Sunday, April 06, 2014

Sepsis: changing definitions and recommendations

At UCSF's 17th annual hospital medicine conference Michael A. Gropper, MD, PhD summarized the changes, focusing mainly on changes from 2008 in the 2012 Surviving Sepsis guidelines. Here's my quick and dirty rundown.


Sepsis was formerly defined as documented or suspected infection plus two sirs criteria. In contrast, the 2012 guidelines define it as documented or suspected infection plus “some” of a long list of conditions:

Fever (greater than 38.3°C)
Hypothermia (core temperature less than 36°C)
Heart rate greater than 90/min–1 or more than two sd above the normal value for age
Altered mental status
Significant edema or positive fluid balance (greater than 20 mL/kg over 24 hr)
Hyperglycemia (plasma glucose greater than 140 mg/dL or 7.7 mmol/L) in the absence of diabetes
Leukocytosis (WBC count greater than 12,000 μL–1)
Leukopenia (WBC count less than 4000 μL–1)
Normal WBC count with greater than 10% immature forms
Plasma C-reactive protein more than two sd above the normal value
Plasma procalcitonin more than two sd above the normal value
Arterial hypotension (SBP less than 90 mm Hg, MAP less than 70 mm Hg, or an SBP decrease greater than 40 mm Hg in adults or less than two sd below normal for age) 
Arterial hypoxemia (Pao2/Fio2 less than 300)
Acute oliguria (urine output less than 0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
Creatinine increase greater than 0.5 mg/dL or 44.2 μmol/L
Coagulation abnormalities (INR greater than 1.5 or aPTT greater than 60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count less than 100,000 μL–1)
Hyperbilirubinemia (plasma total bilirubin greater than 4 mg/dL or 70 μmol/L)
Tissue perfusion variables
Hyperlactatemia (greater than 1 mmol/L)


Crystalloid as the initial resuscitation fluid of choice (former guidelines did not specify crystalloid versus colloid). Initial crystalloid amount of 30 ml//kg.

Norepinephrine as the first choice pressor (former guidelines did not specify norepi versus dopamine).

Note that norepinephrine is not always to be delayed until volume resuscitation is complete. From the guideline document:

Vasopressor therapy is required to sustain life and maintain perfusion in the face of life-threatening hypotension, even when hypovolemia has not yet been resolved. Below a threshold MAP, autoregulation in critical vascular beds can be lost, and perfusion can become linearly dependent on pressure. Thus, some patients may require vasopressor therapy to achieve a minimal perfusion pressure and maintain adequate flow (133, 134).

What if norepi isn't enough? The implication is that epinephrine is next followed by vasopressin, but the guidelines lack clarity as to which to use first and why. Again, quoting from the document:

We recommend norepinephrine as the first-choice vaso-pressor (grade 1B).
We suggest epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure (grade 2B).
Vasopressin (up to 0.03 U/min) can be added to norepinephrine with the intent of raising MAP to target or decreasing norepinephrine dosage (UG).

Neuromuscular blockers for ARDS but only early, only if PO2/FiO2 below 150 and only for up to 48 hours. The 2008 guidelines suggested blanket avoidance of neuromuscular blockers.

Relaxed glycemic control targets (180 in the new guidelines as opposed to 150).

Feeding (oral or enteral) within 48 hours onset of severe sepsis or septic shock. Previous guidelines didn't address feeding.

Advance care planning addressed within 72 hours. Previous guidelines did not set a time frame for this.

The guidelines make several additional recommendations about sepsis induced ARDS which are (or will be) addressed in separate posts on that topic.

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