Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial

Alan E. Jones, Nathan I. Shapiro, Stephen Trzeciak, Ryan C. Arnold, Heather A. Claremont, Jeffrey Kline

Research output: Contribution to journalArticle

665 Citations (Scopus)

Abstract

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. Trial Registration: clinicaltrials.gov Identifier: NCT00372502.

Original languageEnglish (US)
Pages (from-to)739-746
Number of pages8
JournalJournal of the American Medical Association
Volume303
Issue number8
DOIs
StatePublished - Feb 24 2010
Externally publishedYes

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Secondary Prevention
Lactic Acid
Sepsis
Randomized Controlled Trials
Oxygen
Septic Shock
Resuscitation
Arterial Pressure
Central Venous Pressure
Confidence Intervals
Hospital Mortality
Mortality
Hospital Emergency Service
Urban Hospitals
Comorbidity
Patient Care
Hospitalization
Therapeutics
Demography
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy : A randomized clinical trial. / Jones, Alan E.; Shapiro, Nathan I.; Trzeciak, Stephen; Arnold, Ryan C.; Claremont, Heather A.; Kline, Jeffrey.

In: Journal of the American Medical Association, Vol. 303, No. 8, 24.02.2010, p. 739-746.

Research output: Contribution to journalArticle

Jones, Alan E. ; Shapiro, Nathan I. ; Trzeciak, Stephen ; Arnold, Ryan C. ; Claremont, Heather A. ; Kline, Jeffrey. / Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy : A randomized clinical trial. In: Journal of the American Medical Association. 2010 ; Vol. 303, No. 8. pp. 739-746.
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abstract = "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. Trial Registration: clinicaltrials.gov Identifier: NCT00372502.",
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