Different Dose Esketamine and Dexmedetomidine for Supplemental Analgesia and Longterm Outcomes

Dexmedetomidine Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06087510
• Other study ID #: 2023-351-2
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 2024
• 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

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.

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.

Recruitment information / eligibility

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

Eligibility

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.

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 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
Primary	Incidence of chronic postsurgical pain at 3 months after surgery.	Chronic postsurgical pain (CPSP) is defined as pain persisted for at least three months after surgery, that is not present before surgery or that has different characteristics, and other possible causes of the pain are excluded (e.g., cancer recurrence, infection).	At 3 months after surgery.
Secondary	Incidence of chronic postsurgical pain at 6 or 12 months after surgery.	Chronic postsurgical pain (CPSP) is defined as pain persisted for at least three months after surgery, that is not present before surgery or that has different characteristics, and other possible causes of the pain are excluded (e.g., cancer recurrence, infection).	At 6 or 12 months after surgery.
Secondary	Severity of chronic pain at 3, 6, and 12 months after surgery.	Severity of chronic pain is assessed with the Brief Pain Inventory (BPI). The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score is calculated from the four items about pain intensity. Each item is rated from 0, no pain, to 10, pain as bad as you can imagine, and contributes with the same weight to the final score, ranging from 0 to 40.	At 3, 6, and 12 months after surgery.
Secondary	Proportion of chronic analgesic use after surgery.	Chronic analgesic use is defined as consecutive use of analgesics for more than 3 months.	At 3, 6, and 12 months after surgery.
Secondary	Subjective sleep quality at 3, 6, and 12 months after surgery.	Subjective sleep quality is assessed with the Pittsburgh Sleep Quality Index (PSQI). The PSQI is a 7-item questionnaire consisting 19 self-rated questions that assesses sleep quality over the last month, each weighted equally on a 0-3 scale; higher scores indicate worse sleep quality.	At 3, 6, and 12 months after surgery.
Secondary	Severity of depression at 3, 6, and 12 months 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 3, 6, and 12 months after surgery.
Secondary	Quality of life at 3, 6, and 12 months after surgery.	Quality of life is assessed using the Scoliosis Research Society-22 (SRS-22) patient questionnaire, which consists of five domains: function, pain, mental health, self-image, and satisfaction with management. Each domain has five questions except the last, which has two. The total score for each item ranges from 1 to 5, with 5 being the best. Each domain has a total sum score ranging from 5 to 25, except for the satisfaction domain, which ranges from 2 to 10. Results are expressed as the mean (total sum of the domain divided by the number of items answered) for each domain.	At 3, 6, and 12 months after surgery.
Secondary	Event-free survival.	Event indicates any condition that requires hospitalization and clinical treatment for unexpected reasons.	Up to 12 months after surgery.