Preemptive Nalbuphine Attenuates Remifentanil-Induced Postoperative Hyperalgesia After Laparoscopic Cholecystectomy: A Prospective Randomized Double-Blind Clinical Trial

BACKGROUND: Remifentanil-induced hyperalgesia (RIH) is a paradoxical phenomenon that may increase sensitivity to painful stimuli. Nalbuphine, which is both a μ-receptor antagonist and κ-receptor agonist, may affect RIH. The aim of this study was to evaluate the effects of nalbuphine on RIH during laparoscopic cholecystectomy. METHODS: A total of 96 patients were divided into the following four groups: 0.4 μg/kg/min of remifentanil with 0.2 mg/kg of nalbuphine (HRNA), 0.4 μg/kg/min of remifentanil with saline (HRSA), 0.1 μg/kg/min of remifentanil with 0.2 mg/kg of nalbuphine (LRNA), and 0.1 μg/kg/min of remifentanil with saline (LRSA). The pain thresholds of postoperative mechanical hyperalgesia were measured with von Frey filaments. Pain intensity and analgesic consumption were recorded up to 48 h after surgery. RESULTS: Pain thresholds on the inner forearm decreased in the HRSA group compared with the HRNA (P = 0.0167), LRNA (P = 0.0027), and LRSA (P = 0.0318) groups at 24 h after surgery. Pain thresholds on the peri-incisional area decreased in the HRSA group compared with HRNA, LRNA, and LRSA (all P < 0.0001) groups at 24 h after surgery. Patients in the HRNA group showed lower numeric rating scale scores at 1 h (P = 0.0159), 3 h (P = 0.0118), 6 h (P = 0.0213), and 12 h (P = 0.0118) than those in the HRSA group. Postoperative requirement for sufentanil was greater in the HRSA group than the HRNA group during the first 3 h (P = 0.0321) and second 3 h (P = 0.0040). Postoperative sufentanil consumption was also greater in the LRSA group than in the LRNA group during the first 3 h (P = 0.0321) and second 3 h (P = 0.0416). CONCLUSION: Preemptive nalbuphine can ameliorate postoperative hyperalgesia induced by high-dose remifentanil in patients undergoing laparoscopic cholecystectomy.