It is essential to monitor the end-tidal carbon dioxide (ETCO2) 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 ETCO2 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 ETCO2 was at 40 mmHg, the RR was adjusted 1 breath per every 2 min until the ETCO2 was 30 mmHg and recovered to 40 mmHg. Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the RR-ETCO2 relationship. As RR varied from 3 to 37 breaths per minute, the ETCO2 changed from 40 to 30 mmHg. Hysteresis between the RR and ETCO2 was observed and accounted for when the model was developed. The Ce50 (RR to achieve 50% of maximum decrease in ETCO2; 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 keo (the first-order rate constant determining the equilibration between the RR and ETCO2) were 7.53 and 0.467 min-1, respectively. The Ce50 and ETCO2 data fit to a sigmoid Emax model. In conclusion, the RR required to get the target ETCO2 was much lower in children patients taking antiepileptic drugs than that of non-user children patients during the general anesthesia.

中文翻译：

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儿童麻醉期间呼吸频率和呼气末二氧化碳值的药效学模型。

在全身麻醉期间监测呼气末二氧化碳 (ETCO2) 并调整潮气量和呼吸频率 (RR) 至关重要。出于本研究的目的，我们使用群体药效学建模方法来建立儿童全身麻醉期间 RR 与 ETCO2 数据之间的关系，并确定影响这种关系的临床变量。一项前瞻性观察性研究旨在纳入 51 名患者（年龄 ≤ 12 岁），其中包括服用抗癫痫药物（左乙拉西坦、丙戊酸或苯巴比妥（n = 21））和计划接受全身麻醉的非使用者（n = 30）在择期手术中。当ETCO2为40 mmHg时，每2分钟调整1次呼吸，直到ETCO2为30 mmHg并恢复到40 mmHg。使用 sigmoid Emax 模型进行药效分析以评估 RR-ETCO2 关系。当 RR 从每分钟 3 到 37 次呼吸变化时，ETCO2 从 40 变为 30 mmHg。RR 和 ETCO2 之间的滞后被观察到并在模型开发时被考虑在内。Ce50（达到 ETCO2 最大下降 50% 的 RR；即 35 mmHg）在非抗癫痫药物使用者中为 20.5，在服用抗癫痫药物者中为 14.9。γ（浓度-响应关系曲线的陡度）和 keo（决定 RR 和 ETCO2 之间平衡的一级速率常数）的值分别为 7.53 和 0.467 min-1。Ce50 和 ETCO2 数据符合 sigmoid Emax 模型。综上所述，