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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:

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.

SUBMITTER: Weber J

PROVIDER: S-EPMC7886476 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Weber Jonas J Weber Jonas J Mißbach Claudia C Schmidt Johannes J Wenzel Christin C Schumann Stefan S Philip James H JH Wirth Steffen S

Medicine 20210201 6

<h4>Abstract</h4>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 ...[more]

PMID: 33578509

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Project description:BackgroundIntensive care unit (ICU) physicians have extended the minimum alveolar concentration (MAC) to deliver and monitor long-term volatile sedation in critically ill patients. There is limited evidence of MAC's reliability in controlling sedation depth in this setting. We hypothesized that sedation depth, measured by the electroencephalography (EEG)-derived Narcotrend-Index (burst-suppression N_Index 0-awake N_Index 100), might drift downward over time despite constant MAC values.MethodsThis prospective single-centre randomized clinical study was conducted at a University Hospital Surgical Intensive Care Unit and included consecutive, postoperative ICU patients fulfilling the inclusion criteria. Patients were randomly assigned to receive uninterrupted inhalational sedation with isoflurane, sevoflurane, or desflurane. The end-expiratory concentration of the anaesthetics and the EEG-derived index were measured continuously in time-stamped pairs. Sedation depth was also monitored using Richmond-Agitation-Sedation-Scale (RASS). The paired t-test and linear models (bootstrapped or multilevel) have been employed to analyze MAC, N_Index and RASS across the three groups.ResultsThirty patients were recruited (female/male: 10/20, age 64 ± 11, Simplified Acute Physiology Score II 30 ± 10). In the first 24 h, 21.208 pairs of data points (N_Index and MAC) were recorded. The median MAC of 0.58 ± 0.06 remained stable over the sedation time in all three groups. The t-test indicated in the isoflurane and sevoflurane groups a significant drop in RASS and EEG-derived N_Index in the first versus last two sedation hours. We applied a multilevel linear model on the entire longitudinal data, nested per patient, which produced the formula N_Index = 43 - 0.7·h (R2 = 0.76), showing a strong negative correlation between sedation's duration and the N_Index. Bootstrapped linear models applied for each sedation group produced: N_Index of 43-0.9, 45-0.8, and 43-0.4·h for isoflurane, sevoflurane, and desflurane, respectively. The regression coefficient for desflurane was almost half of those for isoflurane and sevoflurane, indicating a less pronounced time-effect in this group.ConclusionsMaintaining constant MAC does not guarantee stable sedation depth. Thus, the patients necessitate frequent clinical assessments or, when unfeasible, continuous EEG monitoring. The differences across different volatile anaesthetics regarding their time-dependent negative drift requires further exploration.Trial registrationNCT03860129.

Project description:As life expectancy increases, more patients ?65 years undergo general anesthesia. Anesthetic agents may contribute to postoperative cognitive dysfunction, and incidence may differ with anesthetic agents or intraoperative anesthesia depth. Responses to anesthetic adjuvants vary among elderly patients. Processed electroencephalography guidance of anesthetic may better ensure equivalent cerebral suppression. This study investigates postoperative cognitive dysfunction differences in elderly patients given desflurane or sevoflurane using processed electroencephalography guidance.IRB approved, randomized trial enrolled consenting patients ?65 years scheduled for elective surgery requiring general anesthesia ?120 minute duration. After written informed consent, patients were randomly assigned to sevoflurane or desflurane. No perioperative benzodiazepines were administered. Cognitive impairment was measured by an investigator blinded to group assignment using mini-Mental Status Examination (MMSE) at baseline; 1, 6, and 24 hours after the end of anesthesia. Mean arterial pressure was maintained within 20% of baseline. Anesthetic dose was adjusted to maintain moderate general anesthesia per processed electroencephalograpy (Patient State Index 25 to 50). The primary outcome measure was intergroup difference in MMSE change 1 hour after anesthesia (median; 95% confidence interval).110 patients consented; 26 were not included for analysis (no general anesthesia; withdrew consent; baseline MMSE abnormality; inability to perform postoperative MMSE; data capture failure); 47 sevoflurane and 37 desflurane were analyzed. There were no significant differences in patient characteristics; intraoperative mean blood pressure (desflurane 86.4; 81.3 to 89.6 versus sevoflurane 82.5; 80.2 to 86.1 mmHg; p?=?0.42) or Patient State Index (desflurane 41.9; 39.0 to 44.0 versus sevoflurane 41.0; 37.5 to 44.0; p?=?0.60) despite a lower MAC fraction in desflurane (0.82; 0.77 to 0.86) versus sevoflurane (0.96; 0.91 to 1.03; p?<?0.001). MMSE decreased 1 hour after anesthesia (p?<?0.001). The decrease at one hour was larger in sevoflurane (-2.5; -3.3 to -1.8) than desflurane (-1.3; -2.2 to -0.5; p?=?0.03). MMSE returned to baseline by 6 hours after anesthesia.For elderly patients in whom depth of anesthesia is maintained in the moderate range, both desflurane and sevoflurane are associated with transient decreases in cognitive function as measured by MMSE after anesthesia, with clinically insignificant differences between them in this setting.ClinicalTrials.gov NCT01199913.

Project description:BackgroundAn increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed.ObjectivesThe aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery.DesignA systematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesA systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019.Eligibility criteriaRCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia.ResultsThirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = -3.32 min (95% CI -4.02 to -2.61)) with a substantial heterogeneity (I = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = -0.45 min (95% CI -5.89 to 4.99)).ConclusionDespite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account.Trial registrationPROSPERO (CRD42019147939).

Dataset Information

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

Publications

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

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