5.3.1 Severe Sepsis and Septic Shock Management Guideline
The approach below is based largely on the Practice Management Guidelines offered by
the Society of Critical Care Medicine (CCM, 2004, Vol.32, No.9)
Basic Principles:
Septic shock requires early and aggressive resuscitation. An integrated approach directed
at rapidly restoring systemic oxygen delivery and improving tissue oxygenation ahs been
shown to improve survival in septic shock. Therapy should be guided by parameters that
reflect the adequacy of tissue and organ perfusion.
Patients with septic shock should be treated in an intensive care unit setting. Fluid
infusion should be vigorous and titrated to clinical end points of volume repletion.
Systemic oxygen delivery should be aggressively supported by ensuring arterial oxygen
saturation, adequate hemoglobin levels and using vasoactive agents when necessary as
determined by physiologic and clinical endpoints.
Goals and End Points of Hemodynamic Support in Septic Patients:
 Restore effective tissue perfusion
 Normalize cellular metabolism
Indices of Global Perfusion:
Indications of decreased perfusion include:
 Oliguria
 Clouded sensorium
 Delayed capillary refill
 Cool skin
Elevated blood lactate
 trend appears more reliable than isolated number
 better prognostic value than other indices
Mixed venous oxyhemoglobin saturation
 measured with a right heart catheter
 represents balance between delivery and consumption
 dependent on cardiac output, hemoglobin, arterial oxygen saturation
 of caution: can be elevated in sepsis due to maldistribution of blood flow
Indices of Regional Perfusion:
Assessed clinically by evaluating indexes of organ function
 myocardial ischemia
 decreased uring output or increased BUN to creatinine ratio
 abnormal sensorium
 increased serum concentrations of transaminases, lactic dehydrogenase and
bilirubin
 prolonged clotting studies
Treatment Strategies:
Initial Resuscitation Goals:
Aggressive resuscitation of patients with septic shock or elevated serum lactate must be
rapid, or mortality can increase by 30%. The following should be achieved within 4
hours of the onset of septic shock:

Fluid Resuscitation to achieve a goal of
o CVP 8-12 mmHg
o PAO 12-15 mmHg
o EDVI 120-140 ml/M2
o If poor response to fluid challenges consider invasive monitoring



Vasoactive Drugs only after preload is optimal
o To maintain a mean arterial pressure 65-70 mmHg
Inotropic Agents
o appropriate cardiac output (about 1.5 times normal) if myocardial function
is depressed
o a right atrial or mixed venous oxygen saturation of at least 70%
Urine Output
o 0.5-1ml/kg/hour
Source Control:
o Evaluate patient for the presence of a focus of infection amenable to source
control measures
o drainage of an abscess
o debridement of infected tissue
o removal of a potentially infected device
o definitive control of a source of ongoing microbial contamination
Fluid Resuscitation Therapy:
 patients with septic shock can be successfully resuscitated with either crystolloid
or colloid replacement
o more crystalloid will be required to reach same resuscitation goals (2-4X
more volume)
o no mortality differences shown in SAFE trial
o no differences noted in pulmonary edema with either resuscitation mode
 Fluid challenges in patients with perfusion deficits are given rapidly with
predetermined bolus (250-500ml/ 15 minutes) titrated to clinical endpoints
o Initial fluid is a balanced isotonic crystalloid (Normal Saline or Lactated
Ringers solution)
o If response is insufficient or transient consider adding colloid (5%
albumin)
Transfusion Therapy:
o Optimal hemoglobin for patients with septic shock is unknown
o Most patients will tolerate hemoglobin concentrations in the range of 8-10 g/dL
o Red blood cell transfusion to above this level should be limited to the following
circumstances:
o Resuscitated patients with SvO2 <65%
o Active coronary arterial disease with recent angina or coronary
syndrome

Target hemoglobin of 10-12 g/dl
o Acute ongoing hemorrhage in face of anemia (hgb < 9g/dl)
o FFP transfusion
o clinical bleeding
o need to undergo invasive procedure
o Platelet transfusion
o absolute counts < 10,000
o <30,000 and high potential for bleeding
o <50,000 and need to undergo invasive procedure
o Consider the administer erythropoetin 600 u/kg subcutaneously weekly (40,000
units for most typical adults) for hgb < 11 g/dl
Vasopressor Therapy:
o When fluid administration fails to restore adequate arterial pressure and perfusion,
therapy with vasopressor agents should be initiated
o Arterial pressure is the endpoints of vasopressor therapy
 Mean arterial pressure of 60mmHg is required to maintain and
optimize flow
o Individual Agents:
o Norepinephrine: agent of choice
 Potent α-adrenergic agonist with less pronounced β-adrenergic
agonist effects
 Dosage 0.1-3 µg/kg/min
 Doses above 1 mcg/kg/min should initiate re-evaluation for
contributing conditions
o Dopamine:
 Not as effective as norepinephrine
 Use limited by tachycardia
 Dosage
 <5 µg/kg/min predominant effect is to stimulate
dopaminergic receptors
 5-10 µg/kg/min predominant β-adrenergic agonist effects
o increasing contractility and heart rate
 >10 µg/kg/min α-adrenergic agonist effects
o arterial vasoconstriction

low dose not found to be renoprotective and should not be used in
septic shock
o second line agents
 Epinephrine
 Potential adverse effects from splanchnic hypoperfusion
 Phenylephrine
 May decrease stroke volume by increasing afterload
 Vasopressin
 Potent vasoconstrictor by direct constriction of vascular
smooth muscle and increased responsiveness to
catecholamines
 May be effective in patients refractory to other agents
 Use in caution if cardiac dysfunction
 Dosage 0.01-0.04 u/min
o Doses greater than 0.04 u/min are associated
with intestinal ischemia, myocardial ischemia
and cardiac arrest
Inotropic Therapy:
o Dobutamine: first choice
o In patients with low cardiac output despite adequate volume loading, may be
used to increase cardiac output
o If hypotension evident, combine with Vasopressor
Endocrine Therapy:
o Patients with vasopressor dependent septic shock should be tested for relative
adrenal insufficiency
o Dexamethasone can be used while waiting for ACTH stimulation testing
 Dosage: 4-6 mg intravenous q 6 hours
o Intravenous corticosteroids are recommended for nonresponders
 < 9 µg/dL rise after cosyntropin
 dosage: 50 mg hydrocortisone intravenous every 6 hours for 7 days
 consider taper if rebound hypotension after cessation of steroids
o High dose steroids NOT indicated
Recombinant Human Activated Protein C:
o Recommended in patients at high risk of death and with no absolute
contraindications related to bleeding risk or relative contraindications that
outweighs the potential benefit
o High risk of death
 APACHE II score >25
 Sepsis-induced multiple organ failure
 Septic shock
 Sepsis-induced ARDS
o Contraindications
 Active internal bleeding


Recent (within 3 months) hemorrhagic stroke
Recent (within 2 months) intracranial or intraspinal surgery, or
severe head injury
 Trauma with an increased risk of life-threatening bleeding
 Presence of an epidural catheter
 Intracranial neoplasm or mass lesion or evidence of cerebral
herniation
o Refer to Drotrecogin alfa (activated) Order Form for further inclusion/exclusion
Glucose Control:
o Attempts should be made to maintain blood glucose between 80-110 mg/dL
o See insulin drip protocol if necessary