J Anesth Perioper Med. 2017;4(5):199-204. https://doi.org/10.24015/ebcmed.japm.2017.0014

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

Can-Sheng Gong1,3*, Xiao-Jia Wang1,4*, Jin Liu1,3, Da-Qing Liao1, Ru-Rong Wang1,3, Han Huang1,2, and Cheng Zhou1,3

From 1Lab of Anesthesia & Critical Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China; 2Department of Anesthesiology, West China Second University Hospital of Sichuan University, Chengdu, China; 3Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China; 4Department of Anesthesiology, Sichuan Provincial People's Hospital, Chengdu, China.

*The first two authors contributed equally to this study.

Correspondence to Han Huang at huanghan1981@hotmail.com or Cheng Zhou at zhouc@163.com.

EBCMED ID: ebcmed.japm.2017.0014 DOI: 10.24015/ebcmed.japm.2017.0014


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.

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.

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.

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.

Article Type
Original Article

Declaration of Interests
The authors have no conflicts of interest for this work to declare.

This work was supported by National Scientific Foundation of China (81401623 to H. H. and 81571353 to J.L. and 81401139 to C.Z.) and by the grant from Science & Technology Department of Sichuan Province, China (2016HH0066 to H.H.).

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