Hepatectomy, Intraoperative Hypotension
Conditions
Keywords
Remimazolam, Propofol, Major Hepatectomy, Low Central Venous Pressure, Total Intravenous Anesthesia, Mean Arterial Pressure, Time-Weighted Average, Perioperative Hemodynamics, Liver Parenchymal Transection
Brief summary
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.
Detailed description
Low central venous pressure management is commonly used during major hepatectomy to reduce bleeding from the hepatic veins. However, fluid restriction and the effects of general anesthetics may increase the risk, depth, or duration of intraoperative hypotension. Remimazolam may cause less hypotension than propofol, but evidence during major hepatectomy under low central venous pressure management remains limited. This is an investigator-initiated, single-center, two-arm, parallel-group, randomized superiority trial. The study will enroll 224 adults scheduled for elective resection of at least three Couinaud liver segments. Participants will be assigned in a 1:1 ratio to receive remimazolam or propofol for maintenance of total intravenous anesthesia. Both groups will receive a common etomidate-based induction regimen, the same target depth of anesthesia, continuous invasive arterial pressure monitoring, and standardized protocols for low central venous pressure management and treatment of hypotension. The primary observation period is the complete period of liver parenchymal transection during low central venous pressure management. The primary outcome integrates the depth and duration of mean arterial pressure below 65 mmHg during this period. Additional assessments will examine vasopressor use, blood loss, transfusion, recovery, organ complications, myocardial injury, and adverse events. Participants will be followed through postoperative day 30. The attending anesthesiologist cannot be blinded because remimazolam and propofol differ in appearance, preparation, and administration. Participants will remain unaware of their assigned treatment until postoperative outcome assessment is complete. Postoperative assessors, arterial pressure data reviewers, clinical outcome adjudicators, and the primary statistician will remain blinded to treatment allocation.
Interventions
DRUGRemimazolam
After 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.
DRUGPropofol
After 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.
Sponsors
Beijing Tsinghua Chang Gung Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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 * American Society of Anesthesiologists physical status II or III * Both study anesthesia strategies are considered clinically appropriate * Able to understand the study information and provide written informed consent
Exclusion criteria
* 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 * Massive ascites, recent variceal bleeding, clinically important hypersplenism with severe thrombocytopenia, or portal hypertension sufficient to substantially alter circulatory management * Regular long-term benzodiazepine use, drug dependence, or alcohol misuse expected to affect the pharmacological evaluation * Clinical requirement for an inhalational anesthetic or another maintenance anesthesia strategy incompatible with randomized assignment * Pregnant or breastfeeding * Concurrent participation in another interventional study that may affect the primary outcome * Any other condition that, in the investigator's judgment, makes participation unsafe or prevents completion of the study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted average of mean arterial pressure below 65 mmHg during liver parenchymal transection | From the start to the completion of liver parenchymal transection under low central venous pressure management, intraoperative | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative norepinephrine-equivalent dose during liver parenchymal transection | From the start to the completion of liver parenchymal transection under low central venous pressure management, intraoperative | 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 | From the start to the completion of liver parenchymal transection under low central venous pressure management, intraoperative | 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 | From the start to the final discontinuation of the allocated maintenance anesthetic, intraoperative | 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 | From surgical incision to completion of surgery, intraoperative | The total volume of blood loss during surgery will be estimated from the surgical and anesthesia records and reported in milliliters. |
| Number of participants receiving intraoperative red blood cell transfusion | During surgery, intraoperative | The number of participants who receive any red blood cell transfusion during surgery. |
| Intraoperative red blood cell transfusion dose | During surgery, intraoperative | The total dose of red blood cells administered to each participant during surgery will be recorded and reported in units. |
Countries
China
Contacts
CONTACTZhifeng Gao, MD
Outcome results
None listed