Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery

Официальное название

Effect of Dexmedetomidine-esketamine Combination on Sleep Disturbances After Major Noncardiac Surgery: a Single-center, Randomised, Double-blind, Placebo-controlled Trial

Обзор

Sleep disturbances are common early after major surgery, and are associated with delayed recovery. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery. The purpose of this trial is to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.

Подробное описание

Sleep disturbances after surgery is usually manifested as sleep deprivation, altered circadian rhythm, and disturbed sleep structure. The reported incidence of sleep disturbances was 31.4% after gynecologic surgery, 31.9% after urologic surgery, and 35.9% after spine surgery. The occurrence of sleep disturbances is associated with worse perioperative outcomes, including aggravated pain intensity, increased delirium, higher risk of cardiovascular events, and delayed hospital discharge.

Dexmedetomidine is a high-specific alpha 2-adrenergic agonist with anxiolytic, sedative, and analgesic effects. When used during general anesthesia and for postoperative analgesia, dexmedetomidine is associated with improved analgesia and sleep quality. The effect of dexmedetomidine is dose-dependent. However, even commonly used dosage increases bradycardia and hypotension.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine with a higher affinity for NMDA receptors and is approximately twice as potent as racemic ketamine in analgesia. When used during general anesthesia and for postoperative analgesia, esketamine improves analgesia and reduces opioid consumption, but psychiatric symptoms may occur.

The sedative effect of dexmedetomidine is helpful to relieve psychiatric side effects of ketamine/esketamine. A previous study showed that dexmedetomidine-esketamine combination as a supplement to patient-controlled intravenous analgesia improved postoperative analgesia and subjective sleep quality in patients after scoliosis correction surgery.

This trial is designed to test the hypothesis that dexmedetomidine-esketamine combination used as a supplement during general anesthesia and postoperative intravenous analgesia may reduce sleep disturbances in adult after major noncardiac surgery.

Вмешательства

• Препарат Dexmedetomidine-esketamine combination
  Dexmedetomidine 0.4 μg/kg and esketamine 0.2 mg/kg is infused over 10 minutes before anesthesia induction. Dexmedetomidine 0.20 μg/kg/h and esketamine 0.10 mg/kg/h is then infused until 60 minutes before the expected end of surgery. Patient-controlled intravenous analgesia is established with 100 μg dexmedetomidine, 50 mg esketamine, and 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion ra
• Препарат Placebo
  Placebo (normal saline) is administered in the same rate and volume as that in the dexmedetomidine-esketamine group. Patient-controlled intravenous analgesia is established with 100 μg sufentanil, diluted to 100 mL with normal saline, and programmed to deliver 2-mL boluses with a lock-out interval of 8 minutes and background infusion rate at 1 mL/h for up to 72 hours after surgery.

Первичные конечные точки

• Incidence of sleep disturbances within 3 days after surgery [Срок оценки: Up to 3 days after surgery]

Вторичные конечные точки (5)

• Quality of recovery at 24 hours after surgery [Срок оценки: At 24 hours after surgery]
• Subjective sleep quality in the first 3 nights after surgery. [Срок оценки: Up to 3 days after surgery.]
• Pain intensity both at rest and with movement during the first 3 postoperative days [Срок оценки: Up to 3 days after surgery]
• Anxiety and depression on the third day after surgery [Срок оценки: On the third day after surgery]
• Subjective sleep quality on the 30th day after surgery [Срок оценки: On the 30th day after surgery]

Критерии участия

Критерии включения

• Aged ≥18 years.
• Scheduled for major noncardiac surgery (≥60 minutes) under general anesthesia with an expected end of surgery no later than 18:00 pm.
• Required patient-controlled intravenous analgesia after surgery.

Критерии исключения

• Emergency surgery, transurethral surgery, organ transplantation.
• Pregnant or lactating women.
• Patients who need hypnotics for sleep disturbance or antidepressants for depression prior to surgery.
• History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis.
• Inability to communicate due to coma, severe dementia, or speech disorders, endured hypoxic encephalopathy or traumatic brain injury, or after neurosurgery.
• Comorbid with hyperthyroidism and pheochromocytoma.
• Preoperative left ventricular ejection fraction <30%, sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), atrioventricular block of degree II or higher without pacemaker implantation, or systolic blood pressure below 90 mmHg despite use of vasopressors.
• Diagnosed as sleep apnea, or judged to be at high risk of moderate-to-severe sleep apnea as assessed by STOP-Bang.
• Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (on dialysis), or ASA classification ≥IV.
• Hypersensitive to dexmedetomidine and/or esketamine.
• Other conditions that are deemed unsuitable for study participation.

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

Китай · 1 центр

• Peking University First Hospital — Пекин

Публикации

• Allen RW, Burney CP, Davis A, Henkin J, Kelly J, Judd BG, Ivatury SJ. Deep Sleep and Beeps: Sleep Quality Improvement Project in General Surgery Patients. J Am Coll Surg. 2021 Jun;232(6):882-888. doi: 10.1016/j.jamcollsurg.2021.02.010. Epub 2021 Mar 3. PMID 33675989
• Myles PS, Shulman MA, Reilly J, Kasza J, Romero L. Measurement of quality of recovery after surgery using the 15-item quality of recovery scale: a systematic review and meta-analysis. Br J Anaesth. 2022 Jun;128(6):1029-1039. doi: 10.1016/j.bja.2022.03.009. Epub 2022 Apr 14. PMID 35430086
• Kjolhede P, Langstrom P, Nilsson P, Wodlin NB, Nilsson L. The impact of quality of sleep on recovery from fast-track abdominal hysterectomy. J Clin Sleep Med. 2012 Aug 15;8(4):395-402. doi: 10.5664/jcsm.2032. PMID 22893770
• Gulam S, Xyrichis A, Lee GA. Still too noisy - An audit of sleep quality in trauma and orthopaedic patients. Int Emerg Nurs. 2020 Mar;49:100812. doi: 10.1016/j.ienj.2019.100812. Epub 2020 Jan 30. PMID 32007403
• Ruiz FS, Andersen ML, Guindalini C, Araujo LP, Lopes JD, Tufik S. Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice. Brain Behav Immun. 2017 Mar;61:274-288. doi: 10.1016/j.bbi.2016.12.027. Epub 2017 Jan 7. PMID 28069386
• Chouchou F, Khoury S, Chauny JM, Denis R, Lavigne GJ. Postoperative sleep disruptions: a potential catalyst of acute pain? Sleep Med Rev. 2014 Jun;18(3):273-82. doi: 10.1016/j.smrv.2013.07.002. Epub 2013 Sep 24. PMID 24074687
• Fernandes NM, Nield LE, Popel N, Cantor WJ, Plante S, Goldman L, Prabhakar M, Manlhiot C, McCrindle BW, Miner SE. Symptoms of disturbed sleep predict major adverse cardiac events after percutaneous coronary intervention. Can J Cardiol. 2014 Jan;30(1):118-24. doi: 10.1016/j.cjca.2013.07.009. Epub 2013 Oct 16. PMID 24140074
• Lu Y, Li YW, Wang L, Lydic R, Baghdoyan HA, Shi XY, Zhang H. Promoting sleep and circadian health may prevent postoperative delirium: A systematic review and meta-analysis of randomized clinical trials. Sleep Med Rev. 2019 Dec;48:101207. doi: 10.1016/j.smrv.2019.08.001. Epub 2019 Aug 22. PMID 31505369

Идентификаторы

NCT: NCT06859892 · 2024-729

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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