Influence of bupivacaine injection dose rate on cardiovascular depression, subsequent hemodynamic course, and related bupivacaine plasma levels in piglets

Abstract

Systemic local anesthetic (LA) toxicity resulting from inadvertent intravascular injection of LA is a rare but potentially fatal event. Early recognition of intravascular injection and approaches to improve therapeutic safety are required. This study investigated the influence of intravascular injection dose rate of bupivacaine on bupivacaine plasma levels and timing of LA-induced cardiovascular compromise. Forty-five piglets, anesthetized with sevoflurane, were randomized into three groups. Bupivacaine was intravenously infused at a rate of 1, 4, or 16mg/kg/min (groups A, B, and C, respectively) until mean arterial pressure (MAP) dropped to 50% of initial value. Thereafter, bupivacaine infusion was stopped and spontaneous hemodynamic course was observed. Time to MAP50%, amount of bupivacaine infused, bupivacaine plasma level at infusion stop, spontaneous survivors, or time from bupivacaine stop to circulatory arrest were recorded. Median time to MAP50% was 297, 119, and 65s, respectively, in groups A, B, and C (P<0.001). Median corresponding total amounts of bupivacaine infused were 5.0, 7.8, and 17.0mg/kg (P<0.01), and median bupivacaine plasma levels were 53.8, 180.0, and 439.8μmol/l (P<0.001). Five of 15 piglets in group A recovered spontaneously; in groups B and C, all animals died within 120 and 21s, respectively. Higher dose rates of bupivacaine showed much higher plasma bupivacaine levels related to absolute infused dose at MAP50% and were associated with an increased mortality. Slow administration of LA is recommended to allow timely detection and stopping of inadvertent intravascular administration.