Night-time Dexmedetomidine-esketamine Infusion and Sleep Quality in ICU Patients

NCT05718024 | Completed Phase 4 DMC

• 1 other identifier: 2023-006
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

Dexmedetomidine and ketamine are both suggested for sedation and analgesia in ICU patients. Recent studies suggest that low-dose dexmedetomidine or ketamine/esketamine may improve sleep quality of ICU patients. The purpose of this trial is to observe whether night-time infusion of low-dose dexmedetomidine-esketamine combination can improve sleep structure of patients receiving mechanical ventilation or high-flow nasal cannula oxygen therapy in the ICU.

Conditions

Dexmedetomidine; Intensive Care Unit; Mechanical Ventilation; Esketamine; Sleep Quality

Keywords

Intensive care unit; Mechanical ventilation; Dexmedetomidine; Esketamine; Sleep quality

Outcome Measures

Primary Outcomes (1)

• Percentage of non-rapid eye movement sleep stage 2

  Polysomnographic monitoring is performed during the first night after recruitment with an EEG/PSG Recording System (SOMNO screen plus, SOMNO medics GmbH, Randersacker, Germany). The monitored sleep architecture is divided into wakefulness, non-rapid eye movement (stages N1, N2, and N3) sleep, and rapid eye movement (REM) sleep. The percentages of each sleep stage are calculated as the durations of each sleep stage divided by the total sleep time.

  From 21:00 pm to next 6:00 am during the first night after recruitment

Secondary Outcomes (11)

• Total sleep time

  From 21:00 pm to next 6:00 am during the first night after enrollment

• Sleep efficiency

  From 21:00 pm to next 6:00 am during the first night after enrollment

• Sleep fragmentation index

  From 21:00 pm to next 6:00 am during the first night after enrollment

• Time of sleep in each stage

  From 21:00 pm to next 6:00 am during the first night after enrollment

• Percentage of sleep in each stage (except percentage of non-rapid eye movement sleep stage 2)

  From 21:00 pm to next 6:00 am during the first night after enrollment

Other Outcomes (8)

• Length of hospital stay

  Up to 30 days after enrollment

• Incidence of complications within 30 days

  Up to 30 days after enrollment

• All-cause mortality within 30 days

  Up to 30 days after enrollment

Study Arms (2)

Dexmedetomidine-esketamine

EXPERIMENTAL

Dexmedetomidine-esketamine combination will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy, for a duration of up to 5 days.

Drug: Dexmedetomidine-esketamine

Control

ACTIVE COMPARATOR

Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy (if necessary), for a duration of up to 5 days.

Drug: Routine sedation and analgesia

Interventions

Dexmedetomidine-esketamine DRUG

Dexmedetomidine-esketamine combination will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy.

Dexmedetomidine-esketamine

Routine sedation and analgesia DRUG

Propofol and remifentanil will be infused during night-time (8 pm to 6:30 am) for ICU patients with mechanical ventilation or high-flow nasal cannula oxygen therapy (if necessary).

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 50 years or older;
• Admitted to the intensive care unit (ICU) after surgery;
• Receiving mechanical ventilation or high-flow nasal cannula oxygen therapy during night-time (after 6 pm), with an expected duration of ≥12 hours.

You may not qualify if:

• Duration of invasive/non-invasive ventilation ≥12 hours before enrollment;
• Planning to receive muscle relaxant treatment;
• History of schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis;
• Unable to communicate due to coma, delirium, severe dementia, or language barrier before receiving mechanical ventilation or high-flow nasal cannula oxygen therapy;
• Acute stroke or hypoxic encephalopathy, or after craniocerebral injury or neurosurgery;
• Comorbid with hyperthyroidism or pheochromocytoma;
• Taking sedative/hypnotic drugs or analgesics regularly (for more than 1 week) in the last month;
• LVEF\<30%; sick sinus syndrome, severe sinus bradycardia (heart rate\<50 beats/min), atrioventricular block of more than II degree and without pacemaker; or systolic blood pressure \<90 mmHg despite vasopressor infusion;
• Severe liver dysfunction (Child-Pugh C grade), severe renal dysfunction (dialysis), or estimated survival ≤24 hours;
• Diagnosed obstructive sleep apnea, or body mass index \>30 kg/m2;
• Allergies to dexmedetomidine and/or esketamine, or other conditions that are considered unsuitable for study participation;
• Enrolled in other clinical studies.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (45)

• Friese RS. Sleep and recovery from critical illness and injury: a review of theory, current practice, and future directions. Crit Care Med. 2008 Mar;36(3):697-705. doi: 10.1097/CCM.0B013E3181643F29.

  PMID: 18176314 BACKGROUND

• Elliott R, McKinley S, Cistulli P. The quality and duration of sleep in the intensive care setting: an integrative review. Int J Nurs Stud. 2011 Mar;48(3):384-400. doi: 10.1016/j.ijnurstu.2010.11.006. Epub 2010 Dec 24.

  PMID: 21185560 BACKGROUND

• Parsons EC, Kross EK, Caldwell ES, Kapur VK, McCurry SM, Vitiello MV, Hough CL. Post-discharge insomnia symptoms are associated with quality of life impairment among survivors of acute lung injury. Sleep Med. 2012 Sep;13(8):1106-9. doi: 10.1016/j.sleep.2012.05.010. Epub 2012 Jul 2.

  PMID: 22763017 BACKGROUND

• Combes A, Costa MA, Trouillet JL, Baudot J, Mokhtari M, Gibert C, Chastre J. Morbidity, mortality, and quality-of-life outcomes of patients requiring >or=14 days of mechanical ventilation. Crit Care Med. 2003 May;31(5):1373-81. doi: 10.1097/01.CCM.0000065188.87029.C3.

  PMID: 12771605 BACKGROUND

• Granja C, Lopes A, Moreira S, Dias C, Costa-Pereira A, Carneiro A; JMIP Study Group. Patients' recollections of experiences in the intensive care unit may affect their quality of life. Crit Care. 2005 Apr;9(2):R96-109. doi: 10.1186/cc3026. Epub 2005 Jan 31.

  PMID: 15774056 BACKGROUND

• Aurell J, Elmqvist D. Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care. Br Med J (Clin Res Ed). 1985 Apr 6;290(6474):1029-32. doi: 10.1136/bmj.290.6474.1029.

  PMID: 3921096 BACKGROUND

• Friese RS, Diaz-Arrastia R, McBride D, Frankel H, Gentilello LM. Quantity and quality of sleep in the surgical intensive care unit: are our patients sleeping? J Trauma. 2007 Dec;63(6):1210-4. doi: 10.1097/TA.0b013e31815b83d7.

  PMID: 18212640 BACKGROUND

• Gehlbach BK, Chapotot F, Leproult R, Whitmore H, Poston J, Pohlman M, Miller A, Pohlman AS, Nedeltcheva A, Jacobsen JH, Hall JB, Van Cauter E. Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation. Sleep. 2012 Aug 1;35(8):1105-14. doi: 10.5665/sleep.1998.

  PMID: 22851806 BACKGROUND

• Elliott R, McKinley S, Cistulli P, Fien M. Characterisation of sleep in intensive care using 24-hour polysomnography: an observational study. Crit Care. 2013 Mar 18;17(2):R46. doi: 10.1186/cc12565.

  PMID: 23506782 BACKGROUND

• Slatore CG, Goy ER, O'hearn DJ, Boudreau EA, O'Malley JP, Peters D, Ganzini L. Sleep quality and its association with delirium among veterans enrolled in hospice. Am J Geriatr Psychiatry. 2012 Apr;20(4):317-26. doi: 10.1097/JGP.0b013e3182487680.

  PMID: 22367162 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

• 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 BACKGROUND

• 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 BACKGROUND

• Kanji S, Mera A, Hutton B, Burry L, Rosenberg E, MacDonald E, Luks V. Pharmacological interventions to improve sleep in hospitalised adults: a systematic review. BMJ Open. 2016 Jul 29;6(7):e012108. doi: 10.1136/bmjopen-2016-012108.

  PMID: 27473952 BACKGROUND

• Stanchina ML, Abu-Hijleh M, Chaudhry BK, Carlisle CC, Millman RP. The influence of white noise on sleep in subjects exposed to ICU noise. Sleep Med. 2005 Sep;6(5):423-8. doi: 10.1016/j.sleep.2004.12.004. Epub 2005 Mar 31.

  PMID: 16139772 BACKGROUND

• Freedman NS, Gazendam J, Levan L, Pack AI, Schwab RJ. Abnormal sleep/wake cycles and the effect of environmental noise on sleep disruption in the intensive care unit. Am J Respir Crit Care Med. 2001 Feb;163(2):451-7. doi: 10.1164/ajrccm.163.2.9912128.

  PMID: 11179121 BACKGROUND

• Parthasarathy S, Tobin MJ. Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med. 2002 Dec 1;166(11):1423-9. doi: 10.1164/rccm.200209-999OC. Epub 2002 Sep 5.

  PMID: 12406837 BACKGROUND

• Cooper AB, Thornley KS, Young GB, Slutsky AS, Stewart TE, Hanly PJ. Sleep in critically ill patients requiring mechanical ventilation. Chest. 2000 Mar;117(3):809-18. doi: 10.1378/chest.117.3.809.

  PMID: 10713011 BACKGROUND

• Fanfulla F, Ceriana P, D'Artavilla Lupo N, Trentin R, Frigerio F, Nava S. Sleep disturbances in patients admitted to a step-down unit after ICU discharge: the role of mechanical ventilation. Sleep. 2011 Mar 1;34(3):355-62. doi: 10.1093/sleep/34.3.355.

  PMID: 21358853 BACKGROUND

• Trompeo AC, Vidi Y, Locane MD, Braghiroli A, Mascia L, Bosma K, Ranieri VM. Sleep disturbances in the critically ill patients: role of delirium and sedative agents. Minerva Anestesiol. 2011 Jun;77(6):604-12.

  PMID: 21617624 BACKGROUND

• Weinhouse GL, Watson PL. Sedation and sleep disturbances in the ICU. Crit Care Clin. 2009 Jul;25(3):539-49, ix. doi: 10.1016/j.ccc.2009.04.003.

  PMID: 19576529 BACKGROUND

• Gabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, Hanly PJ. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. Am J Respir Crit Care Med. 2003 Mar 1;167(5):708-15. doi: 10.1164/rccm.2201090.

  PMID: 12598213 BACKGROUND

• Schiza SE, Simantirakis E, Bouloukaki I, Mermigkis C, Arfanakis D, Chrysostomakis S, Chlouverakis G, Kallergis EM, Vardas P, Siafakas NM. Sleep patterns in patients with acute coronary syndromes. Sleep Med. 2010 Feb;11(2):149-53. doi: 10.1016/j.sleep.2009.07.016. Epub 2010 Jan 18.

  PMID: 20083431 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

• Alexopoulou C, Kondili E, Diamantaki E, Psarologakis C, Kokkini S, Bolaki M, Georgopoulos D. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology. 2014 Oct;121(4):801-7. doi: 10.1097/ALN.0000000000000361.

  PMID: 24988068 BACKGROUND

• Xia ZQ, Chen SQ, Yao X, Xie CB, Wen SH, Liu KX. Clinical benefits of dexmedetomidine versus propofol in adult intensive care unit patients: a meta-analysis of randomized clinical trials. J Surg Res. 2013 Dec;185(2):833-43. doi: 10.1016/j.jss.2013.06.062. Epub 2013 Jul 24.

  PMID: 23910886 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

• Sun YM, Zhu SN, Zhang C, Li SL, Wang DX. Effect of low-dose dexmedetomidine on sleep quality in postoperative patients with mechanical ventilation in the intensive care unit: A pilot randomized trial. Front Med (Lausanne). 2022 Aug 31;9:931084. doi: 10.3389/fmed.2022.931084. eCollection 2022.

  PMID: 36117973 BACKGROUND

• Barrett W, Buxhoeveden M, Dhillon S. Ketamine: a versatile tool for anesthesia and analgesia. Curr Opin Anaesthesiol. 2020 Oct;33(5):633-638. doi: 10.1097/ACO.0000000000000916.

  PMID: 32826629 BACKGROUND

• Kaur U, Pathak BK, Singh A, Chakrabarti SS. Esketamine: a glimmer of hope in treatment-resistant depression. Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):417-429. doi: 10.1007/s00406-019-01084-z. Epub 2019 Nov 19.

  PMID: 31745646 BACKGROUND

• Song B, Zhu J. A Novel Application of Ketamine for Improving Perioperative Sleep Disturbances. Nat Sci Sleep. 2021 Dec 25;13:2251-2266. doi: 10.2147/NSS.S341161. eCollection 2021.

  PMID: 34992482 BACKGROUND

• Feinberg I, Campbell IG. Ketamine administration during waking increases delta EEG intensity in rat sleep. Neuropsychopharmacology. 1993 Aug;9(1):41-8. doi: 10.1038/npp.1993.41.

  PMID: 8397722 BACKGROUND

• Ahnaou A, Huysmans H, Biermans R, Manyakov NV, Drinkenburg WHIM. Ketamine: differential neurophysiological dynamics in functional networks in the rat brain. Transl Psychiatry. 2017 Sep 19;7(9):e1237. doi: 10.1038/tp.2017.198.

  PMID: 28926001 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

• Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C. A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. J Neurosci. 2008 Apr 9;28(15):4088-95. doi: 10.1523/JNEUROSCI.5510-07.2008.

  PMID: 18400908 BACKGROUND

• Bunney BG, Li JZ, Walsh DM, Stein R, Vawter MP, Cartagena P, Barchas JD, Schatzberg AF, Myers RM, Watson SJ, Akil H, Bunney WE. Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder. Mol Psychiatry. 2015 Feb;20(1):48-55. doi: 10.1038/mp.2014.138. Epub 2014 Nov 4.

  PMID: 25349171 BACKGROUND

• Bartova L, Papageorgiou K, Milenkovic I, Dold M, Weidenauer A, Willeit M, Winkler D, Kasper S. Rapid antidepressant effect of S-ketamine in schizophrenia. Eur Neuropsychopharmacol. 2018 Aug;28(8):980-982. doi: 10.1016/j.euroneuro.2018.05.007. Epub 2018 Jul 2.

  PMID: 30041987 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

• Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Focus (Am Psychiatr Publ). 2019 Jan;17(1):55-65. doi: 10.1176/appi.focus.17105. Epub 2019 Jan 7.

  PMID: 32015715 BACKGROUND

• Segmiller F, Ruther T, Linhardt A, Padberg F, Berger M, Pogarell O, Moller HJ, Kohler C, Schule C. Repeated S-ketamine infusions in therapy resistant depression: a case series. J Clin Pharmacol. 2013 Sep;53(9):996-8. doi: 10.1002/jcph.122. Epub 2013 Jul 24. No abstract available.

  PMID: 23893490 BACKGROUND

• Persson J, Hasselstrom J, Maurset A, Oye I, Svensson JO, Almqvist O, Scheinin H, Gustafsson LL, Almqvist O. Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity. Eur J Clin Pharmacol. 2002 Feb;57(12):869-75. doi: 10.1007/s002280100353.

  PMID: 11936706 BACKGROUND

• Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol. 2016 Oct;82(10):1069-1076. Epub 2016 Jun 21.

  PMID: 27327855 BACKGROUND

• Hu ZC, Xu G, Zhang XW, Ma K, Jin JJ, Li PS. [Meta-analysis of the effects of dexmedetomidine combined with ketamine during dressing changes in burn patients]. Zhonghua Shao Shang Za Zhi. 2020 Jun 20;36(6):458-464. doi: 10.3760/cma.j.cn501120-20190327-00145. Chinese.

  PMID: 32594705 BACKGROUND

• Lee KH, Lee SJ, Park JH, Kim SH, Lee H, Oh DS, Kim YH, Park YH, Kim H, Lee SE. Analgesia for spinal anesthesia positioning in elderly patients with proximal femoral fractures: Dexmedetomidine-ketamine versus dexmedetomidine-fentanyl. Medicine (Baltimore). 2020 May;99(20):e20001. doi: 10.1097/MD.0000000000020001.

  PMID: 32443302 BACKGROUND

• Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.

  PMID: 21818162 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Analgesia

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Anesthesia and Analgesia

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Study Record Dates

• First Submitted: January 29, 2023
• First Posted: February 8, 2023
• Study Start: November 1, 2023
• Primary Completion: April 22, 2025
• Study Completion: May 23, 2025
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)