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NCT Number: NCT07789275

Remimazolam Versus Propofol for Maintenance of Anaesthesia During Major Hepatectomy Under Low Central Venous Pressure

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.

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Key information

Conditions

Intraoperative Hypotension Hepatectomy

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Remimazolam

Drug

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.

Propofol

Drug

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.

Primary outcomes

  1. Time-weighted average of mean arterial pressure below 65 mmHg during liver parenchymal transection

    Time frame: 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 outcomes

  1. Cumulative norepinephrine-equivalent dose during liver parenchymal transection

    Time frame: 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.

  2. Number of participants receiving any vasopressor during liver parenchymal transection

    Time frame: 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.

  3. Time-weighted average of mean arterial pressure below 65 mmHg during maintenance anesthesia

    Time frame: 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.

  4. Estimated intraoperative blood loss

    Time frame: 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.

  5. Number of participants receiving intraoperative red blood cell transfusion

    Time frame: During surgery, intraoperative

    The number of participants who receive any red blood cell transfusion during surgery.

  6. Intraoperative red blood cell transfusion dose

    Time frame: During surgery, intraoperative

    The total dose of red blood cells administered to each participant during surgery will be recorded and reported in units.

Other outcomes

  1. Number of participants with acute kidney injury within 7 postoperative days

    Time frame: From the end of surgery through postoperative Day 7

    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.

  2. Number of participants with grade B or C post-hepatectomy liver failure

    Time frame: From postoperative day 5 through hospital discharge, assessed up to postoperative day 30

    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.

  3. Number of participants with severe hypotension during maintenance anesthesia

    Time frame: From the start to the final discontinuation of the allocated maintenance anesthetic, intraoperative

    The number of participants with at least one episode of mean arterial pressure below 55 mmHg lasting at least 1 minute during maintenance anesthesia.

  4. Number of participants with treated bradycardia during maintenance anesthesia

    Time frame: From the start to the final discontinuation of the allocated maintenance anesthetic, intraoperative

    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.

  5. Number of participants with myocardial injury after noncardiac surgery

    Time frame: From approximately 2 hours after surgery on postoperative Day 0 through postoperative Day 3

    The number of participants with myocardial injury after noncardiac surgery. The outcome requires high-sensitivity cardiac troponin I above the assay-specific 99th-percentile upper reference limit, evidence of an acute change from the preoperative value, and blinded adjudication that an ischemic mechanism is the most likely explanation. Only measurements obtained as part of routine clinical care will be used.

  6. Peak postoperative high-sensitivity cardiac troponin I concentration

    Time frame: From approximately 2 hours after surgery on postoperative Day 0 through postoperative Day 3

    The highest high-sensitivity cardiac troponin I concentration recorded from postoperative Day 0 through postoperative Day 3 using measurements obtained as part of routine clinical care. Participation will not require an additional blood draw. Results will be reported using the clinical laboratory assay unit.

  7. Number of participants with study drug-related adverse events

    Time frame: From first exposure to the allocated maintenance anesthetic through postoperative Day 30

    The number of participants with at least one adverse event considered related to the allocated maintenance anesthetic. Events will be assessed from first exposure through postoperative Day 7 or hospital discharge and again at the Day 30 follow-up. Unsolicited events reported between assessments will also be recorded.

  8. Number of participants with study drug-related serious adverse events

    Time frame: From first exposure to the allocated maintenance anesthetic through postoperative Day 30

    The number of participants with at least one serious adverse event considered related to the allocated maintenance anesthetic. Serious adverse events include death, a life-threatening event, substantial prolongation of hospitalization, persistent or clinically important disability, or an intervention required to prevent such an outcome.

  9. Number of participants with All-Cause mortality within 30 days after surgery

    Time frame: From the end of surgery through postoperative Day 30

    The number of participants who die from any cause within 30 days after surgery.

Study contacts

Contact information is provided by the study sponsor or research team.

Zhifeng Gao, MD

CONTACT

[email protected]

+86-15801249466

Sponsors and collaborators

Lead sponsor

Beijing Tsinghua Chang Gung Hospital

Other

Registry information

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 27, 2026
Registry last updated
Aug 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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