The goal of this clinical trial is to learn whether remimazolam helps prevent low blood pressure better than propofol during major liver surgery in adults. All participants will have planned surgery to remove at least three liver segments.
The main question is whether participants who receive remimazolam have less low blood pressure while the surgeon removes liver tissue. Researchers will measure both how low the blood pressure falls and how long it stays low.
Researchers will randomly assign 224 participants to receive remimazolam or propofol to maintain general anesthesia. Participants will not know which drug they receive until their postoperative assessments are complete. The anesthesiologist giving the drug will know the assignment for safety reasons.
Participants will:
* Receive one of the two study drugs during surgery * Have their blood pressure monitored continuously * Receive standard treatment if their blood pressure becomes low * Complete follow-up through 30 days after surgery
Researchers will also compare the use of medicines to support blood pressure, bleeding, blood transfusion, recovery after anesthesia, organ complications, heart injury, and adverse events.
Age 18 to 85 years
Scheduled for elective liver resection
Preoperative surgical plan includes resection of at least three Couinaud liver segments
Planned use of low central venous pressure management, general anesthesia, invasive arterial pressure monitoring, and central venous pressure monitoring
Emergency surgery or inability to complete written informed consent before surgery
Known contraindication or serious hypersensitivity to remimazolam, another benzodiazepine, propofol, or a relevant excipient
Preoperative shock, ongoing vasoactive drug support, or another hemodynamically unstable condition that makes either study anesthesia strategy unsafe
Child-Pugh class C, Model for End-Stage Liver Disease score of 20 or higher, or end-stage liver disease in the investigator's judgment
Parallel
Remimazolam
DrugAfter a common etomidate-based induction regimen and tracheal intubation, intravenous remimazolam will be infused at 1.0 to 2.0 mg/kg/hour for maintenance of general anesthesia. The dose will be titrated to a bispectral index of 40 to 60, clinical signs, and surgical stimulation. The infusion will be stopped when emergence is planned. Flumazenil will not be administered routinely.
Propofol
DrugAfter a common etomidate-based induction regimen and tracheal intubation, intravenous propofol will be infused at 4.0 to 10.0 mg/kg/hour for maintenance of general anesthesia. The dose will be titrated to a bispectral index of 40 to 60, clinical signs, and surgical stimulation. The infusion will be stopped when emergence is planned.
Time-weighted average of mean arterial pressure below 65 mmHg during liver parenchymal transection
The time-weighted average will quantify the depth and duration of hypotension during the complete period of liver parenchymal transection under low central venous pressure management. It will be calculated from quality-assessed invasive arterial pressure measurements. For periods when mean arterial pressure is below 65 mmHg, the difference between 65 mmHg and the observed pressure will be integrated over time. The resulting area will be divided by the duration of valid arterial pressure monitoring. The unit is mmHg. A value of 0 indicates that no valid mean arterial pressure measurement was below 65 mmHg. Higher values indicate a greater hypotension burden.
Cumulative norepinephrine-equivalent dose during liver parenchymal transection
The total dose of vasopressors administered during the complete liver parenchymal transection period under low central venous pressure management will be converted to norepinephrine equivalents using conversion rules prespecified before the first randomization. The cumulative dose will be normalized to body weight and reported in micrograms/kg.
Number of participants receiving any vasopressor during liver parenchymal transection
The number of participants who receive at least one vasopressor bolus or infusion during the complete liver parenchymal transection period under low central venous pressure management. Vasopressors include norepinephrine, ephedrine, and any other vasoactive drug administered to support arterial pressure.
Time-weighted average of mean arterial pressure below 65 mmHg during maintenance anesthesia
The time-weighted average will quantify the depth and duration of mean arterial pressure below 65 mmHg over the entire period of allocated maintenance anesthesia. For periods when mean arterial pressure is below 65 mmHg, the difference between 65 mmHg and the observed pressure will be integrated over time and divided by valid monitored time. The unit is mmHg. Higher values indicate a greater hypotension burden.
Estimated intraoperative blood loss
The total volume of blood loss during surgery will be estimated from the surgical and anesthesia records and reported in milliliters.
Number of participants with acute kidney injury within 7 postoperative days
The number of participants who develop acute kidney injury within 7 days after surgery according to Kidney Disease: Improving Global Outcomes criteria, based on postoperative serum creatinine and urine output information available in the clinical record.
Number of participants with grade B or C post-hepatectomy liver failure
The number of participants who develop grade B or C post-hepatectomy liver failure according to International Study Group of Liver Surgery criteria. Grade A post-hepatectomy liver failure will not be counted in this outcome.
Number of participants with severe hypotension during maintenance anesthesia
The number of participants with at least one episode of mean arterial pressure below 55 mmHg lasting at least 1 minute during maintenance anesthesia.
Number of participants with treated bradycardia during maintenance anesthesia
The number of participants who receive medication or another clinical intervention for bradycardia during maintenance anesthesia. Heart rate below 50 beats/minute will be used to identify bradycardic periods.
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