Clinical trial NCT06953570: Impact of Frailty on Nalbuphine Dose for Postoperative Analgesia in Elderly Patients Undergoing Laparoscopic GI Surgery
Official title: Impact of Frailty on the Median Effective Dose of Nalbuphine in Patient-Controlled Intravenous Analgesia for Postoperative Pain in Elderly Patients Undergoing Laparoscopic Gastrointestinal Surgery: A Prospective, Double-Blind, Cohort Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: PCIA
Frailty
Laparoscopic Gastrointestinal Surgery
Keywords: nalbuphine
ED50
PCIA
laparoscopic gastrointestinal surgery
frailty
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
First posted: 2025-05-01
Enrollment: 120
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Elderly patients undergoing laparoscopic gastrointestinal surgery

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Median Effective Dose (ED50) of Nalbuphine Based on Visual Analogue Scale (VAS) for Resting Pain at 24 Hours After Surgery
timeFrame: Within 24 hours after the end of surgery
Secondary outcomes:
measure: Dose of Nalbuphine Required to Achieve Resting VAS ≤3 in 95% of Patients Within 24 Hours After Surgery (ED95)
timeFrame: Within 24 hours after the end of surgery
measure: Resting/Moving VAS (VASR/ VASM)
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Ramsay Sedation Score (RASS)
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Brinell comfort Scale (BCS)
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Nausea and vomiting (PONV)
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: the effective pressing number of PCIA
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: the cumulative pressing number of PCIA
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: sufentanil dose
timeFrame: Exiting PACU immediately
measure: Time to recovery
timeFrame: Exiting PACU immediately
measure: Postoperative Functional Recovery Milestones at Hospital Discharge
timeFrame: At hospital discharge, typically within 3 to 7 days after surgery
measure: Rescue Analgesic Requirements Within 48 Hours After Surgery
timeFrame: At 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Systolic Blood Pressure (SBP) Within 48 Hours After Surgery
timeFrame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
measure: Number of Participants Experiencing Respiratory Depression (RR <8/min or SpO₂ ≤90%) After Surgery
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Number of Participants Requiring Antipruritic Medication for Persistent Itching After Surgery
timeFrame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
measure: Diastolic Blood Pressure (DBP) Within 48 Hours After Surgery
timeFrame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
measure: Mean Arterial Pressure (MAP) Within 48 Hours After Surgery
timeFrame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
measure: Heart Rate (HR) Within 48 Hours After Surgery
timeFrame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
measure: Peripheral Oxygen Saturation (SpO₂) Within 48 Hours After Surgery
timeFrame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
name: Yongtao Sun, Ph.D.
role: STUDY_CHAIR
References:
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