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.
This protocol describes a multicentre, double-blind, randomized controlled trial designed to determine whether ephedrine is superior to phenylephrine in reducing postoperative delirium in elderly patients undergoing major non-cardiac, non-neurosurgical surgery.
Key Findings
Methods
The trial will enroll 1,084 elderly patients across seven hospitals in China to compare ephedrine versus phenylephrine for intraoperative hypotension management.
Participants will be randomized in a 1:1 ratio, stratified by study centre
All patients will be scheduled for elective non-cardiac and non-neurosurgical major surgeries under general anaesthesia
The trial is registered in the Chinese Clinical Trial Registry (ChiCTR2500115385)
The study is multicentre, randomized, and double-blind in design
Methods
Both study drugs will be administered as continuous intravenous infusions targeting maintenance of mean arterial pressure within 20% of baseline value.
Participants receive either phenylephrine or ephedrine via continuous intravenous infusion
The target blood pressure range is mean arterial pressure within 20% of the baseline value
The intervention is specifically for intraoperative hypotension management
The comparison addresses an area of clinical uncertainty regarding which vasopressor is preferable in elderly surgical patients
Methods
The primary outcome is the incidence of postoperative delirium within 7 days after surgery.
Postoperative delirium incidence will be assessed within 7 days after surgery
Secondary outcomes include severity of postoperative delirium
Additional secondary outcomes include numeric rating scale pain scores at rest and during activity at 24, 48, and 72 hours postoperatively
Further secondary outcomes include 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
Background
The investigators hypothesize that ephedrine is superior to phenylephrine in reducing postoperative delirium in elderly surgical patients.
The hypothesis is based on the uncertain comparative efficacy of these two vasopressors for postoperative delirium prevention
The target population is described as a 'vulnerable population'
The authors state that 'whether ephedrine, when used to maintain intraoperative blood pressure, is superior to phenylephrine in reducing postoperative delirium remains uncertain'
The findings are anticipated to 'provide high-quality evidence for optimizing the management of intraoperative hypotension in this vulnerable population'
What This Means
This paper describes the protocol (study plan) for a clinical trial that has not yet reported results. The trial is investigating whether a drug called ephedrine works better than another drug called phenylephrine for preventing confusion (called postoperative delirium) in elderly patients after major surgery. Both drugs are used during surgery to keep blood pressure from dropping too low, but it is currently unknown whether one is better than the other for protecting the brain in older patients.
The trial will include 1,084 older patients having major non-heart, non-brain surgeries at seven hospitals in China. Patients will be randomly assigned to receive either ephedrine or phenylephrine during their operation, and neither the patients nor the medical team will know which drug is being used. Researchers will then check whether patients develop delirium in the week after surgery, and also track outcomes like pain levels, time spent in intensive care, length of hospital stay, serious heart or brain complications, and whether patients survive to 30 days.
This research suggests that the choice of blood pressure medication during surgery may matter for elderly patients' mental recovery after an operation. If ephedrine is found to reduce postoperative delirium more effectively than phenylephrine, it could influence how anesthesiologists manage blood pressure in older surgical patients worldwide. Postoperative delirium is a serious complication in elderly patients that can lead to longer hospital stays, cognitive decline, and higher mortality, so identifying preventable causes is clinically important.
Xu X, Wang G, Li X, Peng K, Liu H, Ji F, et al.. (2026). 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.. Annals of medicine. https://doi.org/10.1080/07853890.2026.2732555