Effects of different administration routes of lipid emulsion on bupivacaine-induced cardiotoxicity in rats

Abstract

Objective To evaluate the effects of different administration routes of lipid emulsion on bupivacaine-induced cardiotoxicity in rats. Methods Forty-eight clean healthy adult male Sprague-Dawley rats, weighing 300-350 g, were divided into 6 groups (n=8 each) using a random number table: IV infusion of normal saline (NS) group (group VN), IV infusion of lipid emulsion group (group VL), duodenal infusion of NS group (group DN), duodenal infusion of lipid emulsion group (group DL), intraperitoneal infusion of NS group (group PN) and intraperitoneal infusion of lipid emulsion group (group PL). In VN and VL groups, preheated NS and 20% lipid emulsion 3 ml·kg-1·min-1 were infused via the femoral vein for 5 min, respectively, and then 0.75% bupivacaine was infused at the rate of 2 mg·kg-1·min-1 until cardiac arrest happened.Preheated NS and 20% lipid emulsion 15 ml/kg were infused via the duodenum (over 1 min, at a constant rate) in DN and DL groups, respectively, and were intraperitoneally infused in PN and PL groups, respectively, followed by an infusion of 0.2 ml/min for 15 min in DN, DL, PN and PL groups.Then 0.75% bupivacaine was infused via the left femoral vein at a rate of 2 mg·kg-1·min-1 until cardiac arrest happened.The time to ventricular arrhythmia, mean arterial pressure (MAP) decreasing to 50% of the baseline and cardiac arrest was recorded.The amount of bupivacaine consumed was calculated immediately after ventricular arrhythmia occurred (T0), immediately after MAP decreased to 50% of the baseline (T1) and immediately after occurrence of cardiac arrest (T2). Arterial blood samples were collected at T0-2 for determination of the concentration of bupivacaine in plasma by high-performance liquid chromatography. Results Compared with group VN, the time to ventricular arrhythmia, MAP decreasing to 50% of the baseline and cardiac arrest was significantly prolonged, and the amount of bupivacaine consumed was increased at T0-2 in group VL (P 0.05). Compared with group VL, the time to ventricular arrhythmia, MAP decreasing to 50% of the baseline and cardiac arrest was significantly shortened, and the amount of bupivacaine consumed was decreased at T0-2 in DL and PL groups (P 0.05). Conclusion IV infusion of lipid emulsion can decrease bupivacaine-induced cardiotoxicity when compared with duodenal and intraperitoneal infusion in rats. Key words: Lipid emulsions, intravenous; Bupivacaine; Drug toxicity