Evaluation of the Efficacy of Low-Dose Naloxone for the Prevention of Acute Remifentanil-Induced Hyperalgesia in Patients Undergoing General Anesthesia for Laparotomy

Background: Hyperalgesia is a major complication of continuous or intermittent opioid administration. The evidence suggests that concomitant administration of low-dose naloxone could prevent the development of acute opioid-induced hyperalgesia, with no effect on pain control. Objectives: The current study aimed to assess the effects of intraoperative low-dose naloxone, adding to remifentanil infusion on preventing acute postoperative hyperalgesia in patients undergoing general anesthesia for laparotomy. Methods: In this randomized clinical trial, patients undergoing general anesthesia for laparotomic hysterectomy in a tertiary referral teaching hospital from February to December 2019 were randomly assigned to one of three groups of remifentanilnaloxone (remifentanil 0.3 mu g/kg/min with low-dose naloxone 0.25 mu g/kg /h prepared in 50 mL of normal saline), remifentanil (0.3 mu g/kg/min), and control (receiving 50 mL saline infusion), intraoperatively. Patients and researchers were blinded to the type of intervention. The severity of hyperalgesia, as the main outcome, was evaluated by the static Tactile test. The severity of pain was assessed by visual analogous scale 0.5, 2, 6,12, and 24 hours after surgery. Results: In total, 75 patients were evaluated. The results showed no difference concerning the independent variables (age, body mass index, hypertension, surgery duration, anesthesia duration, and American Society of Anesthesiologists (ASA) class) between the three groups. Heart rate was significantly different in all study time points between the three groups (P < 0.001), but mean arterial pressure and systolic and diastolic blood pressure showed no significant difference (P > 0.05) throughout the study. Assessment of hyperalgesia using the tactile test revealed a higher incidence of hyperalgesia in the remifentanil group in 0.5, 2, 6,12, and 24 hours after surgery compared to the other two groups, which was statistically significant between the groups at 0.5, 2, and 6 hours after surgery (P < 0.05). Shivering incidence, Morphine dose in 24 hours post-surgery, morphine dose in the recovery room, and VAS for pain were significantly different during the study between the three groups (P < 0.05). Conclusions: This study demonstrated the efficacy of intraoperative low-dose naloxone (0.25 mu g/kg/h) added to remifentanil infusion on reducing the frequency and severity of acute postoperative hyperalgesia in patients undergoing general anesthesia for laparotomy hysterectomy.