Effect of Esketamine and Lidocaine on Postoperative Chronic Pain and Long-term Survival in Patients Undergoing Hepatectomy

This study is a further observation and follow-up of the patients enrolled in the registration number ChiCTR230007164430 to further evaluate the effect of long term infusion of esketamine and lidocaine on postoperative chronic pain, long-term quality of life and survival rate in patients undergoing hepatectomy. 304 patients with primary liver cancer who meet the inclusion criteria were included. According to the random number, the patients were divided into esketamine-lidocaine group and conventional analgesia group. In the esketamine-lidocaine group, patients received esketamine (0.25 mg/kg) and lidocaine (1.5 mg/kg) at the induction of anesthesia, followed by the continuous infusion of esketamine (0.02 mg/kg∙h) and lidocaine (1.5 mg/kg∙h) until the end of surgery. Postoperatively, the patients used 2 pumps. One pump delivered a fixed-rate infusion of lidocaine at 1.0 mg.kg-1.h-1 and esketamine at 0.02 mg.kg-1.h-1 infusion for 72 hours. Another PCIA device contained sufentanil 2 ug/kg, granisetron 12 mg diluted to 200 mL in 0.9 % normal saline. In the placebo group, the same volume of normal saline instead of lidocaine and esketamine will be administered. Numeric rating scale (NRS) is used to evaluate pain at rest and light activities at postoperative 24, 48, 72 hours. Follow-up after discharge includes chronic pain, the impact of chronic pain on quality of life, the relapse-free survival and overall survival from postoperative 3 months to 5 years.

Inclusion criteria

• Aged 18-75 years;
• Scheduled for elective hepatectomy;
• ASA grade I-III.

Exclusion criteria

• Patients who have been intubated in the ICU following surgery and do not have a planned extubation within 6 hours postoperatively.
• Patients with a body weight less than 40 kg or greater than 100 kg.
• Patients with cardiac conduction system abnormalities (second- or third-degree atrioventricular block) or cardiac insufficiency (left ventricular ejection fraction < 50%).
• Patients with severe hepatic insufficiency (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or bilirubin levels more than 2.5 times the upper limit of normal) or renal insufficiency (creatinine clearance rate < 60 mL/min).
• Patients with a known hypersensitivity to the investigational drug.
• Patients with a history of long-term opioid abuse.
• Patients who are unable to communicate effectively.
• Patients with serious comorbid medical conditions, such as uncontrolled hypertension, coronary heart disease, intracranial vascular malformations, or acute asthma exacerbations.
• Patients with a history of epilepsy or a history of manic episodes.
• Pregnant or breastfeeding women.
• Patients with glaucoma.
• Patients with preoperative cognitive dysfunction, bipolar disorder, or other psychiatric disorders, including mental retardation.
• Patients with primary liver cancer in conjunction with malignant tumors of other organs (such as lung, kidney, intestine, etc.), or those with clinical symptoms or imaging findings suggestive of distant metastasis.