Remimazolam for Postoperative Sleep in Elderly Patients

Официальное название

Remimazolam and Postoperative Sleep in Elderly Patients Undergoing Laparoscopic Colorectal Cancer Resection: A Randomized, Double-Blind, PSG-Based Controlled Trial

Обзор

Postoperative sleep disturbance (PSD) is highly prevalent in elderly patients undergoing laparoscopic radical resection of colorectal cancer. Although remimazolam has shown favorable sedative properties and may alleviate perioperative stress, its effects on postoperative sleep architecture remain poorly understood. Polysomnography (PSG), the gold standard for objective sleep assessment, has not been widely used to evaluate these effects in this population. Therefore, this study employs a randomized controlled trial design to verify whether remimazolam is superior to propofol in preserving postoperative sleep quality, thereby offering more evidence-based options for anesthetic management in elderly patients undergoing laparoscopic colorectal cancer surgery.

Подробное описание

Laparoscopic radical resection of colorectal cancer is the most commonly used surgical approach for colorectal cancer in elderly patients. Although this technique is less invasive than traditional open surgery, more than 60% of elderly patients still experience significant sleep fragmentation and disturbance in the early postoperative period, making effective sleep preservation a key component of enhanced recovery after surgery (ERAS).

Sedative agents play a critical role in modulating perioperative sleep patterns. Remimazolam, a novel ultra-short-acting benzodiazepine, is considered a promising anesthetic for elderly patients due to its favorable pharmacokinetic profile and minimal dependence on hepatic and renal function. However, its impact on objective sleep architecture remains unclear. Propofol, the most widely used sedative in general anesthesia, has been reported to disrupt sleep cycles in the postoperative period, with inconsistent effects on slow-wave sleep and rapid eye movement (REM) sleep.

Polysomnography (PSG) is the gold standard for assessing sleep architecture, including total sleep time, sleep efficiency, sleep stage distribution, and arousals. Previous studies have demonstrated that remimazolam is associated with improvements in subjective sleep outcomes in surgical patients. However, current research on remimazolam's effects on postoperative sleep after laparoscopic colorectal cancer surgery remains limited, particularly lacking high-quality, prospective, randomized controlled studies using objective PSG measurements to verify whether remimazolam can achieve superior sleep outcomes compared with propofol. Therefore, this study adopts a randomized controlled trial design to verify whether remimazolam is superior to propofol in preserving postoperative sleep quality, providing more evidence-based options for anesthetic management in elderly patients undergoing laparoscopic radical resection of colorectal cancer.

Вмешательства

• Препарат Remimazolam
  In the remimazolam group, anesthesia was induced with remimazolam 0.2 mg/kg, sufentanil 0.3-0.5 μg/kg, and rocuronium 0.6-0.8 mg/kg. After 3 minutes of preoxygenation, tracheal intubation was performed, and mechanical ventilation was initiated to maintain PETCO₂ at 30-40 mmHg. Anesthesia was maintained with continuous infusions of remimazolam and remifentanil, guided by anesthetic depth monitoring. Rocuronium was supplemented intermittently and discontinued 30 minutes before the end of surgery.P
• Препарат propofol
  In the propofol group, anesthesia was induced with propofol 1.0-1.5 mg/kg, sufentanil 0.3-0.5 μg/kg, and rocuronium 0.6-0.8 mg/kg. Anesthesia was maintained with continuous infusions of propofol and remifentanil. All other procedural details were identical to those in the remimazolam group.

Первичные конечные точки

• Total sleep time (TST) on the first postoperative night [Срок оценки: On the first postoperative night]

Вторичные конечные точки (12)

• Richards-Campbell Sleep Questionnaire (RCSQ) Score [Срок оценки: Postoperative Day 1, Postoperative Day 2, Postoperative Day 3, Postoperative Day 7]
• Pittsburgh Sleep Quality Index (PSQI) Score [Срок оценки: 1 month postoperatively]
• Resting Visual Analogue Scale (VAS) Pain Score [Срок оценки: at 1, 2, and 3 days postoperatively]
• The incidence of postoperative delirium [Срок оценки: at 1, 2, and 3 days postoperatively]
• Postoperative cognitive function [Срок оценки: at 7 days postoperatively and at 1 month postoperatively]
• Sleep efficiency assessed by polysomnography (PSG) [Срок оценки: Postoperative Night 1]
• Number of awakenings after sleep onset assessed by polysomnography (PSG) [Срок оценки: Postoperative Night 1]
• Total wake time assessed by polysomnography (PSG) [Срок оценки: Postoperative Night 1]
• Proportion of each sleep stage assessed by polysomnography (PSG) [Срок оценки: Postoperative Night 1]
• Serum levels of cortisol [Срок оценки: on the morning of postoperative day 1]
• Movement Visual Analogue Scale (VAS) Pain Score [Срок оценки: Postoperative Day 1, Postoperative Day 2, Postoperative Day 3]
• Serum C-reactive protein (CRP) level [Срок оценки: Morning of postoperative day 1]

Критерии участия

Критерии включения

• Aged between 65 and 80 years.
• Scheduled for elective laparoscopic radical resection of colorectal cancer.
• American Society of Anesthesiologists (ASA) physical status class II-III.
• Able to understand the study protocol and provide written informed consent.

Критерии исключения

• Known allergy to any study medications.
• Preoperative sleep disorder (Pittsburgh Sleep Quality Index \[PSQI\] score > 10).
• Regular use of sedatives, antipsychotics or hormonal drugs within the past month.
• Preoperative cognitive impairment, screened using the education-adjusted Mini-Mental State Examination (MMSE).
• Preoperative history of neurological or psychiatric disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety disorders.
• Severe preoperative comorbidities involving the cardiovascular, cerebrovascular, respiratory, hepatic or renal systems, as follows:New York Heart Association (NYHA) functional class IV; current or recent (within 2 months) congestive heart failure; myocardial infarction or coronary stent implantation within the preceding 3 months; Uncontrolled frequent ventricular premature beats (>5 beats per minute), couplets, triplets, paired ventricular arrhythmias, multifocal ventricular premature beats, or R-on-T phenomenon; Second-degree atrioventricular block (Mobitz II type), third-degree atrioventricular block or sick sinus syndrome without pacemaker implantation; Stroke or transient ischemic attack within the preceding 3 months; Severe hypertension (blood pressure ≥ 180/110 mmHg); Severe respiratory tract infection (including common cold), or maximal voluntary ventilation (MMV) < 30% of the predicted value; Severe hepatic dysfunction (Child-Pugh score > 9); Acute or chronic renal failure without renal replacement therapy: Acute kidney injury was defined as an absolute increase in serum creatinine ≥ 0.3 mg/dL (≥26.5 μmol/L) or a relative increase ≥ 50% from baseline, or urine output < 0.5 mL/(kg·h) for more than 6 consecutive hours. Chronic renal failure or uremia was defined as serum creatinine > 451 μmol/L and estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m².
• Severe coagulation disorders.
• Refusal to participate in the trial.
• Anticipated postoperative admission to the intensive care unit (ICU).

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07740343 · RMZ on postoperative sleep

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗