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

Sponsor

Peking University First Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06062550

Collaborator

(none)

312

Enrollment

Location

Arms

Anticipated Duration (Months)

8.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Scoliosis Correction Esketamine Dexmedetomidine Postoperative Analgesia Chronic Postsurgical Pain	Drug: Esketamine	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

312 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Low-dose group Patient-controlled analgesia is established with esketamine 50 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.	Drug: Esketamine Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.
Experimental: Medium-dose group Patient-controlled analgesia is established with esketamine 100 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.	Drug: Esketamine Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.
Experimental: High-dose group Patient-controlled analgesia is established with esketamine 150 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.	Drug: Esketamine Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.

Arm

Intervention/Treatment

Active Comparator: Low-dose group

Patient-controlled analgesia is established with esketamine 50 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.

Drug: Esketamine

Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.

Experimental: Medium-dose group

Patient-controlled analgesia is established with esketamine 100 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.

Drug: Esketamine

Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.

Experimental: High-dose group

Patient-controlled analgesia is established with esketamine 150 mg, dexmedetomidine 200 microgram, and sufentanil 4 microgram/kg (maximum 250 microgram), diluted with normal saline to 200 ml, and programmed to administer 2-ml boluses with a lockout interval of 8 minutes and a background infusion rate at 1 ml/h.

Drug: Esketamine

Different doses of esketamine in the esketamine-dexmedetomidine combination as a supplement to sufentanil for postoperative intravenous analgesia.

Outcome Measures

Primary Outcome Measures

Pain intensity with movement and opioid consumption within 72 hours. [Within 72 hours after surgery]
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed area under curve (AUC) and opioid consumption (OC) compared to the all patients.

Secondary Outcome Measures

Proportion of patients with moderate to severe pain within 72 hours. [Up to 72 hours after surgery.]
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement. Moderate to severe pain is defined as any NRS pain score of 4 or higher.
The highest NRS pain score within 72 hours after surgery. [Up to 72 hours after surgery.]
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Area under curve of NRS pain score within 72 hours after surgery. [Up to 72 hours after surgery]
Pain intensity is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = no pain and 10 = the worst pain) twice daily (8:00-10:00 and 18:00-20:00) at rest and with movement.
Cumulative opioid consumption within 72 hours after surgery. [Up to 72 hours after surgery]
Cumulative opioid consumption within 72 hours after surgery.
Requirement of supplement analgesia within 72 hours. [Up to 72 hours after surgery]
Requirement of supplement analgesia within 72 hours.
Pain intensity at rest and opioid consumption within 72 hours. [Within 72 hours after surgery.]
A comprehensive index of pain intensity and opioid consumption is calculated. The range of the index is -200% to +200%; values above 0 indicate increased summed AUC and OC compared to the all patients.
Subjective sleep quality during the first 5 postoperative days. [Up to the 5th day after surgery.]
Subjective sleep quality is evaluated with the Numeric Rating Scale (NRS, an 11-point scale where 0 = the best sleep and 10 = no sleep at all) once daily (8:00-10:00).
Number of days requiring analgesics within 30 days after surgery. [Up to 30 days after surgery.]
Number of days requiring analgesics within 30 days after surgery.

Other Outcome Measures

Agitation and sedation score at various timepoints after surgery. [Up to the 5th day after surgery.]
Agitation and sedation score is evaluated with the Richmond Agitation and Sedation Scale (RASS, with scores ranging from -5 [unarousable] to +4 [combative] and 0 indicates alert and calm) twice daily (8:00-10:00 and 18:00-20:00).
Incidence of postoperative delirium within the first 5 days. [Up to the 5th day after surgery.]
Delirium is assessed with the Three-dimensional Confusion Assessment Method (3D-CAM) twice daily (8:00-10:00 and 18:00-20:00).
Depression severity at 7 days after surgery. [At the 7th day after surgery.]
Depression is assessed with the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 includes 9-item requiring responses of 0 (not at all) to 3 (nearly every day) to assess the occurrence of depressive symptoms over the last two weeks. It has 8 items on depressive symptoms and 1 focused on suicidal ideation. Total scores range from 0 to 27, with higher score indicating more severe symptoms.
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 defined as new-onset medical conditions that were deemed harmful and required therapeutic intervention (i.e., grade II or higher on the Clavien-Dindo classification).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.