Clinical trial NCT04608331: Dexmedetomidine Supplemented Analgesia in Patients at High-risk of Obstructive Sleep Apnea
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obstructive Sleep Apnea
Analgesia
Dexmedetomidine
High-flow Nasal Cannula
Sleep Quality
Keywords: Obstructive Sleep Apnea
Analgesia
Dexmedetomidine
High-flow nasal cannula
Sleep quality
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2020-10-29
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The percentage of non-rapid eye movement stage 2 (N2) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Secondary outcomes:
measure: Total sleep duration.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Sleep efficiency.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Duration of non-rapid eye movement stage 1 (N1) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Percentage of non-rapid eye movement stage 1 (N1) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Duration of non-rapid eye movement stage 2 (N2) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Duration of non-rapid eye movement stage 3 (N3) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Percentage of non-rapid eye movement stage 3 (N3) sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Duration of rapid eye movement sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Percentage of rapid eye movement sleep.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
measure: Sleep fragmentation index.
timeFrame: During the night of surgery (from 9 pm on the day of surgery to 6 am on the first day after surgery)
Other outcomes:
measure: Sedation level
timeFrame: Up to 5 days after surgery.
measure: Cumulative morphine consumption
timeFrame: Up to 5 days after surgery.
measure: Pain intensity
timeFrame: Up to 5 days after surgery.
measure: Subjective sleep quality during the first 5 days after surgery.
timeFrame: Up to the fifth day after surgery.
measure: Incidence of delirium during the first 5 days after surgery.
timeFrame: Up to the fifth day after surgery.
measure: Length of stay in hospital after surgery
timeFrame: Up to 30 days after surgery
measure: Incidence of postoperative complications within 30 days
timeFrame: Up to 30 days after surgery
measure: All-cause 30-day mortality
timeFrame: Up to 30 days after surgery
measure: Quality of life in 30-day survivors
timeFrame: At 30 days after surgery
measure: Cognitive function in 30-day survivors
timeFrame: At 30 days after surgery
measure: The overall subjective sleep quality in 30-day survivors
timeFrame: At 30 days after surgery
Locations:
city: Beijing
country: China
facility: Dong-Xin Wang
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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