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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 312
- 试验地点
- 1
- 主要终点
- Incidence of chronic postsurgical pain at 3 months after surgery.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Esketamine (Drug)
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.
干预措施: Esketamine (Drug)
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.
干预措施: Esketamine (Drug)
结局指标
主要结局
Incidence of chronic postsurgical pain at 3 months after surgery.
时间窗: 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).
次要结局
- Incidence of chronic postsurgical pain at 6 or 12 months after surgery.(At 6 or 12 months after surgery.)
- Severity of chronic pain at 3, 6, and 12 months after surgery.(At 3, 6, and 12 months after surgery.)
- Proportion of chronic analgesic use after surgery.(At 3, 6, and 12 months after surgery.)
- Subjective sleep quality at 3, 6, and 12 months after surgery.(At 3, 6, and 12 months after surgery.)
- Severity of depression at 3, 6, and 12 months after surgery.(At 3, 6, and 12 months after surgery.)
- Quality of life at 3, 6, and 12 months after surgery.(At 3, 6, and 12 months after surgery.)
- Event-free survival.(Up to 12 months after surgery.)
研究者
Dong-Xin Wang
Professor and Chairman, Department of Anesthesiology
Peking University First Hospital