The current results, obtained in a population of severe sepsis or septic shock patients, indicate and the prognostic value of lactate clearance in the first 24 hr in ICU. After initial resuscitation, ScvO2 may have poor ability to predict death at day 28.
Mixed central venous oxygen saturation is correlated to the central venous saturation and has been independently associated with mortality in septic shock, with threshold values supporting those published in guidelines . In Varpula’s study a SvcO2 < 70% is independently associated with mortality. Moreover, even if it remains controversial, early goal-directed therapy (H0-H6) adapted to a target of ScvO2 has decreased the mortality rate in septic shock patients .
In the current study, neither static ScvO2 nor ScvO2 variation were predictive for death at day 28 at any time. Other studies performed in intensive care unit after initial resuscitation support these data [20, 21].
These different results are not contradictory. ScvO2 appears to be a useful tool for initial resuscitation but is unable to distinguish survivors and nonsurvivors after this stage. Moreover, if SvcO2 <70% [18, 19] is associated with mortality, it does not mean that SvcO2 ≥70% is associated with survival . ScvO2 seems to be a necessary but not sufficient parameter to guide therapeutic intervention in ICU after initial resuscitation. In ICU-resuscitated patients, ScvO2 or mixed venous oxygen saturation is often larger than 70% despite evidence of abnormal tissue oxygenation. This oxygen extraction defects might be related to severe microcirculatory disorders  and/or mitochondrial damage and/or impairment of cellular respiration  resulting in most of the cases in elevated ScvO2 or SvO2 values [21, 25]. Low levels reflect 1) an inadequate cardiac output with an excessive extraction of oxygen, 2) a low hemoglobin concentration, and/or 3) a low level of arterial oxygen pressure (PaO2). In contrast, high levels of ScvO2 means either 1) a very high oxygen delivery in excess of tissue requirements, and/or 2) decreased cellular consumption of oxygen (mitochondrial dysfunction), and/or 3) more rarely, a large arteriovenous shunt . After early resuscitation, ScvO2 therefore may not be sufficient to guide titration of fluid loading and vasopressor therapy.
In a general ICU population, basal lactate concentration predicted the risk of death with a good accuracy . In 2005, Varpula et al. analyzed hemodynamic parameters in septic shock patients and initial lactate concentration was higher in nonsurvivors (3.4 vs. 2.1 mmol/l respectively, p < 0.005) . In a heterogeneous population of septic patients, blood lactate values, with a threshold of 4 mmo/l, were associated with in-hospital mortality but the predictive value was poor (reported AUC under the ROC curves = 0.56). The lactate concentrations were lower in survivors than in nonsurvivors all along the first 24 hr in ICU and lactate level at H0, even with a threshold of 6.2 mmo/l, indicating therefore a poor ability for death prediction in septic patients.
Several authors have reported that septic patients with the lowest lactate value at H24, even with the same initial lactate concentration, had the highest survival rate [28–30]. For Bakker et al., the “Lactime,” defined as the time passed with a lactate rate above a normal value, was more predictive for death than the initial lactate value . In a cardiac arrest-resuscitated population, lactate levels at admission were not altered in survivors and nonsurvivors patients, whereas lactate clearances were superior in survivors . In hemodynamically stable surgical patients, the association of an occult hypoperfusion with a prolonged hyperlactatemia has been associated with an increased mortality rate . Dynamic assessment of metabolic values may be more efficient for death prediction than static values. Several studies, in severe septic patients, pointed out the value of blood lactate clearance in the first 6 hours of resuscitation for the prediction of day-28 survival [16, 33], but no data are available for longer duration. In the current study, delta lactates until the 24th hour in ICU were predictive for death. Finally, the calculation and interpretation of lactate clearance appeared useful even after the “golden hours” [3, 4] and enable detection of patients with a high risk of death.
For septic patients, a lactate clearance-directed therapy in the first 6 hours appeared as efficient as ScvO2. In a general ICU population, an 8-hour therapy adaptation to lactate clearance reduced the mortality rate in patients with hyperlactatemia compared with standard therapy . No data are available for lactate-directed therapy for longer duration, and no target can thus be proposed. In the study of Jansen et al., a resuscitation adapted to a target of 20% decrease/2 hours for 8 hours decreased the mortality rate . In another recent study, the addition of lactate clearance to the SSC resuscitation bundle is associated with improved outcome . According to this study, absence of lactate clearance during the first 24 hours is associated with mortality in septic ICU patients and should lead to therapy intensification, even in patients who reach standard hemodynamic target.
Several limitations should be considered to interpret this study. First, it was an observational analysis whose results support an association and not necessarily causation. Second, data come from a single center and institution-specific variables may have influenced the present results. Moreover, in the current cohort, following international recommendations , patients with a low ScvO2 have received either dobutamine or transfusion as adapted and these therapeutic-adaptations may have limited our ability to confirm the value of ScvO2 as a prognostic factor.
In conclusion, during severe sepsis or septic shock, blood lactate concentration and lactate clearance are both predictive for 28-day mortality. Assessment of lactate clearance in the first 24 hours would be useful for tracking patients who remained at high risk of death despite achievement of recommended early goals determined by international recommendations. Protocols of prolonged lactate clearance-directed therapy should be evaluated in septic patients.