Abstract
It is essential to monitor the end-tidal carbon dioxide (ETCO(2)) during general anesthesia and adjust the tidal volume and respiratory rate (RR). For the purpose of this study, we used a population pharmacodynamic modeling approach to establish the relationship between RR versus ETCO(2) data during general anesthesia in children, and to identify the clinical variables affecting this relationship. A prospective observational study was designed to include 51 patients (aged ≤ 12 years), including users of antiepileptic drugs (levetiracetam, valproic, or phenobarbital (n = 21)) and non-users (n = 30), scheduled to receive general anesthesia during elective surgery. When the ETCO(2) was at 40 mmHg, the RR was adjusted 1 breath per every 2 min until the ETCO(2) was 30 mmHg and recovered to 40 mmHg. Pharmacodynamic analysis using a sigmoid E(max) model was performed to assess the RR-ETCO(2) relationship. As RR varied from 3 to 37 breaths per minute, the ETCO(2) changed from 40 to 30 mmHg. Hysteresis between the RR and ETCO(2) was observed and accounted for when the model was developed. The C(e50) (RR to achieve 50% of maximum decrease in ETCO(2); i.e. 35 mmHg) was 20.5 in non-users of antiepileptic drugs and 14.9 in those on antiepileptic drug medication. The values of γ (the steepness of the concentration-response relation curve) and k(eo) (the first-order rate constant determining the equilibration between the RR and ETCO(2)) were 7.53 and 0.467 min(-1), respectively. The C(e50) and ETCO(2) data fit to a sigmoid E(max) model. In conclusion, the RR required to get the target ETCO(2) was much lower in children patients taking antiepileptic drugs than that of non-user children patients during the general anesthesia.