Population pharmacokinetic and safety analysis of ropivacaine used for erector spinae plane blocks.

INTRODUCTION: Erector spinae plane blocks have become popular for thoracic surgery. Despite a theoretically favorable safety profile, intercostal spread occurs and systemic toxicity is possible. Pharmacokinetic data are needed to guide safe dosing. METHODS: Fifteen patients undergoing thoracic surgery received continuous erector spinae plane blocks with ropivacaine 150 mg followed by subsequent boluses of 40 mg every 6 hours and infusion of 2 mg/hour. Arterial blood samples were obtained over 12 hours and analyzed using non-linear mixed effects modeling, which allowed for conducting simulations of clinically relevant dosing scenarios. The primary outcome was the Cmax of ropivacaine in erector spinae plane blocks. RESULTS: The mean age was 66 years, mean weight was 77.5 kg, and mean ideal body weight was 60 kg. The mean Cmax was 2.5 ±1.1 mg/L, which occurred at a median time of 10 (7-47) min after initial injection. Five patients developed potentially toxic ropivacaine levels but did not experience neurological symptoms. Another patient reported transient neurological toxicity symptoms. Our data suggested that using a maximum ropivacaine dose of 2.5 mg/kg based on ideal body weight would have prevented all toxicity events. Simulation predicted that reducing the initial dose to 75 mg with the same subsequent intermittent bolus dosing would decrease the risk of toxic levels to <1%. CONCLUSION: Local anesthetic systemic toxicity can occur with erector spinae plane blocks and administration of large, fixed doses of ropivacaine should be avoided, especially in patients with low ideal body weights. Weight-based ropivacaine dosing could reduce toxicity risk. TRIAL REGISTRATION NUMBER: NCT04807504; clinicaltrials.gov.