Efficacy of vasopressin, steroid, and epinephrine protocol for in-hospital cardiac arrest resuscitation: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

Aim: To assess the effect of vasopressin, steroid and epinephrine (VSE) combination therapy on return of spontaneous circulation (ROSC) after in-hospital cardiac arrest (IHCA), and test the conclusiveness of evidence using trial sequential analysis (TSA). Methods: The systematic search included PubMed, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Randomized controlled trials that included adult patients with in-hospital cardiac arrest, with at least one group receiving combined vasopressin, epinephrine and steroid therapy were selected. Data was extracted independently by two reviewers. The main outcome of interest was ROSC. Other outcomes included survival to hospital discharge with good neurological outcomes and survival to 30 and 90 days with good neurological outcomes. Results: We included a total of three randomized controlled trials (n=869 patients). Results showed that Vasopressin, steroid and epinephrine combination therapy increased return of spontaneous circulation (risk ratio, 1.32; 95% CI, 1.18-1.47) as compared to placebo. Trial sequential analysis demonstrated that the existing evidence is conclusive. This was also validated by the alpha-spending adjusted relative risk (1.32 [1.16, 1.49], p<0.0001). Other outcomes could not be meta-analysed due to differences in timeframe in the included studies. Conclusions: VSE combination therapy administered in cardiopulmonary resuscitation led to improved rates of return of spontaneous circulation. Future trials of vasopressin, steroid and epinephrine combination therapy should evaluate survival to hospital discharge, neurological function and long-term survival. Keywords: cardiac arrest; cardiopulmonary resuscitation; meta-analysis; vasopressin; steroid; epinephrine