Comparative efficacy of vasoactive medications in patients with septic shock: a network meta-analysis of randomized controlled trials

Background Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca 2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock. Methods Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed. Results A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% ( n = 1 of 30), followed by EP 3.11% ( n = 5 of 161), and then VP 3.10% ( n = 19 of 613), NE 3.03% ( n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% ( n = 4 of 199), LE 1.16% ( n = 3 of 258), and PA 0.39% ( n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% ( n = 258 of 992), followed by EP 22.98% ( n = 37 of 161), and then NE/DB 20.60% ( n = 41 of 199), NE/EP 20.0% ( n = 6 of 30), NE 8.33% ( n = 127 of 1525), LE 5.81% ( n = 15 of 258), PA 2.33% ( n = 6 of 257), and VP 1.67% ( n = 10 of 600). Conclusions The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.