Equipotent Subanesthetic Concentrations of Sevoflurane and Xenon Preventing Cold-stimulated Vocalization of Neonatal Rats

Abstract

Abstract Background: The effects of inhaled anesthetics on the developing brain are studied using neonatal rodents exposed to fractions of minimum alveolar concentration (to avoid cardiorespiratory compromise). However, these fractions cannot be assumed to be equipotent. Xenon’s anesthetic and neuroprotective properties warrant investigation in these models. Therefore, equipotent, subanesthetic concentrations of inhaled anesthetics are needed. Methods: Forty-eight Wistar rats (Charles River Laboratories, Kent, United Kingdom) on postnatal day 9 were randomized to eight concentrations of inhaled anesthetics: isoflurane, sevoflurane, or xenon. Exposure was closely monitored in individual metal-based chambers resting on a 35°C mat to maintain normothermia. A 25°C mat was used to stimulate vocalization and a sound recording made (1 min, 1 to 100 kHz). Rectal temperature or partial pressure of carbon dioxide and pH of mixed arteriovenous blood were measured immediately after the exposure. Concentration–response models were constructed using logistic regression (dependent variable: vocalization and explanatory variable: concentration). The effects of all other explanatory variables were assessed by inserting them individually into the model. Results: The effective inhaled concentrations preventing cold-stimulated vocalization in 50 and 95% of neonatal rats (EiC50 and EiC95) on postnatal day 9 were 0.46 and 0.89% sevoflurane and 20.15 and 34.81% xenon, respectively. The effect on the EiC50 of all other explanatory variables, including duration, was minimal. Stability of EiC50 isoflurane was not achieved over three durations (40, 80, and 120 min exposure). Partial pressure of carbon dioxide and pH in mixed arteriovenous blood appeared normal. Conclusions: The authors report equipotent subanesthetic concentrations of sevoflurane and xenon in neonatal rats with preserved cardiopulmonary function. This may be useful in designing neonatal rodent models of anesthesia.