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Intramuscular injection of sevoflurane detects malignant hyperthermia predisposition in susceptible pigs
Frank Schuster1, Thomas Metterlein, Sabrina Negele
1Department of Anesthesiology, University of Würzburg, Germany. schuster_f@klinik.uni-wuerzburg.de
Background:
The authors hypothesized that intramuscular sevoflurane injection allows diagnostic differentiation between malignant hyperthermia-susceptible (MHS) and -nonsusceptible (MHN) pigs by measurement of intramuscular lactate and carbon dioxide partial pressure (PCO2), and that dantrolene reduces the sevoflurane-induced PCO2 increase.
Methods:
With approval of the local animal care committee, microdialysis probes with attached microtubing for sevoflurane injection were placed in the adductor muscles of nine MHS and six MHN pigs, and PCO2 probes with microtubing were positioned in the triceps muscle of eight MHS and six MHN pigs. After equilibration, sevoflurane boluses at different concentrations and a sevoflurane-dantrolene bolus were injected synchronously. Lactate, pyruvate, and glucose as well as PCO2 were measured spectrophotometrically, and the rate of PCO2 increase was calculated.
Results:
Intramuscular sevoflurane injection increased local lactate and PCO2 dose dependently, and significantly higher in MHS than in MHN pigs. Measurement of the rate of PCO2 increase allowed a distinct differentiation between single MHS and MHN pigs. No significant increase in PCO2 was found with sevoflurane and dantrolene.
Conclusions:
Local sevoflurane induces a hypermetabolic reaction measured by PCO2 and lactate increases. The reduced PCO2 increase in MHS after sevoflurane and dantrolene injection is likely to be a result of the sevoflurane-mediated calcium release and its antagonism by dantrolene. Sevoflurane may be useful for a less invasive diagnostic test for malignant hyperthermia in humans.
Insights
Intramuscular sevoflurane injection can differentiate malignant hyperthermia-susceptible pigs by measuring carbon dioxide partial pressure (PCO2) and lactate. Dantrolene counteracts sevoflurane
Area of Science:
- Anesthesiology
- Physiology
- Pharmacology
Background:
- Malignant hyperthermia (MH) is a hypermetabolic crisis triggered by volatile anesthetics.
- Current diagnostic methods for MH susceptibility are invasive and complex.
- Intramuscular sevoflurane injection was hypothesized to aid in differentiating MH-susceptible (MHS) from MH-nonsusceptible (MHN) pigs.
Purpose of the Study:
- To evaluate intramuscular sevoflurane injection for diagnosing MH susceptibility in pigs.
- To assess the role of dantrolene in mitigating sevoflurane-induced hypermetabolic responses.
Main Methods:
- Microdialysis probes were used for intramuscular sevoflurane and dantrolene injection in MHS and MHN pigs.
- Carbon dioxide partial pressure (PCO2) and lactate levels were measured in muscle tissue.
- The rate of PCO2 increase was calculated to differentiate between MHS and MHN pigs.
Main Results:
- Intramuscular sevoflurane injection dose-dependently increased local lactate and PCO2.
- These increases were significantly higher in MHS pigs compared to MHN pigs.
- The rate of PCO2 increase effectively differentiated individual MHS and MHN pigs.
Conclusions:
- Local sevoflurane induces a measurable hypermetabolic reaction in pigs.
- Sevoflurane may serve as a less invasive diagnostic tool for malignant hyperthermia.
- Dantrolene antagonized the sevoflurane-induced PCO2 increase, likely via calcium channel modulation.
