Lipid emulsion facilitates reversal from volatile anesthetics in a rodent model

Abstract

Background

Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly lipophilic drugs. Considering the lipophilic property of volatile anesthetics, we hypothesized that lipid emulsion could reverse general anesthesia.

Methods

Using adult rats, we tested the effect of lipid emulsion infusion on time to emergence after discontinuation of sevoflurane and isoflurane, and further evaluated restoration of righting reflex under continuous sevoflurane anesthesia. Electroencephalogram during lipid emulsion infusion was also investigated under continuous sevoflurane inhalation. The effect of lipid emulsion on sevoflurane-induced respiratory and hemodynamic depressions was evaluated by measuring respiratory rate, PaCO₂ (arterial partial pressure of CO₂), blood pressure, and heart rate. The binding property of lipid emulsion on sevoflurane and isoflurane was assessed using in vitro setting with a conical flask.

Results

Lipid emulsion infusion significantly decreased time to emergence from sevoflurane anesthesia (131 ± 53 vs. 237 ± 69 s) and restored righting reflex during continuous sevoflurane inhalation, by comparing normal saline infusion. Consistent with the behavioral findings, the electroencephalogram under continuous sevoflurane showed decreased power of the δ bands at 5 min after the initiation of lipid emulsion infusion. In addition to reversing hypnosis, lipid emulsion recovered respiratory as well as hemodynamic depressions induced by sevoflurane. Decreased time to emergence was observed also in isoflurane anesthesia (203 ± 111 vs. 314 ± 154 s). To investigate the binding mechanism of lipid emulsion infusion, in vitro experiments revealed significantly decreased anesthetic concentrations of sevoflurane and isoflurane by mixing with lipid emulsion.

Conclusions

Lipid emulsion facilitated reversal from volatile anesthetics, as shown by several parameters. As lipid emulsion could bind to volatile anesthetics and simply decrease their effects, our findings suggest that lipid emulsion is a potentially useful agent to reverse general anesthesia.

Keywords:

• Lipid emulsion
• anesthesia
• sevoflurane
• isoflurane
• rats

Acknowledgments

We would like to thank Junko Kawawaki, MS (Central Laboratory, Osaka City University Graduate School of Medicine, Osaka, Japan) for technical assistance and Honyaku Center Inc. (Osaka, Japan) for English language editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science [16K10947, 18K16490], Tokyo, Japan.