Reducing Mortality in Severe Sepsis and Septic Shock

Andrew T. Levinson, M.D., M.P.H.; Brian P. Casserly, M.D.; Mitchell M. Levy, M.D.


Semin Respir Crit Care Med. 2011;32(2):195-205. 

In This Article

Lactic Acid Clearance

Elevated lactic acid is a marker for the suboptimal supply of oxygen to the tissues and is associated with increased mortality in sepsis. During sepsis, lack of oxygen delivery to the tissues results in decreased cellular metabolism and ultimately an increase in cellular lactate production and subsequent diffusion into the blood.[29] Rising levels of lactic acid are associated with increased mortality and, conversely, decreasing levels are associated with decreased mortality, in patients with septic shock.[46] This association has been found to be independent of degree of organ dysfunction and shock at presentation.[47] A likely more useful parameter for guiding therapy is lactate clearance (the initial lactate - subsequent lactate/initial lactate × 100).[29] A prospective observational study estimated an 11% decrease in mortality for each 10% decrease in lactate clearance.[48] Another recent prospective cohort study also found that lactate nonclearance was a significant independent predictor of death (OR 4.9).[29] A recent prospective study divided patients treated for severe sepsis and septic shock into quartiles of lactate clearance. The study found significantly decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles, and this was associated with decreased levels of biomarkers.[49] Finally, a randomized noninferiority clinical trial found no significant difference in mortality between patients randomized to the use of lactate clearance or ScvO2 as the goal of resuscitation using EGDT.[29] The most recent SSC guidelines recommend beginning resuscitation immediately in patients with hypotension or elevated serum lactate > 4 mmol/L.

SvO2 AND ScvO2

Sepsis can initially result in global tissue hypoxia. Low measurements of the mixed venous oxygen saturation (SvO2) at the level of the pulmonary artery has been associated with poor outcomes in patients with septic shock.[50] Pulmonary artery SvOx2 monitoring requires the placement of a pulmonary artery catheter. The central venous (superior vena cava) oxygen saturation (ScvO2) requires only a central venous catheter and has been used as a surrogate for the balance between systemic oxygen delivery and consumption during the treatment of critically ill patients.[51] A good correlation between ScvO2 and SvO2 was found in critically ill patients.[52] Furthermore, ScvO2 was found in a retrospective cohort study to be an independent predictor of mortality.[53] In the trial by Rivers and colleagues the use of an ScvO2 target above 70% was the only difference in hemodynamic monitoring parameters used in the treatment arm compared with the control group, which resulted in an absolute reduction of mortality by 15%.[35] The mixed SvO2 has been shown on average to run 5 to 7% lower than the ScvO2.[14] The current SSC guidelines recommend targeting an ScvO2 of 70% or a mixed SvO2 of 65% as part of the initial resuscitation protocol.[14] In sepsis, however, it should be noted that the SvO2 may be elevated despite tissue hypoxia, perhaps secondary to maldistribution of flow, leading to concerns that the ScvO2 may not always be a reliable target for quantitative resuscitation because it can at times be normal to elevated despite evidence of significant tissue hypoxia.[33,54] Other theoretical concerns include the possibility that the physiological difference between ScvO2 and SvO2 can be altered if the regional O2 extraction of a certain organ decreases.[55]


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