Dexmedetomidine Supplemented Analgesia in Patients at High-risk of Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

Official title:

Impact of Dexmedetomidine Supplemented Analgesia on Sleep Quality in Patients at High-risk of Obstructive Sleep Apnea After Major Surgery: A Randomized, Double-blind, and Placebo-controlled Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04608331
• Other study ID #: 2020-189
• Status: Completed
• Phase: Phase 4
• Start date: January 29, 2021
• Est. completion date: September 20, 2022

Study information

• Verified date: December 2022
• Source: Peking University First Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obstructive sleep apnea (OSA) is a common sleep disturbance that can cause intermittent hypoxia, hypercapnia, and sleep structure disorders. The presence of OSA is associated with worse outcomes after surgery including increased incidence of complications. High-flow nasal cannula (HFNC) therapy can improve oxygenation of OSA patients by maintaining a certain positive pressure in the nasopharyngeal cavity. Previous studies showed that, dexmedetomidine supplemented analgesia can improve sleep quality and pain relief. The investigators hypothesize that, for high-risk OSA patients following major non-cardiac surgery with HFNC therapy, dexmedetomidine supplemented analgesia can improve sleep quality. The purpose of this pilot randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on sleep quality in high-risk OSA patients after major non-cardiac surgery.

Description:

Obstructive sleep apnea (OSA) is a common sleep disturbance that can cause intermittent hypoxia, hypercapnia, and sleep structure disorders; the latter include prolonged sleep latency, shortened sleep duration, frequent wake-up, and disordered circadian rhythm. During the postoperative period, surgical stress, pain and the residual effects of sedatives/analgesics can aggravate the sleep disorder and physiological changes in OSA patients. The resulting consequence is increased incidence of postoperative complications.

High-flow nasal cannula (HFNC) therapy can improve the oxygenation of OSA patients by forming a certain positive pressure in the nasopharyngeal cavity. Previous studies showed that HFNC therapy can reduce respiratory events, improve oxygenation in patients with moderate to severe OSA.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedative, analgesic and anti-anxiety properties. Unlike other sedative agents, dexmedetomidine exerts its sedative effects through an endogenous sleep-promoting pathway, producing a state like non-rapid eye movement sleep without disturbing respiration. Our previous studies shows that dexmedetomidine supplemented analgesia can improve sleep quality and pain relief in patients after surgery.

The investigators hypothesize that, for patients at high-risk of OSA who are recovering from major non-cardiac surgery and receiving HFNC therapy, dexmedetomidine supplemented analgesia can improve sleep quality and postoperative recovery. The purpose of this pilot randomized controlled trial is to investigate the impact of dexmedetomidine supplemented analgesia on the sleep quality in high-risk OSA patients after major non-cardiac surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: September 20, 2022
• Est. primary completion date: August 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age >=18 years but <=80 years;

2. At high-risk of obstructive sleep apnea (a STOP-Bang score =3 combined with a serum bicarbonate =28 mmol/ L), but does not regularly receive continuous positive airway pressure (CPAP) therapy;

3. Scheduled to undergo major noncardiac surgery under general anesthesia, with an expected duration of >=1 hours and planned to use patient-controlled intravenous analgesia (PCIA) after surgery.

Exclusion Criteria:

1. Diagnosed as central sleep apnea syndrome;

2. Preoperative history of severe central nervous system diseases (epilepsy, parkinsonism, intracranial tumor, craniocerebral trauma) or neuromuscular disorders (myasthenia gravis);

3. History of schizophrenia or other mental disorders, or antidepressant or anxiolytic therapy within 3 month before surgery;

4. Inability to communicate in the preoperative period because of coma, profound dementia, deafness or language barriers;

5. History of drug or alcohol dependence, or sedative or hypnotic therapy within 1 month before surgery;

6. Contraindications to HFNC therapy (e.g. mediastinal emphysema, shock, cerebrospinal fluid leakage, nasosinusitis, otitis media, glaucoma);

7. Severe tracheal or pulmonary disease (e.g. bullous lung disease, pneumothorax, tracheal fistula);

8. Sick sinus syndrome, severe sinus bradycardia (<50 beats per minute), or second-degree or above atrioventricular block without pacemaker;

9. 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%); ASA classification IV or above; or expected survival <24 hours after surgery;

10. Preoperative use of CPAP or HFNC therapy;

11. Expected intensive care unit (ICU) admission with tracheal intubation after surgery;

12. Refuse to participate in this study;

13. Other conditions that are considered unsuitable for study participation.

Related Conditions & MeSH terms

• Analgesia
• Apnea
• Dexmedetomidine
• High-flow Nasal Cannula
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Sleep Quality

Intervention

Drug:
• Dexmedetomidine
Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours. The pump is established with morphine (0.5 mg/ml) and dexmedetomidine (1.25 microgram/ml), in a total volume of 160 ml normal saline, and programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate of 1 ml/h.
• Placebo
Patient-controlled analgesia is provided for at least 24 hours but no more than 48 hours. The pump is established with morphine (0.5 mg/ml), in a total volume of 160 ml normal saline, and programmed to deliver 2-ml boluses at 6 to 8-minute lockout intervals with a background infusion rate of 1 ml/h.

Locations

Country	Name	City	State
China	Dong-Xin Wang	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (19)

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Chung F, Abdullah HR, Liao P. STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea. Chest. 2016 Mar;149(3):631-8. doi: 10.1378/chest.15-0903. Epub 2016 Jan 12. — View Citation

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Helviz Y, Einav S. A Systematic Review of the High-flow Nasal Cannula for Adult Patients. Crit Care. 2018 Mar 20;22(1):71. doi: 10.1186/s13054-018-1990-4. — View Citation

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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. — View Citation

Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, Tsubosa Y, Satoh T, Yokomizo A, Fukuda H, Sasako M. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016 Jun;46(6):668-85. doi: 10.1007/s00595-015-1236-x. Epub 2015 Aug 20. — View Citation

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McGinley BM, Patil SP, Kirkness JP, Smith PL, Schwartz AR, Schneider H. A nasal cannula can be used to treat obstructive sleep apnea. Am J Respir Crit Care Med. 2007 Jul 15;176(2):194-200. doi: 10.1164/rccm.200609-1336OC. Epub 2007 Mar 15. — View Citation

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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. — View Citation

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sedation level	Sedation level is assessed with the Richmond Agitation Sedation Scale (RASS), with scores ranging from -5 (unarousable) to +4 (combative) and 0 indicates alert and calm.	Up to 5 days after surgery.
Other	Cumulative morphine consumption	Cumulative morphine consumption	Up to 5 days after surgery.
Other	Pain intensity	Pain intensity is assessed twice daily (8-10 am and 18-20 pm) with the numeric rating scale, an 11-point scale where 0=no pain and 10=the worst pain.	Up to 5 days after surgery.
Other	Subjective sleep quality during the first 5 days after surgery.	Subjective sleep quality is assessed daily (8-10 am) with the Richards-Campbell Sleep Questionnaire; which assesses subjective sleep quality in 5 aspects, each scale ranges from 0 to 100, with higher score indicating better function.	Up to the fifth day after surgery.
Other	Incidence of delirium during the first 5 days after surgery.	Delirium is assessed twice daily (8-10 am and 18-20 pm) with the 3D-Confusion Assessment Method for non-intubated patients or the Confusion Assessment Methods for the Intensive Care Unit for intubated patients.	Up to the fifth day after surgery.
Other	Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Other	Incidence of postoperative complications within 30 days	Postoperative complications are generally defined as newly occurred medical conditions that are deemed harmful and required therapeutic intervention within 30 days after surgery.	Up to 30 days after surgery
Other	All-cause 30-day mortality	All-cause 30-day mortality	Up to 30 days after surgery
Other	Quality of life in 30-day survivors	Quality of life is assessed with World Health Organization Quality of Life brief version (WHOQOL-BREF), a 24-item questionnaire that provides assessments of the quality of life in physical, psychological, social relationship, and environmental domains. For each domain, the score ranges from 0 to 100, with higher score indicating better function.	At 30 days after surgery
Other	Cognitive function in 30-day survivors	Cognitive function of 30-day survivors is assessed with the modified Telephone Interview for Cognitive Status (TICSm), a 12-item questionnaire that provides an assessment of global cognitive function by verbal communication via telephone. The score ranges from 0 to 48, with higher score indicating better function.	At 30 days after surgery
Other	The overall subjective sleep quality in 30-day survivors	Assessed with the Pittsburgh Sleep Quality Index, which estimates overall subjective sleep quality in the past 30 days. Overall score ranges from 0 to 21, with higher score indicating better sleep.	At 30 days after surgery
Primary	The percentage of non-rapid eye movement stage 2 (N2) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Total sleep duration.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Sleep efficiency.	The ratio between the total sleep time and the total recording time and expressed as percentage. Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Duration of non-rapid eye movement stage 1 (N1) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Percentage of non-rapid eye movement stage 1 (N1) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Duration of non-rapid eye movement stage 2 (N2) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Duration of non-rapid eye movement stage 3 (N3) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Percentage of non-rapid eye movement stage 3 (N3) sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Duration of rapid eye movement sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Percentage of rapid eye movement sleep.	Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary	Sleep fragmentation index.	The average number of arousals and awakenings per hour of sleep. Calculated according to polysomnographic monitoring results.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)