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 I 2 to assess for statistical heterogeneity (p < 0.10, I 2 > 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, I 2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I 2 = 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). Despite its endorsement by 11 professional societies, the recommendation has produced significant controversy, in part because it relied heavily on one study (6-10).
Conclusion-ThisScientific knowledge is cumulative; therefore new research findings should be interpreted based on what is already known (11). Recognizing that clinical trials of quantitative resuscitation were published for nearly two decades before the Rivers et al. study, we hypothesized that their results could be aggregated to produce more definitive conclusions about the treatment effect of quantitative resuscitation in sepsis. Therefore, we conducted a meta-analysis to examine the available evidence investigating a quantitative resuscitation strategy for patients with sepsis, to determine the treatment effect of such a strategy on mortality, and to determine whether the timing of implementation of quantitative resuscitation impacts mortality.
METHODS
Search Strategy for Identification of StudiesA written protocol following recommended guidelines that was finalized before beginning the study was followed (12). We searched the Cochrane Library, MEDLINE (1965( -August 2007, EMBASE (1974( -Augu...