Effect of phenylephrine versus ephedrine on the incidence of postoperative delirium in elderly patients undergoing non-cardiac and non-neurosurgical procedures: protocol for a multicentre, double-blind, randomized, controlled trial

BACKGROUND: Whether ephedrine, when used to maintain intraoperative blood pressure, is superior to phenylephrine in reducing postoperative delirium remains uncertain. This study aims to determine whether the intraoperative management of hypotension with ephedrine, compared with phenylephrine, reduces the incidence of postoperative delirium in elderly patients undergoing major non-cardiac, non-neurosurgical surgery. METHODS: This multicentre, randomized, double-blind, controlled trial will enrol 1,084 elderly patients scheduled for elective non-cardiac and non-neurosurgical major surgeries under general anaesthesia at seven hospitals in China. Participants will be randomized in a 1:1 ratio, stratified by study centre, to receive continuous intravenous infusion of either phenylephrine or ephedrine to maintain mean arterial pressure within 20% of the baseline value. The primary outcome is the incidence of postoperative delirium within 7 days after surgery. Secondary outcomes include severity of postoperative delirium, numeric rating scale pain scores at rest and during activity at 24, 48 and 72 h postoperatively, intensive care unit (ICU) admission rate and length of ICU stay, length of postoperative hospital stay, incidence of in-hospital major adverse cardiovascular and cerebrovascular events (myocardial infarction, arrhythmia, heart failure, and stroke), and 30-day all-cause mortality. DISCUSSION: We hypothesize that ephedrine, when used to maintain intraoperative blood pressure, is superior to phenylephrine in reducing postoperative delirium in elderly patients undergoing major non-cardiac, non-neurosurgical surgery. The findings of this study may provide high-quality evidence for optimizing the management of intraoperative hypotension in this vulnerable population. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115385).