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

Phase 4

Completed

• Conditions: Obstructive Sleep Apnea; Analgesia; Dexmedetomidine; High-flow Nasal Cannula; Sleep Quality
• Interventions: Drug: Placebo; Drug: Dexmedetomidine

• Registration Number: NCT04608331
• Lead Sponsor: Peking University First Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-27
• Study First Posted: 2020-10-29
• Study Start: 2021-01-29
• Primary Completion: 2022-08-17
• Study Completion: 2022-09-20
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-10
• Last Update Posted: 2022-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	Patient-controlled analgesia is established with morphine (0.5 mg/ml) in a total volume of 160 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 after surgery.
Dexmedetomidine group	Dexmedetomidine	Patient-controlled analgesia is established with morphine (0.5 mg/ml) and dexmedetomidine (1.25 microgram/ml) in a total volume of 160 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 after surgery.

Primary Outcome Measures

Name	Time	Method
The percentage of non-rapid eye movement stage 2 (N2) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.

Secondary Outcome Measures

Name	Time	Method
Total sleep duration.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Sleep efficiency.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	The ratio between the total sleep time and the total recording time and expressed as percentage. Calculated according to polysomnographic monitoring results.
Duration of non-rapid eye movement stage 1 (N1) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Percentage of non-rapid eye movement stage 1 (N1) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Duration of non-rapid eye movement stage 2 (N2) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Duration of non-rapid eye movement stage 3 (N3) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Percentage of non-rapid eye movement stage 3 (N3) sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Duration of rapid eye movement sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Percentage of rapid eye movement sleep.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	Calculated according to polysomnographic monitoring results.
Sleep fragmentation index.	During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)	The average number of arousals and awakenings per hour of sleep. Calculated according to polysomnographic monitoring results.

Trial Locations

Locations (1)

Dong-Xin Wang; 🇨🇳 Beijing, Beijing, China