruginosa, S.
aureus,
• Know resistance picture in hospital
– ESBLs, P. aeruginosa, choose best drugs against these
• Know resistance in community if sepsis is community acquired - S.
aureus, S. pneumoniae, E.coli
• Give the antibiotic as soon as possible
 Non antibiotic therapy of septic shock

2002 opinion
 Source identification and control
(2008)
• A specific anatomic site of infection should be
established as rapidly as possible (1C) and within
first 6 hrs of presentation (1D)
– E.g., necrotizing fascitis, diffuse peritonitis, cholangitis,
intestinal infarction)
• Formally evaluate patient for a focus of infection
amenable to source control measures (e.g. abscess
drainage, tissue debridement, removal of a potentially
infected device, or the definitive control of a source
of ongoing microbial contamination) (1C)
 Source identification and control
(2008)
• Implement source control measures as soon as
possible following successful initial resuscitation
(1C) (exception: infected pancreatic necrosis, where
surgical intervention is best delayed) (2B)
• Choose source control measure with maximum
efficacy and minimal physiologic upset (1D)
– e.g., percutaneous rather than surgical drainage of an
abscess
• Remove intravascular access devices if potentially
infected (1C)
– Prompt remove after other vascular access had been
established
 :
Fluid Therapy (2008)

• Fluid resuscitation may consist of natural or artificial

colloids or crystalloids (1B)
 Fluid Therapy (2008)
• Resuscitation initially target a central venous pressure
of 8 mm Hg (12 mm Hg in mechanically ventilated
patients) (1C)
• A fluid challenge technique be applied wherein fluid
administration is continued as long as the
hemodynamic improvement (e.g., arterial pressure,
heart rate, urine output) continues (1D)
 Fluid Therapy (2008)
• The rate of fluid administration be reduced when ：
cardiac filling pressures (central venous pressure or
pulmonary artery balloon-occluded pressure)
increase without concurrent hemodynamic
improvement
• (1D)
 Vasopressors (2008)
• Mean arterial pressure (MAP) be maintained 65 mm Hg (≧
65) (1C)
– Sustain life and maintain perfusion in the face of life-threatening
hypotension
• Either NOREPI or DOPA administered through a central
catheter is the initial vasopressor of choice (1C)
• Epinephrine, phenylephrine, or vasopressin should not be
administered as the initial vasopressor in septic shock (2C).
Vasopressin 0.03 units/min may be subsequently added to
norepinephrine with anticipation of an effect equivalent to
norepinephrine alone
 Vasopressors (2008)
• Epinephrine be the first chosen alternative agent in
septic shock that is poorly responsive to
norepinephrine or dopamine (2B)
• Do not use low-dose dopamine for renal perfusion
(1A)
– Bellomo et al. Lancet 2000
• In patients requiring vasopressors, place an
arterial catheter as soon as possible.(1D)
 Corticosteroid (2008)
• Consider intravenous hydrocortisone for adult
septic shock when hypotension responds poorly to
adequate fluid resuscitation and vasopressors (2C)
• ACTH stimulation test is not recommended to
identify the subset of adults with septic shock who
should receive hydrocortisone (2B)
• Hydrocortisone is preferred to dexamethasone
(2B)
 Corticosteroid (2008)
• Fludrocortisone (50 g orally once a day) may be
included if an alternative to hydrocortisone is
being used that lacks significant mineralocorticoid
activity. Fludrocortisone if optional if
hydrocortisone is used (2C)
• Steroid therapy may be weaned once vasopressors
are no longer required (2D)
• Hydrocortisone dose should be 300 mg/day (1A)
• Do not use corticosteroids to treat sepsis in the
absence of shock unless the patient’s endocrine or
corticosteroid history warrants it (1D)
 Steroid Therapy

Figure 2A, page 867, reproduced with permission from Annane D, S ébille V, Charpentier C, et
al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in
patients with septic shock. JAMA 2002; 288:862-871
 Human Activated Protein C
Endogenous Regulator of Coagulation

Protein Protein C Activity

C (Inactive)
Protein
S
Blood Vessel
Blood Flow 
Thrombin Protein C
Receptor
Thrombomodulin
Human Activated Protein C in Septic
Shock
• Activated protein C had anti-thrombotic,
anti-inflammatory and pro-fibrinolytic
properties
– Drotrecogin Alfa is the first anti-inflammatory
agent that proved effective in the treatment of
sepsis
From Recombinant human activated
protein c worldwide evaluation in severe
sepsis (PROWESS) study group
Bernard et al. NEJM, 2001
 Results: 28-Day All-Cause Mortality
Primary analysis
results
2-sided p-value 0.005
Adjusted relative risk reduction
35
19.4%
Increase in30.8%
odds of survival 38.1%
30 6.1%
24.7% absolute
Mortality (%)

25
reduction
20
in mortality
15 Placebo Drotrecog
10 in alfa
(n-840)
(activated
5
) (n=850)
0
Adapted from Table 4, page 704, with permission from Bernard GR, Vincent JL, Laterre PF, et al.
Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med
2001; 344:699-709
 Mortality and APACHE II Quartile

118:80
50
Placebo
45
Mortality (percent)

40 Drotrecogin
35
58:48
30
57:49
25
20
15
26:33
10
5
0
1st (3-19) 2nd (20-24) 3rd (25-29) 4th (30-53)
APACHE II Quartile
*Numbers above bars indicate total
Adapted from Figure 2, page S90, with permission from Bernard GR. Drotrecogin alfa (activated)
(recombinant human activated protein C) fordeaths
the treatment of severe sepsis. Crit Care Med 2003;
31[Suppl.]:S85-S90
 Mortality and Numbers of Organs Failing

60
50
Percent
Mortality
40
30
20
Placebo 10
Drotrecogin
0
1 2 3 4 5
Number of Organs Failing at Entry
Adapted from Figure 4, page S91, with permission from Bernard GR. Drotrecogin alfa (activated)
(recombinant human activated protein C) for the treatment of severe sepsis. Crit Care Med 2003;
31[Suppl.]:S85-S90
 Blood Product Administration
(2008) Red Blood Cells

• Give red blood cells when hemoglobin

decreases to 7.0 g/dL (70 g/L) to target a
hemoglobin of 7.0–9.0 g/dL in adults (1B).
• A higher hemoglobin level may be required in
special circumstances (e.g., myocardial ischaemia,
severe hypoxemia, acute hemorrhage, cyanotic heart
disease, or lactic acidosis)
 Blood Product Administration (2008)

• Do not use erythropoietin to treat sepsis-related anemia.

Erythropoietin may be used for other accepted reasons
(chronic renal failure). (1B)
• Do not use fresh frozen plasma to correct laboratory
clotting abnormalities unless there is bleeding or
planned invasive procedures (2D)
• Do not use antithrombin therapy (1B)
 Blood Product Administration (2008)

• Administer platelets when (2D)

– Counts are 5000/mm3 (5x 109/L) regardless of bleeding
– Counts are 5000–30,000/mm3 (5–30x109/L) and there is
significant bleeding risk
• Higher platelet counts (50,000/mm3 [50x 109/L]) are
required for surgery or invasive procedures
Mechanical Ventilation of Sepsis-
Induced ALI/ARDS (2008)
 Mechanical Ventilation of
Sepsis-Induced ALI/ARDS
• Target a tidal volume of 6 mL/kg (predicted) body
weight in patients with ALI/ARDS (1B)
• Target an initial upper limit plateau pressure 30 cm
H2O. Consider chest wall compliance when
assessing plateau pressure (1C)
– If plateau pressure remain > 30 after reduction of
tidal volume to 6 ml/kg PBW, tidal volume should
be reduced further to as low as 4 ml/kg
 Mechanical vent
• Allow PaCO2 to increase above normal, if needed, to
minimize plateau pressures and tidal volumes (1C)
– Permissive hypercapnia
– Be limited in patients with preexisting metabolic acidosis and
contraindicated in patients with increased initracranial pressure.
• Set PEEP to avoid extensive lung collapse at end-expiration
(1C)
– Titrate PEEP based on
1. Bedside measurement of thoracopulmonary compliance
2. Guided by the FiO2 required to maintain adequate oxygenation
– PEEP > 5 cm H20 to avoid lung collapse
 ARDSnet Mechanical Ventilation Protocol
Results: Mortality
40
35
30
% Mortality

25
6 ml/kg
20
12 ml/kg
15
10
5
0

Adapted from Figure 1, page 1306, with permission from The Acute Respiratory Distress
Syndrome Network. N Engl J Med 2000;342:1301-1378
 Mechanical Ventilation
of Severe Sepsis
• Maintain mechanically ventilated patients in a
semirecumbent position (head of the bed raised to 45°)
unless contraindicated (to limit aspiration risk and to
prevent the development of VAP) (1B), between 30° and
45° (2C)

• Drakulovic et al. Lancet 1999; 354:1851-1858

 Sedation and Analgesia in Sepsis
(2008)
Use sedation protocols with a sedation goal for critically ill
mechanically ventilated patients
– Ramsay score: daytime: 2-3, night time: 4-5
• Use either intermittent bolus sedation or continuous
infusion sedation to predetermined end points (sedation
scales), with daily interruption/ lightening to produce
awakening. Re-titrate if necessary (1B)
Kollef, et al. Chest 1998; 114:541-548
Brook, et al. CCM 1999; 27:2609-2615
Kress, et al. NEJM 2000; 342:1471-1477
 Neuromuscular Blockers

• Avoid neuromuscular blockers where possible

– Risk of prolonged neuromuscular blockade following
discontinuation
• Monitor depth of block with train-of-four when
using continuous infusions (1B)
 2008 update

Renal Replacement
• Absence of hemodynamic instability
– Intermittent hemodialysis and continuous venovenous
filtration equal (CVVH)

Grade 2B

• Hemodynamic instability
– CVVH preferred --- to facilitate management
of fluid balance in septic patients, no improved in
regional perfusion and survival benefit
Grade 2D
 Bicarbonate Therapy
 Bicarbonate therapy not recommended to
improve hemodynamics in patients with
hypoperfusion-induced lactic acidemia pH
>7.15
• Will increase Na, fluid overload,
increase lactate and PCO2

Grade 1B

Cooper, et al. Ann Intern Med 1990; 112:492-498

Mathieu, et al. CCM 1991; 19:1352-1356
 Deep Vein Thrombosis Prophylaxis
• Heparin (either UFH 2-3times perday or LMWH
once daily) was recommended in patients with
severe sepsis unless contraindications (1A)
• If contraindication for heparin, use mechanical
prophylactic device (1A)
– Mechanical device (unless contraindicated)
such as graduated compression stockings or
intermittent compression devices
 2008 update

Stress Ulcer prophylaxis

• H2 blocker Grade 1A

• Proton pump inhibitor Grade 1B

• The benefit of prevention of upper GI bleed must

be weighed against the potential effect of an
increased stomach pH on development of
ventilator-associated pneumonia

Intensive Care Med 2006;32:1151-1158

 Monitoring a Child With Septic
Shock.
• Frequent monitoring is
MOST IMPORTANT to recognise and Rx
complications.
1. Pulse 5. Urine output.
2. BP6. ABG
3. Level of
consciousness 7. PT/PTT/PC
4. 02 saturation 8. CVP
 Management- summary.
Five important points
1. ABC, supplement 02 always.
2. IV or IO access and fluid resuscitation upto
60 mL/Kg.
3. Early dopamine infusion @10µg/Kg/min
4. Empirical antibiotic.
5. Frequent monitoring.
Thanks for your attention
Avoid Sepsis