Remimazolam Versus Propofol for Early Recovery After Cytoreductive Surgery

Cytoreductive surgery for peritoneal surface malignancies often involves extensive peritoneal stripping, multivisceral resection, major fluid shifts, and prolonged anesthesia. Some patients also receive HIPEC. Propofol may cause vasodilation and cardiovascular depression, whereas remimazolam may provide greater hemodynamic stability. Whether this difference translates into clinically meaningful improvement in overall postoperative recovery remains uncertain.

After written informed consent and completion of baseline assessments, eligible participants will be randomized 1:1 using variable block sizes of 4, 6, or 8, stratified by whether HIPEC is planned. Allocation will be obtained from a permission-controlled electronic randomization system after eligibility is reconfirmed in the operating room and immediately before the first assigned study hypnotic. Participants, postoperative QoR-15 assessors, complication adjudicators, and the primary statistician will remain masked. Anesthesia clinicians cannot be masked because they must titrate the assigned drug.

Both groups will receive bispectral index-guided total intravenous anesthesia with a target BIS of 40 to 60 and standardized principles for analgesia, hemodynamic rescue, temperature management, neuromuscular monitoring, extubation, and intensive care. Surgery end is defined as completion of skin closure, and all postoperative assessment windows are anchored to that time.

The primary outcome is the Chinese QoR-15 total score 48 ± 4 hours after surgery. The primary analysis will use analysis of covariance or an equivalent general linear model with treatment group, baseline QoR-15 score, and planned HIPEC stratum as covariates. The adjusted between-group mean difference, 95% confidence interval, and two-sided P value will be reported. The sample size of 320 provides 90% power to detect a 6-point difference assuming a common standard deviation of 15 and allowing 15% for an unavailable primary outcome or loss to follow-up.

Inclusion criteria

1.Age 18 to 75 years. 2.American Society of Anesthesiologists physical status class II or III. 3.Pathologically confirmed primary peritoneal surface malignancy or peritoneal metastasis from colorectal, gastric, ovarian, or appendiceal malignancy.

4.Scheduled for elective cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy under general anesthesia.

5.Expected surgical duration of at least 2 hours and planned postoperative admission to the intensive care unit.

6.Able to understand and independently complete the Chinese Quality of Recovery-15 questionnaire.

7.Willing to participate and able to provide written informed consent. Exclusion Criteria

• Emergency surgery.
• Uncontrolled bacterial, fungal, or viral infection requiring systemic anti-infective treatment within 14 days before surgery, or temperature of 38.0 °C or higher at post-consent eligibility confirmation with corresponding clinical, imaging, microbiological, or laboratory evidence. Perioperative antimicrobial prophylaxis is not an exclusion.
• Child-Pugh class C, total bilirubin greater than 3 times the upper limit of normal, or alanine or aspartate aminotransferase greater than 5 times the upper limit of normal.
• Estimated glomerular filtration rate below 30 mL/min/1.73 m² or maintenance renal replacement therapy.
• Known allergy to remimazolam, benzodiazepines, propofol, or their excipients, or a contraindication to either study drug.
• Continuous or near-daily opioid use for at least 90 days before surgery, or benzodiazepine or Z-drug use on at least 5 days per week for at least 4 weeks.
• Severe cognitive, psychiatric, hearing, speech, or language impairment that prevents understanding and independent completion of the QoR-15 after standardized explanation.
• Pregnancy or breastfeeding.
• A preoperative plan for continuous epidural analgesia or another continuous regional analgesic technique that is incompatible with the study's standardized intravenous analgesia pathway.
• A specific clinical condition that, in the investigator's judgment, would make participation pose an unacceptable risk.