Clinical efficacy and safety of vasopressin and its analogues in patients with septic shock: a meta-analysis and trial sequential analysis

Abstract

Abstract Background The guidelines recommend norepinephrine as the first-line drug for the treatment of septic shock, with vasopressin as a complementary drug. However, there is currently no conclusive evidence on the difference in clinical outcomes between vasopressin and norepinephrine in the treatment of septic shock. The aim of this updated meta-analysis was to evaluate the safety and efficacy of vasopressors compared to catecholamines in managing septic shock patients. Methods We conducted a study that included literatures published from inception to August 31, 2023, using databases such as MEDLINE (via PubMed), Embase, Web of Science (WOS), and CENTRAL. The study only included articles published in English. Randomized controlled trials (RCTs) that compared vasopressin with catecholamine alone in septic shock patients were included in this meta-analysis. Pooled effects of relative risk (RR) or mean difference (MD) and their corresponding 95% confidence interval (CI) were calculated using a random/fixed-effects model based on the heterogeneity. Results: Twenty-four studies, involving a total of 4080 participants, were included in the analysis. The combined analysis of vasopressin did not show a significant reduction in 28-day/90-day/ICU/hospital mortality or total mortality (RR, 0.95; 95% CI 0.88–1.02; P = 0.14). This finding was further confirmed by sensitive analyses. However, when considering underlying disease in a subgroup analysis, vasopressin demonstrated benefits in reducing mortality (RR, 0.86; 95% CI 0.75–0.99; P = 0.04), while terlipressin performed even better (RR, 0.74; 95% CI 0.62–0.89; P < 0.01). The pooled analysis also indicated a significant reduction in mechanical ventilation duration with vasopressin (MD -0.60, 95% CI -1.10~-0.11, P = 0.02) and lower norepinephrine doses (MD -10.81, 95% CI -16.78~-4.83, P < 0.01). Additionally, the data suggested a 29% decreased risk of renal replacement therapy in the vasopressin group, but a 2.85 times higher risk of digital ischemia. However, there were no significant differences observed in ICU-LOS, SOFA score change, lactate change, and other adverse events. Conclusions: According to research, vasopressin has shown potential in reducing mortality rates among septic shock patients with underlying diseases. Therefore, when treating patients with septic shock, healthcare professionals should carefully consider the benefits and drawbacks of using vasopressin and make a personalized treatment approach.