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

Sponsor

Peking University First Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04608331

Collaborator

(none)

152

Enrollment

Location

Arms

21.9

Anticipated Duration (Months)

6.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea Analgesia Dexmedetomidine High-flow Nasal Cannula Sleep Quality	Drug: Dexmedetomidine Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dexmedetomidine group 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.	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. Other Names: Dexmedetomidine hydrochloride
Placebo Comparator: Placebo group 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.	Drug: 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. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: Dexmedetomidine group

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.

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.

Other Names:

Dexmedetomidine hydrochloride

Placebo Comparator: Placebo group

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.

Drug: 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.

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

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

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.
Subjective sleep quality during the first 5 days after surgery. [Up to the fifth day 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.
Incidence of delirium during the first 5 days after surgery. [Up to the fifth day 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.
Length of stay in hospital after surgery [Up to 30 days after surgery]
Length of stay in hospital after surgery
Incidence of postoperative complications within 30 days [Up to 30 days after surgery]
Postoperative complications are generally defined as newly occurred medical conditions that are deemed harmful and required therapeutic intervention within 30 days after surgery.
All-cause 30-day mortality [Up to 30 days after surgery]
All-cause 30-day mortality
Quality of life in 30-day survivors [At 30 days after surgery]
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.
Cognitive function in 30-day survivors [At 30 days after surgery]
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.
The overall subjective sleep quality in 30-day survivors [At 30 days after surgery]
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.

Other Outcome Measures

Sedation level [Up to 5 days after surgery.]
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.
Cumulative morphine consumption [Up to 5 days after surgery.]
Cumulative morphine consumption
Pain intensity [Up to 5 days after surgery.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >=18 years but <=80 years;
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;
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:

Diagnosed as central sleep apnea syndrome;
Preoperative history of severe central nervous system diseases (epilepsy, parkinsonism, intracranial tumor, craniocerebral trauma) or neuromuscular disorders (myasthenia gravis);
History of schizophrenia or other mental disorders, or antidepressant or anxiolytic therapy within 3 month before surgery;
Inability to communicate in the preoperative period because of coma, profound dementia, deafness or language barriers;
History of drug or alcohol dependence, or sedative or hypnotic therapy within 1 month before surgery;
Contraindications to HFNC therapy (e.g. mediastinal emphysema, shock, cerebrospinal fluid leakage, nasosinusitis, otitis media, glaucoma);
Severe tracheal or pulmonary disease (e.g. bullous lung disease, pneumothorax, tracheal fistula);
Sick sinus syndrome, severe sinus bradycardia (<50 beats per minute), or second-degree or above atrioventricular block without pacemaker；
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;
Preoperative use of CPAP or HFNC therapy;
Expected intensive care unit (ICU) admission with tracheal intubation after surgery;
Refuse to participate in this study;
Other conditions that are considered unsuitable for study participation.