Influence of volatile anaesthetics on hypercapnoeic ventilatory responses in mice with blunted respiratory drive

Background. Subanaesthetic concentrations of volatile anaesthetics significantly affect the respiratory response to hypoxia and hypercapnoeia. Individuals with an inherited blunted respiratory drive are more affected than normal individuals. To test the hypothesis that subjects with blunted hypercapnoeic respiratory drive are diversely affected by different anaesthetics, we studied the effects of three volatile anaesthetics on the control of breathing in C3H/HeJ (C3) mice, characterized by a blunted hypercapnoeic respiratory response. Methods. Using whole body plethysmography, we assessed respiratory rate (RR) and pressure amplitude in 11 male C3 mice at rest, during anaesthesia with isoflurane, sevoflurane or desflurane, and during recovery. To test respiratory drive, mice were exposed to 8% carbon dioxide. Data were analysed by two-way-analysis of variance with post hoc tests and Bonferroni correction. Results. RR was unaffected during sevoflurane anaesthesia up to 1.0 MAC. Likewise, sevoflurane at 1.5 MAC affected RR less than either isoflurane (P=0.0014) or desflurane (P=0.0048). The increased RR to a carbon dioxide challenge was blocked by all three anaesthetics even at the lowest concentration, and remained depressed during recovery (P<0.0001). Tidal volume was unaffected by all three anaesthetics. Conclusions. In C3 mice, spontaneous ventilation was less affected during sevoflurane compared with either isoflurane or desflurane anaesthesia. However, the RR response to hypercapnoeia was abolished at 0.5 MAC for all the anaesthetic agents and remained depressed even at the end of recovery. Our data suggest that different volatile anaesthetics have varying effects on the control of breathing frequency but all block the respiratory response to carbon dioxide. Therefore, a genetic predisposition to a blunted carbon dioxide response represents a susceptibility factor that interacts with hypercapnoeic hypoventilation during maintenance of anaesthesia and in the emergence from anaesthesia, regardless of the agent used.