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

Dexmedetomidine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06062550
• Other study ID #: 2023-351
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 2023
• Est. completion date: December 2026

Study information

• Verified date: October 2023
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD, PhD
• Phone: 8610-83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 312
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Postsurgical Pain
• Dexmedetomidine
• Esketamine
• Pain, Postoperative
• Postoperative Analgesia
• Scoliosis
• Scoliosis Correction

Intervention

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

Locations

Country	Name	City	State
China	Beijing University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (28)

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* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Agitation and sedation score at various timepoints 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).	Up to the 5th day after surgery.
Other	Incidence of postoperative delirium within the first 5 days.	Delirium is assessed with the Three-dimensional Confusion Assessment Method (3D-CAM) twice daily (8:00-10:00 and 18:00-20:00).	Up to the 5th day after surgery.
Other	Depression severity at 7 days 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.	At the 7th day after surgery.
Other	Length of stay in hospital after surgery.	Length of stay in hospital after surgery.	Up to 30 days after surgery.
Other	Incidence of postoperative complications within 30 days	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).	Up to 30 days after surgery.
Primary	Pain intensity with movement and opioid consumption within 72 hours.	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.	Within 72 hours after surgery
Secondary	Proportion of patients with moderate to severe pain within 72 hours.	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.	Up to 72 hours after surgery.
Secondary	The highest NRS pain score within 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.	Up to 72 hours after surgery.
Secondary	Area under curve of NRS pain score within 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.	Up to 72 hours after surgery
Secondary	Cumulative opioid consumption within 72 hours after surgery.	Cumulative opioid consumption within 72 hours after surgery.	Up to 72 hours after surgery
Secondary	Requirement of supplement analgesia within 72 hours.	Requirement of supplement analgesia within 72 hours.	Up to 72 hours after surgery
Secondary	Pain intensity at rest and opioid consumption within 72 hours.	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.	Within 72 hours after surgery.
Secondary	Subjective sleep quality during the first 5 postoperative days.	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).	Up to the 5th day after surgery.
Secondary	Number of days requiring analgesics within 30 days after surgery.	Number of days requiring analgesics within 30 days after surgery.	Up to 30 days after surgery.