Bupivacaine-induced cardiotoxicity and lipid emulsion

We read the recently published article, “Effects of Insulin + Glucose Pretreatment on Bupivacaine Cardiotoxicity in Rats,” in Human and Experimental Toxicology. ¹ Lipid emulsion has been widely used to treat local anesthetic toxicity. ^2,3 The following comments should be considered in the interpretation of this laboratory study. First, the normal saline group received 2 mL/kg for 10 min before the administration of 0.5% bupivacaine (3 mg/kg/min), whereas the lipid emulsion group received 10 mg/kg of 20% ClinOleic for 10 min, which corresponds to 0.05 mL/kg of 20% ClinOleic, prior to the administration of bupivacaine (3 mg/kg/min). ¹ In terms of pretreatment drug volume before administration of bupivacaine, the total volume (0.015–0.0225 mL) of lipid emulsion was 40 times less than that (0.6–0.9 mL) of normal saline. Otherwise, Pişkin and Aydın may have likely miswritten 10 mg/kg 20% ClinOleic instead of 10 mL/kg 20% ClinOleic. ¹ The lipid emulsion dosage regimen recommend by the American Society of Regional Anesthesia and Pain Medicine for treatment of local anesthetic toxicity in a patient with body weight less than 70 kg is as follows: intravenous bolus administration (1.5 mL/kg) and continuous infusion (0.25 mL/kg/min) of 20% lipid emulsion. ⁴ In addition, another study used lipid emulsion pretreatment at 3 mL/kg/min for 5 min before intravenous administration of a toxic dose of bupivacaine in rats. ⁵ Moreover, resuscitation provided by lipid emulsion was reported to be due to lipid sink, inotropic effect, and associated volume effect. ⁶ Thus, it would be more reasonable to use the same volume of pretreatment drug (normal saline: 2 mL/kg vs. 20% ClinOleic: 0.05 or 10 mL/kg) because resuscitation of lipid emulsion is partially ascribed to the volume effect induced by lipid emulsion itself and to consider the dosage of lipid emulsion recommended by the American Society of Regional Anesthesia and Pain Medicine and used by a previous study. ^{4 –6} Second, analysis of variance (ANOVA) followed by Tukey’s test or the Kruskal–Wallis test followed by Dunn’s test was used to analyze the data in figures 1 and 2. ¹ However, to reduce type 1 errors, depending on the normality of data in figures 1 and 2, it would be more reasonable to use two-way repeated measures ANOVA, followed by Bonferroni’s multiple comparison test, or linear mixed model, to analyze data in figures 1 and 2 that show a parametric and nonparametric distribution. ^1,7