Clinical trial NCT06087510: Different Dose Esketamine and Dexmedetomidine for Supplemental Analgesia and Longterm Outcomes
Official title: Impact of Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia on Long-term Outcomes After Scoliosis Correction Surgery: Follow-up of a Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Scoliosis Correction
Postoperative Analgesia
Esketamine
Dexmedetomidine
Chronic Postsurgical Pain
Keywords: Scoliosis Correction
Postoperative analgesia
Esketamine
Dexmedetomidine
Chronic Postsurgical Pain
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2023-10-17
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Chronic postsurgical pain (CPSP) refers to pain that occurs or increases after surgery and lasts longer than 3 months. Severe acute postoperative pain is one of the major risk factors of CPSP. Spinal correction surgery is associated with severe pain due to large trauma and long duration. Ketamine and esketamine are N-methyl-D-aspartate receptor antagonists; they have antihyperalgesic effects and may reduce CPSP. Dexmedetomidine is an alpha 2-adrenoceptor agonist with sedative, anxiolytic, and analgesic effect; it is frequently used as an adjuvant to postoperative analgesia. In a previous trial of 200 patients after scoliosis correction surgery, mini-dose esketamine-dexmedetomidine in combination with opioids significantly improved analgesia and sleep quality but did not reduce CPSP. The authors speculate that increasing esketamine dose in the combination may further improve analgesia and, therefore, reduce the occurrence of CPSP.

Detailed description: Chronic postsurgical pain (CPSP) refers to pain that occurs or increases after surgery and lasts longer than 3 months. Pain can be limited to the surgical area or projected to the innervated area. The incidence of CPSP is reported from 10% to 50%, with incidence of moderate-to-severe CPSP of about 11.8%. Risk factors of CPSP include severe acute postoperative pain, long duration surgery, and related nerve injury. Spinal correction surgery is associated with severe acute postoperative pain due to large trauma and long duration, with a median pain score of 7 (interquartile range, 4 to 8) on the first day after surgery. And the incidence of persistent pain is up to 75%.

Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists. Ketamine has anti-hyperalgesia effects and may reduce the occurrence of CPSP by blocking NMDA receptors. Esketamine is the S-enantiomer of racemic ketamine with stronger analgesic effect and less adverse reactions. In previous studies, opioid-dependent patients who received low-dose ketamine/esketamine infusion during the perioperative period had decreased pain scores and opioid requirement at 6 weeks, 6 months, and 1 year after surgery. However, results in patients without opioid dependence are controversial.

Dexmedetomidine is a highly selective α2 receptor agonist with sedative, anxiolytic, and analgesic effects. When used in the perioperative period, dexmedetomidine improves analgesia, reduces opioid consumption, and decreases opioid-related adverse reactions. Meanwhile, dexmedetomidine can prolong total sleep time, improve sleep efficiency, and increase subjective sleep quality, possibly by activating the endogenous sleep-promoting pathway. The sedative effect of dexmedetomidine may help to reduce the psychiatric adverse reactions of ketamine. However, data is lacking regarding the effect of dexmedetomidine on chronic postsurgical pain.

In a previous trial of 200 patients following scoliosis correction surgery, mini-dose esketamine-dexmedetomidine in combination with opioids significantly improved analgesia and sleep quality after surgery but did not reduce CPSP. The authors speculate that increasing esketamine dose in the combination may further improve analgesia and, therefore, reduce the occurrence of CPSP.

Eligibility criteria: Inclusion Criteria:

* Patients aged ≥18 years and body weight≥40 kg;
* Scheduled to undergo scoliosis correction with pedicle screw fixation;
* Required patient-controlled intravenous analgesia (PCIA) after surgery.

Exclusion Criteria:

* Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate \<50 beats per minute), atrioventricular block grade II or above without pacemaker, congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a New York Heart Association class ≥III;
* Patients with moderate or severe obstructive sleep apnea diagnosed preoperatively or according to the STOP-Bang score;
* History of hyperthyroidism or pheochromocytoma;
* History of schizophrenia, epilepsy, myasthenia gravis;
* Severe liver dysfunction (Child-Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anaesthesiologists grade ≥IV;
* Barrier in communication;
* Other conditions that were considered unsuitable for study participation.

Primary outcomes:
measure: Incidence of chronic postsurgical pain at 3 months after surgery.
timeFrame: At 3 months after surgery.
Secondary outcomes:
measure: Incidence of chronic postsurgical pain at 6 or 12 months after surgery.
timeFrame: At 6 or 12 months after surgery.
measure: Severity of chronic pain at 3, 6, and 12 months after surgery.
timeFrame: At 3, 6, and 12 months after surgery.
measure: Proportion of chronic analgesic use after surgery.
timeFrame: At 3, 6, and 12 months after surgery.
measure: Subjective sleep quality at 3, 6, and 12 months after surgery.
timeFrame: At 3, 6, and 12 months after surgery.
measure: Severity of depression at 3, 6, and 12 months after surgery.
timeFrame: At 3, 6, and 12 months after surgery.
measure: Quality of life at 3, 6, and 12 months after surgery.
timeFrame: At 3, 6, and 12 months after surgery.
measure: Event-free survival.
timeFrame: Up to 12 months after surgery.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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