Outcomes of vasopressin receptor agonists versus norepinephrine in adults with perioperative hypotension: A systematic review

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogues. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was prospectively registered (CRD42022316328). Literature searches were conducted by a medical librarian to November 28th, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. We included RCTs enrolling adults (≥18) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by RoB-2. Thirteen (N=719) RCTs were included, of which 8 (N=585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, while the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock following cardiac surgery, vasopressin was associated with significantly lower ICU (N=385; 2 trials; mean 100.8 versus 175.2 hours, P<0.005; median 120 [IQR 96-168] versus 144 [96-216] hours, P=0.007) and hospital length of stay, as well as fewer cases of AKI and atrial fibrillation compared to norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of AKI versus norepinephrine overall. Vasopressin and norepinephrine restored MAP with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher MAPs versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among non-cardiac surgical patients and those treated with vasopressin analogues.