The mechanism by which volatile anesthetics cause immobility to noxious stimulation remains a mystery. Can changes in energy levels affect the sensitivity to anesthetics? Dr. Zhongcong Xie, Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, and colleagues sought to determine whether 2-deoxy-d-glucose (2-DG), an analog of glucose, and/or 3-nitropropionic acid, a compound which can deplete ATP levels, can enhance isoflurane anesthesia, and whether idebenone and L-carnitine, which can rescue deficits of energy, can reverse these effects. The results of their analysis are described in the article titled “2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice,” which was published in the current issue of Anesthesia & Analgesia.
The percentage of mice that lost their righting reflex at a given concentration of isoflurane was greater when they were pretreated with 2-DG as well as 3-NP. Idebenone, an analogue of coenzyme Q10 that has been reported to rescue ATP levels in mitochondrial dysfunction, inhibited the enhancing effects of 2-DG. Similarly, 2-DG did not decrease ATP levels in cultured cells pretreated with idebenone. Thus, 2-DG might enhance isoflurane-induced anesthetic effects by reducing energy (e.g., ATP) levels, pending further investigation. In addition, exposing H4 human neuroglioma cells to 2% isoflurane for 60, 90, and 180 minutes reduced ATP levels, but not for 30 minutes. Similar findings were seen when measuring ATP levels in mice brain tissue.
The idea that general anesthesia is linked to metabolic rate or ATP levels is not new. These results are preliminary. As the authors admit, the effects on anesthesia depth could be due to a pharmacokinetic mechanism rather than a pharmacodynamic mechanism. Although anesthetics have been well documented to change mitochondrial function, whether energy levels in the mitochondria affect the dose requirements of inhaled anesthetics to cause immobility or unconsciousness remains to be seen.