The effects and safety of vasopressin receptor agonists in patients with septic shock: a meta-analysis and trial sequential analysis

Background: The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock.

Methods: PubMed, EMBASE, and Cochrane library were searched for randomized controlled trials evaluating the effects of vasopressin receptor agonists in septic shock patients. Two reviewers performed literature selection, data extraction, and quality evaluation independently. The primary outcome was mortality. And secondary outcomes included intensive care unit (ICU) length of stay, duration of mechanical ventilation, and incidence of adverse events. In addition, a trial sequential analysis (TSA) was performed.

Results: Twenty studies were eligible for meta-analysis. The results showed vasopressin receptor agonists use was associated with reduced mortality (relative risk (RR) 0.92; 95% confidence interval (CI) 0.84 to 0.99; I² = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) - 0.08, 95% CI, - 0.68 to 0.52, I² = 0%) and duration of mechanical ventilation (MD - 0.58, 95% CI - 1.47 to 0.31, I² = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I² = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I² = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I² = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I² = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I² = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I² = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I² = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I² = 0%) between two groups. Egger's test showed there was no significant publication bias among studies (P = 0.36).

Conclusions: The use of vasopressin might result in reduced mortality in patients with septic shock. An increased risk of digital ischemia must be taken into account.