Remimazolam vs Midazolam to Reduce Delirium in Adults ≥65 Undergoing CPB Valve Surgery

Официальное название

Effect of Remimazolam on Delirium After Cardiac Surgery: Randomized Controlled Trial With Midazolam

Обзор

"Postoperative delirium is a common and serious complication following cardiac surgery, particularly among older adults who require intensive care. Its incidence is reported to range between 20% and 70% after cardiopulmonary bypass (CPB), and has been associated with prolonged hospitalization, increased medical costs, higher morbidity and mortality, and long-term cognitive decline. Benzodiazepines are frequently used during anesthetic induction in cardiac surgery due to favorable hemodynamic stability, although multiple clinical guidelines have recommended limitation of benzodiazepine exposure because of concerns for delirium. However, robust clinical evidence in cardiac surgery remains limited. Midazolam is currently the most commonly administered benzodiazepine in this setting, though metabolism through hepatic pathways and accumulation of active metabolites may increase the risk of postoperative delirium, especially in older patients and those with organ dysfunction. Remimazolam, a recently approved benzodiazepine, undergoes rapid hydrolysis by plasma esterases and demonstrates predictable pharmacokinetic properties with a markedly shorter context-sensitive half-time compared to midazolam. These pharmacologic features suggest a potentially reduced impact on postoperative delirium risk. Despite this rationale, no randomized controlled trial has evaluated the effect of remimazolam versus midazolam on delirium after CPB-assisted valve surgery. This randomized double-blind controlled trial aims to determine whether remimazolam reduces the incidence of postoperative delirium compared with midazolam in patients aged ≥65 years undergoing valve surgery with CPB. Eligible participants will be randomized in a 1:1 ratio to receive either remimazolam or midazolam for anesthetic induction according to a computer-generated allocation sequence. All other anesthetic management will follow standardized institutional protocols, including depth of anesthesia monitoring. Delirium assessment will be performed three times daily in the intensive care unit using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC) and twice daily on the ward using 3-Minute Diagnostic Interview for CAM (3D-CAM) for four postoperative days. The primary endpoint is the incidence of delirium within four postoperative days. Key secondary outcomes include in-hospital or 30-day mortality and a composite of major postoperative complications. A total of 300 patients (150 per group) will be enrolled to provide 90% statistical power to detect the hypothesized difference in delirium risk between groups, accounting for a 10% dropout rate. Findings from this study are expected to provide high-quality evidence regarding the comparative impact of remimazolam and midazolam on postoperative delirium and may inform anesthetic strategy selection in high-risk cardiac surgical populations."

Вмешательства

• Препарат Midazolam
  Participants receive intravenous midazolam 0.05 mg/kg for anesthetic induction and an additional dose (0.065 mg/kg) administered via the cardiopulmonary bypass circuit during rewarming, with all other anesthetic management identical to the experimental arm.
• Препарат Remimazolam
  Participants receive intravenous remimazolam 0.2 mg/kg for anesthetic induction and an additional dose (0.26 mg/kg) administered via the cardiopulmonary bypass circuit during rewarming, together with standard cardiac anesthesia care.

Первичные конечные точки

• Incidence of postoperative delirium within 4 days after surgery [Срок оценки: From the day of surgery (POD 0) to postoperative day 4]

Критерии участия

Критерии включения

• Patients aged 65 years or older undergoing heart valve surgery involving cardiopulmonary bypass.

Критерии исключения

• Emergency surgery, Surgery involving total arch replacement, History of remimazolam anaphylaxis, History of major neurocognitive disorder, Alcohol or substance dependence/abuse, Major depressive disorder, Schizophrenia, Participation in other clinical studies that may affect outcomes, Inability to provide informed consent due to illiteracy, foreign language barrier, or cognitive impairment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

South Korea · 1 центр

• Department of Anaesthesiology and Pain Medicine, Yonsei University College of Medicine — Seoul

Идентификаторы

NCT: NCT07265128 · 4-2024-0976

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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