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The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis*

Jones, Alan E. MD; Brown, Michael D. MD, MSc; Trzeciak, Stephen MD, MPH; Shapiro, Nathan I. MD, MPH; Garrett, John S. MD; Heffner, Alan C. MD; Kline, Jeffrey A. MD on behalf of the Emergency Medicine Shock Research Network investigators

doi: 10.1097/CCM.0b013e318186f839
Feature Articles

Objective: Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on mortality from sepsis.

Data Sources: We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy.

Study Selection: We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality.

Data Abstraction: Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I2 to assess for statistical heterogeneity (p < 0.10, I2 > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals.

Results: The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43–0.96); however, there was statistically significant heterogeneity (p = 0.07, I2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I2 = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37–0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60–2.22).

Conclusion: This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.

From the Department of Emergency Medicine (AEJ, JSG, ACH, JAK), Carolinas Medical Center, Charlotte, NC; Grand Rapids MERC/Michigan State University Program in Emergency Medicine (MDB), Grand Rapids, MI; Department of Emergency Medicine (NIS), Beth Israel Deaconess Medical Center, Boston, MA; and Departments of Emergency Medicine and Medicine, Division of Critical Care Medicine (ST), UMDNJ-Robert Wood Johnson Medical School at Camden, Cooper University Hospital, Camden, NJ.

Supported, in part, by a grant from the National Institute of General Medical Sciences K23GM76652 (AEJ).

Dr. Jones has received unrestricted research support from Critical Biologies Corporation. Dr. Shapiro has received consulting fees, honoraria, and grants from Eli Lilly. Dr. Kline is inventor on US Patent 7,083,574. The remaining authors have not disclosed any potential conflicts of interest.

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins