Protective Effect of Emulsified Isoflurane Preconditioning on Cardiac Toxicity Induced by Bupivacaine in Rats

Abstract

Background: Lipid emulsion has been identified as a potent rescuing agent for cardiac arrest caused by local anesthetic overdose. In this animal study, we investigated whether prophylactic infusion of emulsified isoflurane, a mixture of lipid emulsion and isoflurane, could increase the tolerability for bupivacaine-induced cardiac toxicity.Methods: Rats were randomly assigned to receive one of the following treatments: saline, 30% Intralipid, 4% Emulsified Isoflurane (4% EISO), 2% EISO, 0.5% propofol, 0.25% propofol, inhaled isoflurane plus 30% Intralipid, or inhaled isoflurane plus saline, for 15 minutes. Then 0.75% bupivacaine was infused at the rate of 8 ml/kg/min (n=10 in each group). The time needed to induce cardiac arrest was recorded and the bupivacaine dose was calculated. Another set of rats were intubated for mechanical ventilation and catheterized for invasive arterial pressure monitoring while receiving one of the following sedative pretreatments for 15 minutes: 4% EISO, 0.5% propofol, inhaled isoflurane plus saline, or inhaled isoflurane plus 30% Intralipid (n=10 in each group). Then bupivacaine was infused at the rate of 8 ml/kg/min for 120 seconds (sublethal dose). The hemodynamic parameters were recorded till circulation fully recovered.Results: Pretreatment with 4% EISO significantly increased the dose of bupivacaine required to induce cardiac arrest (68.69±7.57 mg/kg vs. 26.61±5.13 mg/kg for saline, P<0.01). Prophylactic infusion of Intralipid alone also increased the bupivacaine tolerability (51.41±9.68 mg/kg, P<0.05 vs. saline), but less efficient than 4% EISO (P<0.05 vs. 4% EISO). Pretreatments with 4% EISO provided best preservation of hemodynamic parameters in the face of circulatory fluctuation caused by sublethal dose of bupivacaine.Conclusions: The 4% emulsified isoflurane preconditioning significantly increases the threshold of bupivacaine-induced cardiac arrest in rats and prevents circulatory instability caused by sublethal dose of bupivacaine. Our results implicate the potential application of emulsified isoflurane as an adjuvant agent in local anesthesia.  Citation:  Can-Sheng Gong, Xiao-Jia Wang, Jin Liu, Da-Qing Liao, Ru-Rong Wang, Han Huang, et al. Protective effect of emulsified isoflurane preconditioning on cardiac toxicity induced by bupivacaine in rats. J Anesth Perioper Med 2017; 4: 199-204. doi:10.24015/JAPM.2017.0014This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.