Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia in Patients at High-risk of OSA

September 23, 2024 updated by: Dong-Xin Wang, Peking University First Hospital

Mini-dose Dexmedetomidine-Esketamine Supplemented Analgesia for Postoperative Sleep Promotion in Patients at High-risk of Obstructive Sleep Apnea: A Randomized Trial

Patients with obstructive sleep apnea (OSA) are at increased risk of developing sleep disturbances after surgery. Dexmedetomidine is a highly selective α2-adrenergic agonist with sedative, analgesic, and anxiolytic effects. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine and twice as potent as racemic ketamine for analgesia. A recent trial showed that mini-dose esketamine-dexmedetomidine in combination with opioids improved analgesia and subjective sleep quality after scoliosis correction surgery. This trial is designed to test the hypothesis that mini-dose dexmedetomidine-esketamine supplemented analgesia may improve postoperative sleep quality in patients at high-risk of OSA.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Obstructive sleep apnea (OSA) is characterized by repetitive narrowing or obstruction of the upper airway during sleep, resulting in recurrent hypoxemia and hypercapnia and disordered sleep. During the postoperative period, the residual effects of anesthetics, sedatives, analgesics, and muscle relaxants suppress the activation of airway muscles; surgical stress, pain, and environmental interference further deteriorate sleep quality. All these factors aggravate the pathophysiological changes in OSA patients and may lead to worse perioperative outcomes, including increased respiratory and cardiac events, intensive care unit (ICU) admission and delirium, as well as prolonged length of hospital stay.

Opioids are commonly used for postoperative analgesia. Patients with OSA have significantly increased sensitivity to the side effects of opioids, such as central respiratory depression (reduced central respiratory drive) and peripheral respiratory depression (airway collapse). Opioids themselves can also cause sleep disturbances, as manifested by sleep fragmentation, decreased rapid-eye-movement sleep, and frequent nightmares. On the other hand, sleep deprivations can also lead to increased pain sensitivity and thus opioid consumption. Therefore, it is important to explore better postoperative analgesia to improve postoperative sleep quality of patients at high-risk of OSA.

Dexmedetomidine is a highly selective α2-adrenergic agonist with sedative, analgesic, and anxiolytic effects. It produces sedation by activating the endogenous sleep-promoting pathway and produces a state resembling nonrapid eye movement sleep. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. When given in sub-anaesthetic doses, ketamine produces analgesic and anti-hyperalgesic effects and is recommended as a component of multimodal analgesia. Esketamine is the S-enantiomer of racemic ketamine and approximately twice as potent as racemic ketamine for analgesia.

A recent trial showed that mini-dose esketamine-dexmedetomidine in combination with opioids improved analgesia and subjective sleep quality after scoliosis correction surgery. This trial is designed to test the hypothesis that mini-dose dexmedetomidine-esketamine supplemented analgesia may improve sleep quality in patients at high-risk of OSA after thoracic or abdominal surgery.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100034

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. Aged ≥18 years but ≤80 years;
  2. Preoperative diagnosis of OSA, or judged to be at moderate-to-high risk of OSA according to the STOP-Bang Questionnaire;
  3. Scheduled to undergo thoracoscopic or laparoscopic surgery under general anesthesia, with an expected surgical duration of ≥1 hours, and required patient-controlled intravenous analgesia (PCIA) after surgery.

Exclusion criteria:

  1. Diagnosed as central sleep apnea syndrome;
  2. Previous history of schizophrenia, epilepsy, Parkinson disease, or myasthenia gravis.
  3. History of schizophrenia, or having antipsychotic drugs (including antidepressants or anxiolytics);
  4. Inability to communicate in the preoperative period because of coma, profound dementia, or deafness;
  5. History of drug or alcohol dependence, or sedative or hypnotic therapy within 1 month before surgery;
  6. Contraindications to ketamine (such as hyperthyroidism, pheochromocytoma, or glaucoma);
  7. Sick sinus syndrome, severe sinus bradycardia (<50 beats per minute), or second-degree or above atrioventricular block without pacemaker;
  8. Contraindications to high-flow nasal cannula therapy (such as mediastinal emphysema, shock or hypotension, cerebrospinal fluid leakage, nasosinusitis, otitis media, or deviation of nasal septum);
  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%), or ASA classification IV or above;
  10. Expected intensive care unit (ICU) admission with tracheal intubation after surgery;
  11. Other conditions that are considered unsuitable for study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dexmedetomidine-esketamine combination
Patient-controlled analgesia is established with dexmedetomidine (1 μg/ml), esketamine (1 mg/ml), and sufentanil (1 μg/ml) in a total volume of 100 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 but no more than 48 hours after surgery.
Drug: Dexmedetomidine-esketamine combination
Patient-controlled analgesia is established with dexmedetomidine (1 μg/ml), esketamine (1 mg/ml), and sufentanil (1 μg/ml) in a total volume of 100 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 but no more than 48 hours after surgery.
Other Names:
  • Dexmedetomidine-esketamine group
Placebo Comparator: Placebo
Patient-controlled analgesia is established with sufentanil (1 μg/ml) in a total volume of 100 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 but no more than 48 hours after surgery.
Drug: Placebo
Patient-controlled analgesia is established with sufentanil (1 μg/ml) in a total volume of 100 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 but no more than 48 hours after surgery.
Other Names:
  • Placebo group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective sleep quality during the first night after surgery.
Time Frame: During the first night after surgery.
Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure of subjective sleep quality with 5 items, including sleep depth, sleep latency, awakening, return to sleep, and overall sleep quality; the score of each item ranges from 0 to 100, with a higher score indicating better sleep.
During the first night after surgery.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sleep structure parameters during the first night after surgery.
Time Frame: During the first night after surgery
Sleep structure is monitored with a polysomnograph from 9:00 pm on the night of surgery to 6:00 am the next morning. Sleep stages and respiratory events are scored according to the American Academy of Sleep Medicine (AASM) manual by qualified sleep physicians.
During the first night after surgery
Cumulative subjective sleep quality score after surgery
Time Frame: During the first three nights after surgery.
Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). The RCSQ is a self-reported measure of subjective sleep quality with 5 items, including sleep depth, sleep latency, awakening, return to sleep, and overall sleep quality; the score of each item ranges from 0 to 100, with a higher score indicating better sleep.
During the first three nights after surgery.
Proportion of patients with poor sleep quality after surgery.
Time Frame: During the first three nights after surgery.
Subjective sleep quality is assessed with the Richards-Campbell Sleep Questionnaire (RCSQ). Poor sleep quality is defined as overall RCSQ<50 on any night after surgery.
During the first three nights after surgery.
Area under curve of pain intensity score within 3 days after surgery.
Time Frame: Up to 3 days after surgery.
Pain intensity is assessed twice daily (8-10 am and 18-20 pm) with the numeric rating scale (NRS), an 11-point scale where 0=no pain and 10=the worst pain.
Up to 3 days after surgery.
Subjective sleep quality at 30 days after surgery.
Time Frame: At 30 days after surgery.
Subjective sleep quality is assessed with the Pittsburgh Sleep Quality Index (PSQI; score ranges from 0 to 21, with higher score indicating worse sleep quality).
At 30 days after surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay in hospital after surgery.
Time Frame: Up to 30 days after surgery.
Length of stay in hospital after surgery.
Up to 30 days after surgery.
Sedation level within 3 days after surgery.
Time Frame: Up to 3 days after surgery.
Sedation level is assessed at 2 hours and twice daily (8-10 am and 18-20 pm) after surgery with the Richmond Agitation Sedation Scale (RASS), with scores ranging from -5(unarousable) to +4 (combative) and 0 indicates alert and calm.
Up to 3 days after surgery.
Incidence of delayed neurocognitive recovery.
Time Frame: At 30 days after surgery.
Cognitive function is assessed with the Telephone Montreal Cognitive Assessment (T-MoCA; scores range from 0 to 22, with higher score indicating better function) before surgery and at 30 days after surgery. A T-MoCA score reduction of 1 standard deviation (SD) or more from baseline is defined the occurrence of delayed neurocognitive recovery.
At 30 days after surgery.
Incidence of major complications after surgery.
Time Frame: Up to 30 days after surgery.
Major complications are defined as new-onset medical events that are deemed harmful and require therapeutic intervention, that is grade II or higher on the Clavien-Dindo classification.
Up to 30 days after surgery.
All-cause 30-day mortality.
Time Frame: Up to 30 days after surgery.
All-cause 30-day mortality.
Up to 30 days after surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Investigators

  • Principal Investigator: Dong-Xin Wang, M.D., Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2024

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

August 20, 2024

First Submitted That Met QC Criteria

August 20, 2024

First Posted (Actual)

August 22, 2024

Study Record Updates

Last Update Posted (Actual)

September 25, 2024

Last Update Submitted That Met QC Criteria

September 23, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-234

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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