Effects of Remifentanil Pretreatment on Bupivacaine Cardiotoxicity in Rats

Abstract

Unintentional intravascular administration of bupivacaine may cause local anesthetic systemic toxicity (LAST). Although many systems are affected in LAST, the cardiovascular effects can be life-threatening. Remifentanil is a selective, ultra-short-acting, µ-opioid receptor agonist opioid. This study assessed the effects of combined pretreatment with intravenous lipid emulsion (ILE) and remifentanil on the cardiotoxicity caused by bupivacaine in an experimental model of anesthetized rats. The rats were divided into three groups. Group B received a saline pretreatment plus a bupivacaine, group L received ILE pretreatment plus a bupivacaine, and in group R, remifentanil was infused intravenously, plus ILE pretreatment plus a bupivacaine. The electrocardiogram tracing, invasive arterial pressure, and heart rate (HR) of rats were monitored continuously. Arterial blood gas analysis was performed in all groups. Arterial blood gas analysis revealed that the baseline pH (7.38 ± 0.31, 7.39 ± 0.41, and 7.37 ± 0.02 for groups B, L, and R, respectively), PaO₂ (198.5 ± 9.45, 196.1 ± 32.3, and 197.7 ± 9.25 mmHg, respectively), and PaCO₂ (37.8 ± 4.91, 37.4 ± 4.85, and 36.9 ± 4.42 mmHg, respectively) were similar in the groups (p > 0.05). Time to first alteration in QRS complex, time to first arrhythmia, time to 25, 50, and 75% reductions in HR, time to 25, 50, and 75% reductions in MAP, and time to asystole were recorded. Widening of the QRS complex was found 41.8 ± 16.6, 88.5 ± 7.91, and 103.0 ± 15.7 s after initiating the bupivacaine infusion in groups B, L, and R, respectively. Time elapsed until 25% reduction in HR was found 136.5 ± 50.7, 284.7 ± 31.7, and 292.0 ± 46.0 s for groups B, L, and R, respectively, and that until 25% reduction in MAP was found 101.7 ± 14.3, 245.0 ± 36.6, and 237.6 ± 52.6 s, respectively. Arrhythmia was observed after 135.2 ± 27.4, 172.4 ± 18.1, and 176.2 ± 23.0 s in groups B, L, and R, respectively. Finally, asystole occurred after 553.6 ± 74.4, 766.7 ± 64.8, and 800.1 ± 94.7 s in groups B, L, and R, respectively. This finding indicates that the survival time of rats administered pretreatment with ILE plus remifentanil and those given ILE was observed to be longer. Additionally, this study found that intravenous lipid emulsion plus remifentanil pretreatment did not result in better durations in terms of formation of bupivacaine intoxication and asystole compared to lipid pretreatment alone.

Keywords: Cardiotoxicity; Intravenous lipid emulsion; LAST; Local anesthetic systemic toxicity; Rats; Remifentanil.