Prediction of expiratory desflurane and sevoflurane concentrations in lung-healthy patients utilizing cardiac output and alveolar ventilation matched pharmacokinetic models: A comparative observational study

Abstract

The Gas Man simulation software provides an opportunity to teach, understand and examine the pharmacokinetics of volatile anesthetics. The primary aim of this study was to investigate the accuracy of a cardiac output and alveolar ventilation matched Gas Man model and to compare its predictive performance with the standard pharmacokinetic model using patient data.Therefore, patient data from volatile anesthesia were successively compared to simulated administration of desflurane and sevoflurane for the standard and a parameter-matched simulation model with modified alveolar ventilation and cardiac output. We calculated the root-mean-square deviation (RMSD) between measured and calculated induction, maintenance and elimination and the expiratory decrement times during emergence and recovery for the standard and the parameter-matched model.During induction, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [induction (desflurane), standard: 1.8 (0.4) % Atm, parameter-matched: 0.9 (0.5) % Atm., P = .001; induction (sevoflurane), standard: 1.2 (0.9) % Atm, parameter-matched: 0.4 (0.4) % Atm, P = .029]. During elimination, RMSDs for the standard Gas Man simulation model were higher than for the parameter-matched Gas Man simulation model [elimination (desflurane), standard: 0.7 (0.6) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .001; elimination (sevoflurane), standard: 0.7 (0.5) % Atm, parameter-matched: 0.2 (0.2) % Atm, P = .008]. The RMSDs during the maintenance of anesthesia and the expiratory decrement times during emergence and recovery showed no significant differences between the patient and simulated data for both simulation models.Gas Man simulation software predicts expiratory concentrations of desflurane and sevoflurane in humans with good accuracy, especially when compared to models for intravenous anesthetics. Enhancing the standard model by ventilation and hemodynamic input variables increases the predictive performance of the simulation model. In most patients and clinical scenarios, the predictive performance of the standard Gas Man simulation model will be high enough to estimate pharmacokinetics of desflurane and sevoflurane with appropriate accuracy.

Conflict of interest statement

Stefan Schumann has a consulting contract with Gründler GmbH Freudenstadt, Germany (no relationship to this study). James H. Philip received a speaking honorarium and travel expenses from AbbVie in 2016. None of the other authors has any conflict of interest.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1

Gas Man Picture (top) and Graph (bottom) after 2 hours and 47 minutes of sevoflurane administration of 1.0 MAC expiratory. DEL, delivered sevoflurane concentration (% of 1 Atm); CKT, circuit; ALV, alveolar; ART, arterial blood; VRG, vessel-rich-group; MUS, muscular; FAT, fat; VEN, venous blood; FGF, fresh gas flow; VA, alveolar ventilation; CO, cardiac output. After 2 hours and 47 minutes, the administration of sevoflurane was stopped, the circuit was opened (non rebreathing) and the FGF was increased to 10 L/min. The Gas Man Graph (bottom) indicates the FGF, the DEL and the course of anesthetic tension in the chosen compartments over time. The predictive performance of this simulation (performed with the standard Gas Man simulation model) was compared to the parameter-matched Gas Man model (including individually adapted hemodynamic and respiratory variables). The minimum alveolar concentration (MAC) in this exemplary simulation used in this study was 2.1% of 1 Atm, indicated by the dotted line in the bottom part of the figure. In every simulation that was performed for this study, we used the same age-adjusted MAC as displayed by the anesthesia machine (Dräger Perseus A500, Dräger Medical).[10]

Figure 2

Mean expiratory concentrations of desflurane and sevoflurane during induction and elimination, normalized to 1.0 age-related MAC.[10] FE_DES_P = mean expiratory fraction of desflurane for patients, FE_DES_S = mean expiratory fraction of desflurane for the standard Gas Man model, FE_DES_E = mean expiratory fraction of desflurane for the parameter-matched Gas Man model. FE_SEV_P = mean expiratory fraction of desflurane for patients, FE_SEV_S = mean expiratory fraction of desflurane for the standard Gas Man model, FE_SEV_E = mean expiratory fraction of desflurane for the parameter-matched Gas Man model.

Figure 3

Comparison of decrement times (dec.time) for desflurane and sevoflurane between the measured patient data (‘Patient’) and simulation data from the standard (‘Standard’) and the parameter-matched (‘Enhanced’) Gas Man simulation model. All decrement times are displayed in the percentage of expiratory concentration of 1.0 MAC. There was no statistically significant difference between the decrement times of the patient and the simulation data Mann-Whitney U test). On each box, the central mark indicates the second quartile, the bottom, and top edges indicate quartiles (25th percentile and 75th percentile). On each box, the whiskers indicate the range of data points. Outliers are plotted individually (‘+’).