Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery

Efficacy of Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery: A Randomized, Double-blind Trial

Scoliosis correction surgery is associated with severe pain. Patients after scoliosis correction surgery usually require high dose opioids and long duration analgesia, which may increase side effects and drug tolerance. In a recent trial, mini-dose esketamine and dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after spinal correction surgery without increasing adverse events; however, the proportion of patients with moderate-to-severe pain remained high. The authors speculate that increasing esketamine dose in the combination may further improve analgesic effects.

Spinal surgery is associated with severe pain, with a median pain score of 7 (interquartile range, 4 to 8) on the first postoperative day, and requires long duration analgesia. The total dose of opioids required for postoperative analgesia is about 2-4 times that for other surgeries. However, despite high dose opioids, the analgesic effects remain unsatisfied. In a recent trial of 200 patients following scoliosis correction surgery, the proportion with moderate-to-severe pain in patients given routine analgesia was 84.6%. Severe acute pain is an important risk factor of chronic postsurgical pain and is associated with an increased risk of long-term opioid use.

Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist. Low-dose ketamine infusion is recommended for postoperative analgesia but may cause neuropsychiatric side effects. Esketamine is the S-enantiomer of racemic ketamine with approximately twice as potent as racemic ketamine in analgesia and less likely to produce side effects. Dexmedetomidine is a highly selective α2 receptor agonist and has anxiolytic, sedative, analgesic effects. When used as a supplement to opioid analgesia, dexmedetomidine improves analgesia and sleep quality but may produce sedation.

In a recent trial, mini-dose esketamine-dexmedetomidine combination as a supplement to sufentanil significantly improved analgesia and subjective sleep quality after scoliosis correction surgery; no significant adverse reactions were observed. However, the proportion of moderate-to-severe pain remained high (65.7%) in these patients, so further improvement is needed. The authors speculate that increasing esketamine dose in the esketamine-dexmedetomidine combination may further improve the analgesia. This study aims to explore the effects of different dose esketamine in the combination on acute and chronic pain in patients following spinal deformity surgery.

Inclusion Criteria:

• Aged ≥18 years and body weight ≥40 kg;
• Scheduled to undergo scoliosis correction with pedicle screw fixation;
• Required patient-controlled intravenous analgesia after surgery.

Exclusion Criteria:

• Preoperative sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), atrioventricular block grade II or above without pacemaker; or comorbid with congenital heart disease, arrhythmia, or other serious cardiovascular diseases with a cardiac function grade ≥III;
• Patients with moderate and severe obstructive sleep apnea diagnosed preoperatively or according to the STOP-Bang score；
• History of hyperthyroidism and pheochromocytoma;
• History of schizophrenia, epilepsy, myasthenia gravis, or delirium;
• Severe liver dysfunction (child Pugh grade C), severe renal dysfunction (preoperative dialysis), or American Society of Anesthesiologists grade ≥IV;
• Barrier in communication;
• Other conditions that are considered unsuitable for study participation.