The Effect of Esketamine Combined With Pregabalin on Chronic Postsurgical Pain in Patients After Craniotomy.

The Effect of Esketamine Combined With Pregabalin on Chronic Postsurgical Pain in Patients After Craniotomy.

The Effect of Esketamine Combined With Pregabalin on Chronic Postsurgical Pain in Patients After Craniotomy.

Chronic postsurgical pain (CPSP), which is one of the most common and serious long term complication of surgery，occurs in approximately 10% of patients after a surgical procedure. Craniotomy was previously considered to have less chronic pain than other surgical procedures. Contrarily, studies have reported incidences of chronic headache varies for type of craniotomy, ranging from 23% to 34% at three months and 12% to 16% at one year after surgery. In addition，CPSP is associated with adverse events, including postoperative morbidity, increased health-care costs, significant impaired on quality of life, prolonged opioid use. Optimising perioperative pain management should reduce the incidence of CPSP; The non-opioid analgesics, such as ketamine and pregabalin, have also been used as components of multimodal anesthetic protocols. Postoperative pain scores and opioid use are significantly reduced in thoracotomy surgical patients given ketamine and pregabalin compared to control groups.however, there is currently a lack of evidence regarding which therapeutic options are most effective in reducing the incidence of chronic post-craniotomy headache. The investigators hypothesis is that sketamine combined with pregabalin reduces significantly chronic postoperative pain after craniotomy and improves patient outcome.

Drug: S-ketamine and pregabalin Drug: Pregabalin 150mg (2hrs) pre operatively and 75mg twice daily post operatively for 7 days(POD1-7),followed by dose reduction to 75mg once daily for 7days(POD8-14) Drug: S-ketamine infusion 0.5 mg/kg bolus after induction of anesthesia +0.12 mg/kg/h continuous intravenous infusion for 48 h

Drug: Normal saline and placebo capsule Drug: Placebo capsules :Two placebo capsules(2hrs) preoperatively and twice daily post operatively for 7days, followed by dose reduction to single capsule once daily for 7days Drug: Normal saline• 0.9% saline bolus after induction of anesthesia +intravenous infusion for 48 hours

S-ketamine and pregabalin Drug: Pregabalin • 150mg (2hrs) pre operatively and 75mg twice daily post operatively for 7 days(POD1-7),followed by dose reduction to 75mg once daily for 7days(POD8-14) Drug: S-ketamine infusion • 0.5 mg/kg bolus after induction of anesthesia +0.12 mg/kg/h continuous intravenous infusion for 48 h

Inclusion Criteria: Adults, age ≥18 years, male or female American Society of Anaesthesiology (ASA) status I-III Patients undergoing elective craniotomy Exclusion Criteria: Patients unable to complete scale assessment Pregnant or lactating women Patients with preoperative chronic pain syndrome Patients with previous craniotomy history Patients with a history of mental illness who are receiving medication Patients with liver and kidney dysfunction Patients have taken pain medication within two weeks Patients with history of adverse reactions to pregabalin, ketamine and esticketamine Patients with history of drug abuse; BMI>35.0 kg · m - 2.