Combination of nefopam and remifentanil is more effective to reduce rocuronium-induced withdrawal response compared with remifentanil alone: a prospective, double-blinded, randomized control study

Background: We investigated the effect of combination of nefopam and remifentanil under the hypothesis that nefopam would effectively prevent rocuronium-induced withdrawal response by blocking serotonin receptors and providing a synergistic or additional effect with remifentanil. Methods: After receiving Institutional Review Board approval, 76 patients aged between 20 and 65 years with American Society of Anesthesiologists physical statuses of I or II were randomly allocated to the control group and nefopam group. In the control group, 102 ml of 0.9% sodium chloride solution was infused one hour before surgery at 100 ml/h. In the nefopam group, 20 mg nefopam (2 ml) in 100 ml of a 0.9% sodium chloride solution was infused one hour before surgery at 100 ml/h. Rocuronium (0.6 mg/kg) was injected after the induction of anesthesia with remifentanil and propofol at target concentrations of 2.0 ng/ml and 3.0 μg/ml, respectively. The grades of rocuronium-induced withdrawal response were evaluated using a four-point scale. The hemodynamics and respiratory rates were recorded upon operating room arrival, after anesthesia induction, and one minute post-injection of rocuronium. Results: Two patients (nefopam group) were excluded due to incomplete infusion and side effects; thus, 74 patients were finally analyzed. The overall incidence of rocuronium-induced withdrawal response was significantly lower in nefopam group (27.8%, n = 36) than in control group (60.5%, n = 38) (P = 0.005). Conclusions: The combination of nefopam (20 mg) and remifentanil is more effective at reducing rocuronium-induced withdrawal response than remifentanil infusion alone with stable hemodynamics. Keywords: Injection site reaction; Nefopam; Remifentanil; Rocuronium