Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia in Patients at High-risk of OSA

NCT06566482 | Recruiting Phase 4

• 1 other identifier: 2024-234
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with obstructive sleep apnea (OSA) are at increased risk of developing sleep disturbances after surgery. Dexmedetomidine is a highly selective α2-adrenergic agonist with sedative, analgesic, and anxiolytic effects. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine and twice as potent as racemic ketamine for analgesia. A recent trial showed that mini-dose esketamine-dexmedetomidine in combination with opioids improved analgesia and subjective sleep quality after scoliosis correction surgery. This trial is designed to test the hypothesis that mini-dose dexmedetomidine-esketamine supplemented analgesia may improve postoperative sleep quality in patients at high-risk of OSA.

Conditions

Obstructive Sleep Apnea; Surgery; Dexmedetomidine; Esketamine; Postoperative Sleep Quality

Keywords

Obstructive Sleep Apnea; Surgery; Dexmedetomidine; Esketamine; Postoperative sleep quality

Outcome Measures

Primary Outcomes (1)

• Subjective sleep quality during the first night after surgery.

  Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure of subjective sleep quality with 5 items, including sleep depth, sleep latency, awakening, return to sleep, and overall sleep quality; the score of each item ranges from 0 to 100, with a higher score indicating better sleep.

  During the first night after surgery.

Secondary Outcomes (5)

• Sleep structure parameters during the first night after surgery.

  During the first night after surgery

• Cumulative subjective sleep quality score after surgery

  During the first three nights after surgery.

• Proportion of patients with poor sleep quality after surgery.

  During the first three nights after surgery.

• Area under curve of pain intensity score within 3 days after surgery.

  Up to 3 days after surgery.

• Subjective sleep quality at 30 days after surgery.

  At 30 days after surgery.

Other Outcomes (5)

• Sedation level within 3 days after surgery.

  Up to 3 days after surgery.

• Length of stay in hospital after surgery.

  Up to 30 days after surgery.

• Incidence of delayed neurocognitive recovery.

  At 30 days after surgery.

Study Arms (2)

Dexmedetomidine-esketamine combination

EXPERIMENTAL

Patient-controlled analgesia is established with dexmedetomidine (1 μg/ml), esketamine (1 mg/ml), and sufentanil (1 μg/ml) in a total volume of 100 ml. The pump is programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate at 1 ml/h. Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours after surgery.

Drug: Dexmedetomidine-esketamine combination

Placebo

PLACEBO COMPARATOR

Patient-controlled analgesia is established with sufentanil (1 μg/ml) in a total volume of 100 ml. The pump is programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate at 1 ml/h. Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours after surgery.

Drug: Placebo

Interventions

Dexmedetomidine-esketamine combination DRUG

Patient-controlled analgesia is established with dexmedetomidine (1 μg/ml), esketamine (1 mg/ml), and sufentanil (1 μg/ml) in a total volume of 100 ml. The pump is programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate at 1 ml/h. Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours after surgery.

Also known as: Dexmedetomidine-esketamine group

Dexmedetomidine-esketamine combination

Placebo DRUG

Patient-controlled analgesia is established with sufentanil (1 μg/ml) in a total volume of 100 ml. The pump is programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate at 1 ml/h. Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours after surgery.

Also known as: Placebo group

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years but ≤80 years;
• Preoperative diagnosis of OSA, or judged to be at moderate-to-high risk of OSA according to the STOP-Bang Questionnaire;
• Scheduled to undergo thoracoscopic or laparoscopic surgery under general anesthesia, with an expected surgical duration of ≥1 hours, and required patient-controlled intravenous analgesia (PCIA) after surgery.

You may not qualify if:

• Diagnosed as central sleep apnea syndrome;
• Previous history of schizophrenia, epilepsy, Parkinson disease, or myasthenia gravis.
• History of schizophrenia, or having antipsychotic drugs (including antidepressants or anxiolytics);
• Inability to communicate in the preoperative period because of coma, profound dementia, or deafness;
• History of drug or alcohol dependence, or sedative or hypnotic therapy within 1 month before surgery;
• Contraindications to ketamine (such as hyperthyroidism, pheochromocytoma, or glaucoma);
• Sick sinus syndrome, severe sinus bradycardia (\<50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
• Contraindications to high-flow nasal cannula therapy (such as mediastinal emphysema, shock or hypotension, cerebrospinal fluid leakage, nasosinusitis, otitis media, or deviation of nasal septum);
• Severe hepatic dysfunction (Child-Pugh class C), severe renal dysfunction (requirement of renal replacement therapy), severe heart dysfunction (preoperative New York Heart Association functional classification ≥3 or left ventricular ejection fraction \<30%), or ASA classification IV or above;
• Expected intensive care unit (ICU) admission with tracheal intubation after surgery;
• Other conditions that are considered unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Related Publications (31)

• Gottlieb DJ, Punjabi NM. Diagnosis and Management of Obstructive Sleep Apnea: A Review. JAMA. 2020 Apr 14;323(14):1389-1400. doi: 10.1001/jama.2020.3514.

  PMID: 32286648 BACKGROUND

• Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pepin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019 Aug;7(8):687-698. doi: 10.1016/S2213-2600(19)30198-5. Epub 2019 Jul 9.

  PMID: 31300334 BACKGROUND

• Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep. 1997 Sep;20(9):705-6. doi: 10.1093/sleep/20.9.705.

  PMID: 9406321 BACKGROUND

• Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Mar 15;13(3):479-504. doi: 10.5664/jcsm.6506.

  PMID: 28162150 BACKGROUND

• Brown KA. Intermittent hypoxia and the practice of anesthesia. Anesthesiology. 2009 Apr;110(4):922-7. doi: 10.1097/ALN.0b013e31819c480a.

  PMID: 19293703 BACKGROUND

• Chung F, Liao P, Yegneswaran B, Shapiro CM, Kang W. Postoperative changes in sleep-disordered breathing and sleep architecture in patients with obstructive sleep apnea. Anesthesiology. 2014 Feb;120(2):287-98. doi: 10.1097/ALN.0000000000000040.

  PMID: 24158049 BACKGROUND

• Hai F, Porhomayon J, Vermont L, Frydrych L, Jaoude P, El-Solh AA. Postoperative complications in patients with obstructive sleep apnea: a meta-analysis. J Clin Anesth. 2014 Dec;26(8):591-600. doi: 10.1016/j.jclinane.2014.05.010. Epub 2014 Oct 16.

  PMID: 25439403 BACKGROUND

• Sun X, Yu J, Luo J, Xu S, Yang N, Wang Y. Meta-analysis of the association between obstructive sleep apnea and postoperative complications. Sleep Med. 2022 Mar;91:1-11. doi: 10.1016/j.sleep.2021.11.019. Epub 2022 Feb 11.

  PMID: 35231774 BACKGROUND

• Lam KK, Kunder S, Wong J, Doufas AG, Chung F. Obstructive sleep apnea, pain, and opioids: is the riddle solved? Curr Opin Anaesthesiol. 2016 Feb;29(1):134-40. doi: 10.1097/ACO.0000000000000265.

  PMID: 26545144 BACKGROUND

• Robertson JA, Purple RJ, Cole P, Zaiwalla Z, Wulff K, Pattinson KT. Sleep disturbance in patients taking opioid medication for chronic back pain. Anaesthesia. 2016 Nov;71(11):1296-1307. doi: 10.1111/anae.13601. Epub 2016 Aug 22.

  PMID: 27545291 BACKGROUND

• Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain. 2013 Dec;14(12):1539-52. doi: 10.1016/j.jpain.2013.08.007.

  PMID: 24290442 BACKGROUND

• Mo Y, Zimmermann AE. Role of dexmedetomidine for the prevention and treatment of delirium in intensive care unit patients. Ann Pharmacother. 2013 Jun;47(6):869-76. doi: 10.1345/aph.1AR708.

  PMID: 23719785 BACKGROUND

• Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.

  PMID: 12552203 BACKGROUND

• Wu Y, Ma R, Zhou Q, Lau HY, Wang Y, Li J, Wen W. Dexmedetomidine-induced polysomnography as a diagnostic method in obstructive sleep apnea: a reliable alternative method? Sleep Med. 2021 Mar;79:145-151. doi: 10.1016/j.sleep.2021.01.005. Epub 2021 Jan 5.

  PMID: 33524840 BACKGROUND

• Guldenmund P, Vanhaudenhuyse A, Sanders RD, Sleigh J, Bruno MA, Demertzi A, Bahri MA, Jaquet O, Sanfilippo J, Baquero K, Boly M, Brichant JF, Laureys S, Bonhomme V. Brain functional connectivity differentiates dexmedetomidine from propofol and natural sleep. Br J Anaesth. 2017 Oct 1;119(4):674-684. doi: 10.1093/bja/aex257.

  PMID: 29121293 BACKGROUND

• Wu XH, Cui F, Zhang C, Meng ZT, Wang DX, Ma J, Wang GF, Zhu SN, Ma D. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016 Nov;125(5):979-991. doi: 10.1097/ALN.0000000000001325.

  PMID: 27571256 BACKGROUND

• Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.

  PMID: 27542303 BACKGROUND

• Zhang ZF, Su X, Zhao Y, Zhong CL, Mo XQ, Zhang R, Wang K, Zhu SN, Shen YE, Zhang C, Wang DX. Effect of mini-dose dexmedetomidine supplemented intravenous analgesia on sleep structure in older patients after major noncardiac surgery: A randomized trial. Sleep Med. 2023 Feb;102:9-18. doi: 10.1016/j.sleep.2022.12.006. Epub 2022 Dec 20.

  PMID: 36587547 BACKGROUND

• Li HJ, Li CJ, Wei XN, Hu J, Mu DL, Wang DX. Dexmedetomidine in combination with morphine improves postoperative analgesia and sleep quality in elderly patients after open abdominal surgery: A pilot randomized control trial. PLoS One. 2018 Aug 14;13(8):e0202008. doi: 10.1371/journal.pone.0202008. eCollection 2018.

  PMID: 30106963 BACKGROUND

• Parvizrad R, Nikfar S. Low-dose ketamine as an analgesic agent in the emergency department: Efficacy and safety. J Family Med Prim Care. 2022 Oct;11(10):6464-6471. doi: 10.4103/jfmpc.jfmpc_511_22. Epub 2022 Oct 31.

  PMID: 36618192 BACKGROUND

• Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018 Dec 20;12(12):CD012033. doi: 10.1002/14651858.CD012033.pub4.

  PMID: 30570761 BACKGROUND

• Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.

  PMID: 29870457 BACKGROUND

• Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sanchez E, Gutierrez-Rojas L, Meana JJ. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.

  PMID: 29736744 BACKGROUND

• Moore TJ, Alami A, Alexander GC, Mattison DR. Safety and effectiveness of NMDA receptor antagonists for depression: A multidisciplinary review. Pharmacotherapy. 2022 Jul;42(7):567-579. doi: 10.1002/phar.2707. Epub 2022 Jun 26.

  PMID: 35665948 BACKGROUND

• Qiu D, Wang XM, Yang JJ, Chen S, Yue CB, Hashimoto K, Yang JJ. Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial. JAMA Netw Open. 2022 Dec 1;5(12):e2244514. doi: 10.1001/jamanetworkopen.2022.44514.

  PMID: 36454569 BACKGROUND

• Duncan WC, Sarasso S, Ferrarelli F, Selter J, Riedner BA, Hejazi NS, Yuan P, Brutsche N, Manji HK, Tononi G, Zarate CA. Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol. 2013 Mar;16(2):301-11. doi: 10.1017/S1461145712000545. Epub 2012 Jun 7.

  PMID: 22676966 BACKGROUND

• Guo J, Qiu D, Gu HW, Wang XM, Hashimoto K, Zhang GF, Yang JJ. Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies. Mol Psychiatry. 2023 Jun;28(6):2266-2276. doi: 10.1038/s41380-023-01945-z. Epub 2023 Jan 20.

  PMID: 36670198 BACKGROUND

• Gregoire C, De Kock M, Henrie J, Cren R, Lavand'homme P, Penaloza A, Verschuren F. Procedural Sedation With Dexmedetomidine in Combination With Ketamine in the Emergency Department. J Emerg Med. 2022 Aug;63(2):283-289. doi: 10.1016/j.jemermed.2022.01.017. Epub 2022 May 9.

  PMID: 35550843 BACKGROUND

• Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023 Aug;131(2):385-396. doi: 10.1016/j.bja.2023.05.001. Epub 2023 Jun 9.

  PMID: 37302963 BACKGROUND

• Chen L, He W, Liu X, Lv F, Li Y. Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial. BMC Anesthesiol. 2023 Jan 27;23(1):34. doi: 10.1186/s12871-023-01994-5.

  PMID: 36707777 BACKGROUND

• Nagappa M, Wong J, Singh M, Wong DT, Chung F. An update on the various practical applications of the STOP-Bang questionnaire in anesthesia, surgery, and perioperative medicine. Curr Opin Anaesthesiol. 2017 Feb;30(1):118-125. doi: 10.1097/ACO.0000000000000426.

  PMID: 27898430 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Dong-Xin Wang, M.D.

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xin-Quan Liang, M.D.

CONTACT

+86 152 1084 6532; liangxinquan09@163.com

Dong-Xin Wang, M.D.

CONTACT

8610 83572784; wangdongxin@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology

Study Record Dates

• First Submitted: August 20, 2024
• First Posted: August 22, 2024
• Study Start: September 11, 2024
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)