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

Background. Subanaesthetic concentrations of volatile anaestheticssignificantly affect the respiratory response to hypoxia andhypercapnoeia. Individuals with an inherited blunted respiratorydrive are more affected than normal individuals. To test thehypothesis that subjects with blunted hypercapnoeic respiratorydrive are diversely affected by different anaesthetics, we studiedthe effects of three volatile anaesthetics on the control ofbreathing in C3H/HeJ (C3) mice, characterized by a blunted hypercapnoeicrespiratory response. Methods. Using whole body plethysmography, we assessed respiratoryrate (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 exposedto 8% carbon dioxide. Data were analysed by two-way-analysisof variance with post hoc tests and Bonferroni correction. Results. RR was unaffected during sevoflurane anaesthesia upto 1.0 MAC. Likewise, sevoflurane at 1.5 MAC affected RR lessthan either isoflurane (P=0.0014) or desflurane (P=0.0048).The increased RR to a carbon dioxide challenge was blocked byall three anaesthetics even at the lowest concentration, andremained depressed during recovery (P<0.0001). Tidal volumewas unaffected by all three anaesthetics. Conclusions. In C3 mice, spontaneous ventilation was less affectedduring sevoflurane compared with either isoflurane or desfluraneanaesthesia. However, the RR response to hypercapnoeia was abolishedat 0.5 MAC for all the anaesthetic agents and remained depressedeven at the end of recovery. Our data suggest that differentvolatile anaesthetics have varying effects on the control ofbreathing frequency but all block the respiratory response tocarbon dioxide. Therefore, a genetic predisposition to a bluntedcarbon dioxide response represents a susceptibility factor thatinteracts with hypercapnoeic hypoventilation during maintenanceof anaesthesia and in the emergence from anaesthesia, regardlessof the agent used. Br J Anaesth 2004; 92: 697–703