Pretreatment with nafamostat mesilate, a kallikrein inhibitor, to prevent withdrawal response associated with rocuronium

Background and Goal of Study: Following the anesthetic induction with thiopental or propofol, the injection pain of roucuronium has been reported to occur in 22-84% of adults. Little is known about the mechanisms by which rocuronium triggers injection pain. According to Borgeat et al., however, following an intravenous injection of rocuronium, due to the release of alogenic substances associated with kallikrein-kinin system as bradykinin, the polymodal nociceptor present in the vascular wall is stimulated and this may lead to the occurrence of pain. Nafamostat mesilate is a synthetic kallikrein inhibitor, and it can be used in patients with acute pancreatitis or disseminated intravascular coagulation. This randomized, double-blind, placebo-controlled study was conducted to examine the preventive effect of nafamostat mesilate, a kallikein inhibitor, on withdrawal response associated with injection of rocuronium. Materials and Methods: Ninety ASA physical status I or II patients, aged 18-65 years, were randomly received either a 1.5 ml solution containing 1.5 mg nafamosatat mesilate diluted in 5% glucose solution or 1.5 ml 5% glucose solution. Induction of anesthesia was performed using thiopental 5 mg/kg. After confirming loss of consciousness, a tourniquet was applied to the mid forearm sufficient to block venous flow. The test solution was then administered. One minute after the administration of the test solution, the tourniquet was removed and 0.6 mg/kg rocuronium was administrated immediately. The patient's response to the injection of rcuronim was graded on a four-point scale in a double-blind manner.Prior to the administration of nafamostat and 5 and 10 minutes following it, activated coagulation time and plasma potassium concentration were measured. Results: The incidence of withdrawal was 68.9% in control group and 24.4% in nafamostat group (P < 0.001). The number of patients who showed generalized movement (response 4) with rocuronium injection was significantly lower: 1 (2.2%) for the nafamostat group patients and 15 (33.3%) for the control group (P < 0.001). At 5 and 10 minutes following the administration of nafamostat, the measured concentrations of potassium and ACT showed no significant differences compared to baseline value. Conclusion: The pre-treatment with nafamostat mesilate 1.5 mg significantly prevented withdrawal response associated with injection of rocuronium.