Early Use of Norepinephrine in High-risk Patients Undergoing Major Abdominal Surgery: A Randomized Controlled Trial

Background: Intraoperative hypotension is a strong predictor of adverse outcomes in major abdominal surgery. However, data on the occurrence of intraoperative hypotension during the induction of general anesthesia are scarce. We hypothesized that early prevention of postinduction hypotension using a vasopressor could reduce postoperative adverse outcomes. Methods: In this single-center randomized trial at Amiens Hospital University (Amiens, France), adults older than 50 yr with American Society of Anesthesiologists (Schaumburg, Illinois) Physical Status II or greater undergoing major abdominal surgery were assigned to ephedrine or norepinephrine groups. In the ephedrine group, titration with iterative boluses of ephedrine (3 mg · ml -1 ) was performed at the induction if intraoperative hypotension occurred. In the norepinephrine group, continuous intravenous injection of norepinephrine (0.016 mg · ml -1 ) was started at a rate of 0.48 mg · h -1 from the induction of anesthesia and was titrated if intraoperative hypotension occurred. The primary endpoint was any medico-surgical complication within 30 days (Clavien–Dindo score of 1 or greater). Secondary endpoints included hospital stay length, acute kidney injury, 1-month mortality, and cardiovascular, respiratory, neurologic, and infectious complications. Results were assessed by blinded evaluators. Results: A total of 500 patients were randomized, and 473 were included in the intention-to-treat analysis. The cumulative episodes of intraoperative hypotension were significantly lower in the norephedrine group in comparison to the ephedrine group (respectively, 35 [15%] vs. 176 [74%]; P < 0.001). The primary endpoint occurred in 137 patients (58%) in the ephedrine group and 103 patients (44%) in the norepinephrine group (relative risk, 0.58 [0.40 to 0.83]; P = 0.004). No significant differences were observed in secondary endpoints, except for pulmonary complications, which were lower in the norepinephrine group than in the ephedrine group (respectively; 40 [17%] vs. 74 [31%]; relative risk, 0.46 [0.29; 0.70]; P < 0.001). Conclusions: Prophylactic titrated norepinephrine infusion to prevent postinduction hypotension was more effective than repeated ephedrine boluses and may reduce postoperative complications in major abdominal surgery.