Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial

By A. Jones, N. Shapiro, S. Trzeciak, R. Arnold, H. Claremont, J. Kline. Journal of the American Medical Association (JAMA), 2010

1,049 citations recorded by the source corpus.

Context Goal-directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department. Objective To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation. Design, Setting, and Patients Multicenter randomized, noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals. Interventions We randomly assigned patients to 1 of 2 resuscitation protocols. The ScvO2 group was resuscitated to normalize central venous pressure, mean arterial pressure, and ScvO2 of at least 70%; and the lactate clearance group was resuscitated to normalize central venous pressure, mean arterial pressure, and lactate clearance of at least 10%. The study protocol was continued until all goals were achieved or for up to 6 hours. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. Main Outcome Measure The primary outcome was absolute in-hospital mortality rate; the noninferiority threshold was set at Δ equal to −10%. Results Of the 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographic, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalization. Thirty-four patients (23%) in the ScvO2 group died while in the hospital (95% confidence interval [CI], 17%–30%) compared with 25 (17%; 95% CI, 11%–24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined −10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, −3% to 15%). There were no differences in treatment-related adverse events between the groups. Conclusion Among patients with septic shock who were treated to normalize central venous and mean arterial pressure, additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality.

Subfields: Critical Care and Intensive Care Medicine, Epidemiology, Surgery

View Paper: https://www.semanticscholar.org/paper/ec3b5223998846984b88f96aeb6a83a7b22fb343

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Citations in the corpus

Etiology and therapeutic approach to elevated lactate levels. (2013, methodology): “Previous studies have attempted to use lactate clearance in a more specific manner using a protocol-driven response to persistent elevation.(145,146) Jansen et al(146) studied intensive care unit patients with presumed anaerobic causes of lactate levels of 3 mmol/L or greater and randomized them to ”
Sepsis and septic shock. (2018, background): “86 This approach remains contro versial, however, as hyper lactataemia is not specific to tissue hypo perfusion, and the studies published to date have not found a sufficiently effective protocol that can directly influence serum lactate concentration.”
Learning to Detect Sepsis with a Multitask Gaussian Process RNN Classifier (2017, background): “Unfortunately, early and accurate identification of sepsis remains elusive even for experienced clinicians, as the symptoms associated with sepsis may be caused by many other clinical conditions (Jones et al., 2010).”
An Improved Multi-Output Gaussian Process RNN with Real-Time Validation for Early Sepsis Detection (2017, background): “However, even experienced providers can have signiﬁcant difﬁculty identifying sepsis early and accurately, since the symptoms associated with sepsis can be caused by many other clinical conditions (Jones et al. (2010)).”
The demise of early goal‐directed therapy for severe sepsis and septic shock (2015, background): “This recommendation is based on the notion that an elevated lactate is a consequence of tissue hypoxia and inadequate oxygen delivery,(33) and is ‘supported’ by two studies that used ‘lactate clearance’ as the target of resuscitation.(34,35) However, the concept that sepsis is associated with tissue”