Impact of Frailty on Nalbuphine Dose for Postoperative Analgesia in Elderly Patients Undergoing Laparoscopic GI Surgery

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.

• Dose of Nalbuphine Required to Achieve Resting VAS ≤3 in 95% of Patients Within 24 Hours After Surgery (ED95) [Срок оценки: Within 24 hours after the end of surgery]
• Resting/Moving VAS (VASR/ VASM) [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• Ramsay Sedation Score (RASS) [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• Brinell comfort Scale (BCS) [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• Nausea and vomiting (PONV) [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• the effective pressing number of PCIA [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• the cumulative pressing number of PCIA [Срок оценки: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• sufentanil dose [Срок оценки: Exiting PACU immediately]
• Time to recovery [Срок оценки: Exiting PACU immediately]
• Postoperative Functional Recovery Milestones at Hospital Discharge [Срок оценки: At hospital discharge, typically within 3 to 7 days after surgery]
• Rescue Analgesic Requirements Within 48 Hours After Surgery [Срок оценки: At 6, 12, 18, 24, 36, and 48 hours after the end of surgery]
• Systolic Blood Pressure (SBP) Within 48 Hours After Surgery [Срок оценки: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery]