The 52 in 52 Review: Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy


    The 52 in 52 Review: Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy

    Article Citation: Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739-46.


    What We Already Know About the Topic: Lactate physiology can assist in triaging the severity of illness for septic patients. While the underlying pathophysiology can be either type A (oxygen-dependent tissue dysoxia) or type B (upregulated sympathomimetic response), the elevation of lactate correlates with illness severity. Central venous oxygen saturation or mixed venous oxygen saturation (ScvO2 or SvO2) is not necessarily required for adequate sepsis resuscitation as seen in the triad of large scale studies (i.e. ProMISe, ARISE, ProCESS) following Rivers’ landmark early goal directed therapy work.


    Why This Study is Important: In the following seven years since this landmark study, the use of lactate clearance has replaced the routine use of ScvO2 to guide resuscitation in sepsis and septic shock. The recent 2016 Surviving Sepsis Guidelines (Rhodes et al 2016) recommend targeting lactate clearance in contrast to the prior 2012 recommendations of targeting ScvO2 or SvO2 of 70% or 65%, respectively.


    Brief Overview of the Study: As a multicenter randomized controlled noninferiority trial, Jones et al assigned 300 severely septic or septic shock patients to either a group targeting ScvO2 of at least 70% or a lactate clearance of 10%. Both groups were resuscitated to normalized central venous pressure (CVP) and mean arterial pressure (MAP). The primary outcome evaluated was absolute in-hospital mortality rate with a noninferiority threshold of Δ -10%. The authors concluded that the intent-to-treat mortality difference of 6% did not meet the predefined -10% threshold.


    Limitations: The lack of blinding in the study makes the finding susceptible to treatment bias. Furthermore, knowledge that the study was ongoing makes the findings susceptible to the Hawthorne effect. Despite the multicenter nature of the trial, the 3 institutions of the study were emergency departments which used quantitative resuscitation; therefore, the findings may not be generalizable to other types of centers.


    Take Home Points: Using lactate clearance as marker for resuscitation of sepsis and septic shock patients is non-inferior to ScvO2 goals. This study’s conclusions have been reflected in the 2016 Surviving Sepsis Guidelines which offer a weak, low quality evidence recommendation for guiding resuscitation with normalizing lactate. There is no longer a goal for ScvO2 or SvO2.




    Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;


    Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.

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