impact of frailty on nalbuphine dose for postoperative analgesia in elderly patients undergoing laparoscopic gi surgery

Conditions: PCIA; Frailty; Laparoscopic Gastrointestinal Surgery

Summary: this study aims to investigate the ed50 and ed95 of nalbuphine combined with dexmedetomidine in patient-controlled intravenous analgesia (pcia) for elderly patients with different degrees of frailty, as well as their analgesic effects and complications. the results of this study can provide safe and effective dosage guidance for postoperative analgesia in frail patients, help optimize analgesic regimens, reduce the risk of complications, and improve the quality of postoperative recovery.

with the increasing aging of the population in china, the proportion of elderly patients in the surgical population is continuously rising, with elderly frail patients accounting for as high as 25-50%. previous studies have shown that postoperative pain management in elderly frail patients is associated with four major issues: 1. enhanced pain perception. 2. decreased pain tolerance. 3. changes in pharmacokinetics and pharmacodynamics. 4. iatrogenic titration patterns. patient-controlled intravenous analgesia (pcia) is one of the most commonly used analgesic methods, which can shorten hospital stays, reduce the incidence of perioperative complications, and improve quality of life. however, elderly patients are more prone to hypotension, nausea, and vomiting, necessitating additional antiemetics and rescue analgesics. nalbuphine, a dual-acting drug as a κ-receptor agonist and μ-receptor antagonist, has analgesic potency comparable to morphine and a longer duration of action (3-6 hours). however, studies have shown that due to reduced liver and kidney function, the metabolism of nalbuphine is prolonged in elderly frail patients. dexmedetomidine, a highly selective α2-receptor agonist with sedative, analgesic, anxiolytic, and sympatholytic properties, can reduce postoperative cardiovascular complications, enhance opioid analgesia, and lower the incidence of postoperative delirium, making it an ideal choice for multimodal analgesia. however, no studies have yet explored the dose-response relationship of dexmedetomidine combined with nalbuphine in elderly frail patients, especially the impact of different degrees of frailty (such as mfi classification) on the median effective dose (ed50) of nalbuphine. this study, for the first time, employs the modified dixon up-and-down sequential method to systematically evaluate the influence of different degrees of frailty on the ed50 of nalbuphine-dexmedetomidine combination analgesia in elderly patients undergoing laparoscopic gastrointestinal surgery, and to analyze its analgesic effects and complication risks. the results of this study will provide evidence-based guidance for precise pain management in frail patients and promote the application of enhanced recovery after surgery (eras) principles in the elderly frail population.

Eligibility criteria:
inclusion criteria: 1. patients who plan to undergo elective gastrointestinal surgery and are expected to stay in hospital for ≥3 days after surgery \[except abdominal perineal combined with radical resection of rectal cancer (miles)\]; 2. asa grade i-ⅳ; 3. age ≥65 years (2); 4. 18.5 kg/m²≤bmi\<30 kg/m²; 5. sign the informed consent form. exclusion criteria: 1. severe cardiopulmonary, liver, kidney and coagulation dysfunction 2. chemotherapy and radiotherapy were administered 1 month before surgery, and sedatives, antiemetic or antipruritic drugs were administered 24 hours before surgery 3. history of drug abuse, chronic pain, mental illness, or allergy to the drugs used in this study 4. plan postoperative intubation or transfer to icu; 5. participated in other clinical studies within the past 3 months.

Keywords: nalbuphine ed50 pcia laparoscopic gastrointestinal surgery frailty