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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2018

Open Access 01-12-2018 | Research article

Nutritional ketosis delays the onset of isoflurane induced anesthesia

Authors: Csilla Ari, Zsolt Kovács, Cem Murdun, Andrew P. Koutnik, Craig R. Goldhagen, Christopher Rogers, David Diamond, Dominic P. D’Agostino

Published in: BMC Anesthesiology | Issue 1/2018

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Abstract

Background

Ketogenic diet (KD) and exogenous ketone supplements can evoke sustained ketosis, which may modulate sleep and sleep-like effects. However, no studies have been published examining the effect of ketosis on the onset of general isoflurane induced anesthesia. Therefore, we investigated the effect of the KD and different exogenous ketogenic supplements on the onset of akinesia induced by inhalation of isoflurane.

Methods

We used a high fat, medium protein and low carbohydrate diet (KD) chronically (10 weeks) in the glucose transporter 1 (GLUT1) deficiency (G1D) syndrome mice model and sub-chronically (7 days) in Sprague-Dawley (SPD) rats. To investigate the effect of exogenous ketone supplements on anesthetic induction we also provided either 1) a standard rodent chow diet (SD) mixed with 20% ketone salt supplement (KS), or 2) SD mixed with 20% ketone ester supplement (KE; 1,3 butanediol-acetoacetate diester) to G1D mice for 10 weeks. Additionally, SPD rats and Wistar Albino Glaxo Rijswijk (WAG/Rij) rats were fed the SD, which was supplemented by oral gavage of KS or KE for 7 days (SPD rats: 5 g/kg body weight/day; WAG/Rij rats: 2.5 g/kg body weight/day). After these treatments (10 weeks for the mice, and 7 days for the rats) isoflurane (3%) was administered in an anesthesia chamber, and the time until anesthetic induction (time to immobility) was measured. Blood ketone levels were measured after anesthetic induction and correlation was calculated for blood beta-hydroxybutyrate (βHB) and anesthesia latency.

Results

Both KD and exogenous ketone supplementation increased blood ketone levels and delayed the onset of isoflurane-induced immobility in all investigated rodent models, showing positive correlation between the two measurements. These results demonstrate that elevated blood ketone levels by either KD or exogenous ketones delayed the onset of isoflurane-induced anesthesia in these animal models.

Conclusions

These findings suggest that ketone levels might affect surgical anesthetic needs, or could potentially decrease or delay effects of other narcotic gases.
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Metadata
Title
Nutritional ketosis delays the onset of isoflurane induced anesthesia
Authors
Csilla Ari
Zsolt Kovács
Cem Murdun
Andrew P. Koutnik
Craig R. Goldhagen
Christopher Rogers
David Diamond
Dominic P. D’Agostino
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2018
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-018-0554-0

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