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.
Study Type
OBSERVATIONAL
Enrollment
120
Median Effective Dose (ED50) of Nalbuphine Based on Visual Analogue Scale (VAS) for Resting Pain at 24 Hours After Surgery
The median effective dose (ED50) of nalbuphine is defined as the dose at which 50% of patients report a resting Visual Analogue Scale (VAS) pain score of ≤3 within 24 hours postoperatively. The VAS is a 10-cm line scale ranging from 0 (no pain) to 10 (worst imaginable pain), evaluated at rest.
Time frame: Within 24 hours after the end of surgery
Dose of Nalbuphine Required to Achieve Resting VAS ≤3 in 95% of Patients Within 24 Hours After Surgery (ED95)
The 95% effective dose (ED95) of nalbuphine is defined as the dose at which 95% of patients report a resting pain score of ≤3 on the Visual Analogue Scale (VAS) within 24 hours after laparoscopic gastrointestinal surgery. The VAS is a 10-cm horizontal line scale from 0 (no pain) to 10 (worst pain imaginable), evaluated in a supine resting state
Time frame: Within 24 hours after the end of surgery
Resting/Moving VAS (VASR/ VASM)
The VAS is assessed at rest and during moving (coughing or changing position from back to side in bed). The pain degree was assessed with a 10cm scale (0-10 points) : 0 was no pain; A score below 3 indicates mild pain, which the patient can tolerate; 4-6 patients pain and affect sleep, can still tolerate; 7-10 points patients have gradually intense pain, the pain is unbearable.
Time frame: 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)
1 awake, patient anxious, restless or irritable; 2 points awake, patient cooperation, good orientation or quiet; At 3 points of wakefulness, the patient only responds to commands; 4 minutes sleep, patients respond quickly to tapping eyebrow or Johnson stimulation; 5 minutes sleep, the patient is slow to tap eyebrow or Johnson stimulation; 6 minutes of sleep, the person did not respond to tapping the eyebrow or Johnson stimulation.
Time frame: 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)
0 is persistent pain; 1 is painless at rest, severe pain when breathing deeply or coughing; 2 are painless at rest, mild pain when breathing deeply or coughing; There was no pain during 3 minutes of quiet and deep breathing. 4 points: No pain when coughing.
Time frame: 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)
Nausea is an uncomfortable feeling of wanting to vomit, but there is no contractive movement of the abdominal muscles, diaphragm muscles, etc. Vomiting refers to the contraction of the diaphragm, chest muscles and abdominal wall muscles, which may be accompanied by vomiting of stomach contents, including dry heaving. If the vomiting events are more than 1 minute apart, they are considered separate episodes. 0 degree indicates no nausea or vomiting. Grade I is nausea and no vomiting; Grade Ⅱ was nausea with mild vomiting; Degree III is severe vomiting requiring further treatment; Grade IV is vomiting that is difficult to control.
Time frame: 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
The effective number of PCIA compressions performed by the patient after surgery
Time frame: 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
The total number of postoperatively applied PCIA
Time frame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
sufentanil dose
rescue sufentanil doses in PACU
Time frame: Exiting PACU immediately
Time to recovery
length of stay in PACU
Time frame: Exiting PACU immediately
Postoperative Functional Recovery Milestones at Hospital Discharge
Functional recovery is defined as the ability of the patient to (1) independently get out of bed, (2) walk at least 10 meters with or without assistance, (3) tolerate oral intake (clear fluids or diet), and (4) urinate spontaneously. Recovery is assessed using a standardized checklist by the attending physician or nurse prior to discharge.
Time frame: At hospital discharge, typically within 3 to 7 days after surgery
Rescue Analgesic Requirements Within 48 Hours After Surgery
Number of additional doses of rescue analgesics administered to the patient within the first 48 hours postoperatively, recorded by nursing staff
Time frame: At 6, 12, 18, 24, 36, and 48 hours after the end of surgery
Systolic Blood Pressure (SBP) Within 48 Hours After Surgery
SBP will be measured using automated patient monitors at predefined time points. The values will be recorded and analyzed as a continuous variable.
Time frame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
Number of Participants Experiencing Respiratory Depression (RR <8/min or SpO₂ ≤90%) After Surgery
Respiratory depression is defined as a respiratory rate \<8 breaths per minute or an oxygen saturation (SpO₂) ≤90% on room air. The incidence will be recorded at each predefined time point by nursing staff using bedside monitors
Time frame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
Number of Participants Requiring Antipruritic Medication for Persistent Itching After Surgery
Pruritus is defined as persistent itching that leads to administration of antipruritic medication (e.g., antihistamines or corticosteroids). The number of participants requiring such medications at each time point will be recorded by medical staff.
Time frame: At PACU discharge (immediately after anesthesia recovery), and at 6, 12, 18, 24, 36, and 48 hours after the end of surgery
Diastolic Blood Pressure (DBP) Within 48 Hours After Surgery
DBP will be measured using automated patient monitors at predefined time points. The values will be recorded and analyzed as a continuous variable.
Time frame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
Mean Arterial Pressure (MAP) Within 48 Hours After Surgery
MAP will be measured using automated patient monitors at each specified time point. MAP is calculated using the formula: (SBP + 2 × DBP) / 3.
Time frame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
Heart Rate (HR) Within 48 Hours After Surgery
Heart rate will be measured using automated patient monitors. The values will be recorded in beats per minute (bpm) and analyzed continuously over time.
Time frame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
Peripheral Oxygen Saturation (SpO₂) Within 48 Hours After Surgery
SpO₂ will be recorded using pulse oximetry. Oxygen saturation (%) will be continuously monitored and recorded at predefined intervals.
Time frame: At PACU discharge, and at 6, 12, 18, 24, 36, and 48 hours after surgery
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