A randomized clinical trial of the effects of ultra‐low‐dose naloxone infusion on postoperative opioid requirements and recovery

Background Tolerance to remifentanil during sevoflurane anesthesia may increase postoperative analgesic requirements. Low-dose naloxone not only has been shown to block the development of acute opioid tolerance but also to ameliorate undesired opioid-induced side effects. We hypothesized that naloxone prevents the acute opioid tolerance produced by a large dose of remifentanil, and reduces the incidence of opioid-induced side effects. Methods Seventy-two patients undergoing open colorectal surgery were randomly assigned to receive intraoperative remifentanil (1) small dose at 0.1 μg/kg/min; (2) large dose at 0.30 μg/kg/min; or (3) large dose at 0.30 μg/kg/min combined with low-dose naloxone at 0.25 μg/kg/h just after the induction. Cumulative morphine consumption, postoperative pain scores, incidence of opioid-related side effects, time to recovery of bowel function, and length of hospital stay were recorded. Results Cumulative morphine consumption at 24 h after surgery was higher in the large-dose remifentanil group (28 ± 12 mg) compared with the small-dose remifentanil group (17 ± 12 mg), and large-dose remifentanil–naloxone group (18 ± 9 mg), (P < 0.001). The median time to return of bowel function was shorter in the large-dose remifentanil–naloxone group than the other two groups (P < 0.05). The median length of hospital stay was lower in the large-dose remifentanil–naloxone group (8 [interquartile range: 8–12] days) compared with the small-dose remifentanil group (12 [interquartile range: 9–15] days) and large-dose remifentanil group (12 [interquartile range: 10–13] days), (P < 0.001). Conclusion Naloxone infusion prevented the acute opioid tolerance, provided a quicker recovery of bowel function, and reduced the length of hospital stay after open colorectal surgery.