Menu
Recruiting NCT06859892

Dexmedetomidine-Esketamine Combination and Sleep Disturbances After Major Noncardiac Surgery

Phase IV Interventional Adults Major Noncardiac Surgery Dexmedetomidine Esketamine

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Dexmedetomidine-esketamine combination, Placebo.
Who it may be relevant to
Registry conditions: Adults, Major Noncardiac Surgery, Dexmedetomidine, Esketamine. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Detailed description

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.

Interventions

  • Drug 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
  • Drug 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.

Primary outcome measures

  • Incidence of sleep disturbances within 3 days after surgery [Time frame: Up to 3 days after surgery]
Secondary outcome measures (5)
  • Quality of recovery at 24 hours after surgery [Time frame: At 24 hours after surgery]
  • Subjective sleep quality in the first 3 nights after surgery. [Time frame: Up to 3 days after surgery.]
  • Pain intensity both at rest and with movement during the first 3 postoperative days [Time frame: Up to 3 days after surgery]
  • Anxiety and depression on the third day after surgery [Time frame: On the third day after surgery]
  • Subjective sleep quality on the 30th day after surgery [Time frame: On the 30th day after surgery]

Eligibility criteria

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Prevention

Study locations

China · 1 center
  • Peking University First Hospital — Beijing

Publications

  • 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

Identifiers

NCT: NCT06859892 · 2024-729

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗