# Appropriate Combination of Nalbuphine Combined With Esketamine for Weakly Opioid Anesthesia in Postlaparoscopic Cholecystectomy Analgesia: A Randomized Controlled Trial

## TL;DR

This study finds that combining nalbuphine and esketamine improves pain relief and reduces side effects after laparoscopic cholecystectomy surgery.

## Contribution

The study identifies an optimal low-dose combination of nalbuphine and esketamine for postoperative pain management.

## Key findings

- Combining nalbuphine and esketamine significantly lowers pain scores compared to nalbuphine alone.
- The combination reduces the need for additional pain medication and adverse effects like vomiting.
- Higher esketamine doses increase sedation but also improve cognitive scores post-surgery.

## Abstract

Laparoscopic cholecystectomy (LC) often leads to abdominal wall incision pain, visceral pain, and shoulder and neck pain after surgery. Nalbuphine provides strong sedative and analgesic effects with minimal risk of adverse reactions. Esketamine, with its higher receptor affinity, significantly alleviates both visceral and somatic pain.

Our objective was to establish the optimal dosage of nalbuphine with esketamine for patient‐controlled intravenous analgesia (PCIA) following LC, enhancing postoperative pain management for these patients.

This research employs a single‐blind, randomized controlled trial methodology. Surgical patients were randomly assigned to three groups based on postoperative PCIA drug combinations: Group N received nalbuphine 2 mg·kg−1 with 100 mL of 0.9% sodium chloride solution; Group NE1 received esketamine 0.5 mg·kg−1, nalbuphine 2 mg·kg−1, and 100 mL of 0.9% sodium chloride solution; Group NE2 received esketamine 1 mg·kg−1, nalbuphine 2 mg·kg−1, and 100 mL of 0.9% sodium chloride solution. The study observed VAS scores at rest and during activity, Ramsay sedation scores, and MoCA scores at 6, 12, 24, and 48 h postsurgery, along with the total and effective PCIA pressing times across the three groups. Adverse reactions and the frequency of rescue analgesia within 48 h postsurgery were monitored.

Compared to the N group, VAS scores and resting pain scores were substantially lower in the NE1 and NE2 groups at 6 h, 12 h, and 24 h postsurgery (p < 0.05). Compared to Group N, Groups NE1 and NE2 had reduced postactivity VAS scores at 48 h postsurgery (p < 0.05). Compared to Group NE1, Group NE2 had reduced VAS scores at 12 h and 24 h following surgery (p < 0.05). Compared with Group N, the Ramsay sedation scores were higher in Group NE1 and Group NE2 at 6 h, 12 h, and 24 h following surgery (p < 0.05). Compared with Group NE1, Group NE2 had higher Ramsay sedation scores at 6 h and 12 h postoperatively (p < 0.05). The total number of analgesic pump presses and the number of effective presses in the NE1 and NE2 groups were substantially lower than those in the N group (p < 0.05). Compared with the NE1 group, the total number of presses and the number of effective presses in the NE2 group were reduced at 24 h and 48 h postoperatively (p < 0.05). Compared with Group N, the cognitive scores on the MoCA scale were markedly increased in Group NE1 and Group NE2 at 6 h, 12 h, and 24 h postoperatively (p  < 0.05). The incidence of vomiting was substantially lower in the NE1 and NE2 groups than in the N group at 48 h postoperatively (p < 0.05). The rate of drowsiness was markedly increased in the NE2 group than in the N and NE1 groups during the 48 h postoperative period (p < 0.05).

The combination of nalbuphine (2 mg kg−1) and esketamine (0.5 mg kg−1) effectively relieves postsurgical pain, reduces the incidence of postoperative PCIA use, and lowers the incidence of adverse events after LC.

ClinicalTrials.gov identifier: ChiCTR2400088373