Impact of Vasodilator Administration on Survival in Patients with Sepsis: A Systematic Review and Meta-Analysis

Rationale: Sepsis and septic shock are associated with microcirculatory dysfunction, which is believed to contribute to sepsis-induced organ failure. Vasodilators have been proposed to improve tissue perfusion in sepsis, but the overall survival impact of this strategy is unclear. Objectives: To evaluate the impact of systemic vasodilator administration in patients with sepsis and septic shock on mortality. Methods: We conducted a meta-analysis using a random effects model. Published and unpublished randomized trials in adult patients with sepsis and septic shock were included when comparing the use of systemic vasodilators against no vasodilators. The primary outcome was 28-30-day mortality, and secondary outcomes were organ function and resource use measures. Results: We included eight randomized trials (1,076 patients). In patients randomized to vasodilator arms compared with those randomized to treatment without vasodilators, the 28-30-day mortality risk ratio was 0.74 (95% confidence interval, 0.54-1.01). In a chronological cumulative meta-analysis, the association between vasodilators and survival improved over time. In a prespecified subgroup analysis in 104 patients in two randomized trials, prostacyclin analogues were associated with a decreased rate of 28-30-day mortality among patients with sepsis and septic shock (risk ratio, 0.46; 95% confidence interval, 0.25-0.85). Conclusions: In patients with sepsis and septic shock, administration of vasodilators is not associated with decreased 28-30-day mortality, but the confidence interval suggests potential benefit, and the meta-analysis might lack power. Prostacyclin appears the most promising. The results of this meta-analysis should encourage randomized trials evaluating the impact of vasodilators on mortality in sepsis.