The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials

Abstract Purpose Inotropes and vasopressors are cornerstone of therapy in septic shock, but search for the best agent is ongoing. We aimed to determine which vasoactive drug is associated with the best survival. Materials and Methods PubMed, BioMedCentral, Embase and the Cochrane Central Register were searched. Randomized trials performed in septic patient with at least one group allocated to an inotrope/vasopressor were included. Network meta-analysis with a frequentist approach was performed. Results The 33 included studies randomized 3470 patients to 16 different comparators. As compared with placebo, levosimendan (Odds Ratio [OR] = 0.17, 95% Confidence Interval [CI] = 0.05–0.60), dobutamine (OR =0.30, 95% CI = 0.09–0.99), epinephrine (OR =0.35, 95% CI = 0.13–0.96), vasopressin (OR =0.37, 95% CI = 0.16–0.89), and norepinephrine plus dobutamine (OR =0.42, 95% CI = 0.11–0.96) were significantly associated with survival. Norepinephrine improved survival compared with dopamine (OR =0.81, 95% CI = 0.66–1.00). Rank analysis showed that levosimendan had the highest probability of being the best treatment. Conclusions Among several regimens for pharmacological cardiovascular support in septic patients, regimens based on inodilators have the highest probability of improve survival.