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      Comparison of bispectral index-guided and fixed-gas concentration techniques in desflurane and remifentanil anesthesia: A randomized controlled trial

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          Abstract

          Anesthesia with desflurane and remifentanil can be maintained with either fixed or titrated desflurane concentration. We hypothesized that the fixed-gas concentration (FG) method would reduce the number of anesthetic titrations without hypnotic and hemodynamic instability compared to the bispectral index (BIS)-guided (BG) method. Forty-eight patients were randomly allocated to the FG or BG groups. In the FG group, desflurane vaporizer setting was fixed at 1 age-corrected minimum alveolar concentration (MAC). In the BG group, desflurane was titrated to target a BIS level at 50. Remifentanil was titrated to maintain a systolic arterial pressure (SAP) of 120 mmHg in both groups. Our primary endpoint was the hypnotic stability measured by the wobble of BIS in performance analysis, and the secondary endpoints included the wobble of SAP, mean BIS value during surgery, and the number of anesthetic titrations. The BIS in the FG group showed significantly less wobble (3.9 ± 1.1% vs 5.5 ± 1.5%, P <0.001) but lower value (33 ± 6 vs 46 ± 7, P <0.001) than BG group. The wobble of SAP showed no difference between groups [median (inter-quartile range), 5.0 (4.1–7.5)% vs 5.2 (4.2–8.3)%, P = 0.557]. The numbers of anesthetic titrations in the FG group were significantly lower than the BG group (0 ± 0 vs 8 ± 5, P<0.001 for desflurane, 13 ± 13 vs 22 ± 17, P = 0.047 for remifentanil). Less wobble in BIS and reduced anesthetic titration without hemodynamic instability during the FG technique may be practical in balanced anesthesia using desflurane and remifentanil anesthesia.

          Clinical trial: This study was registered at ClinicalTrials.gov ( NCT02283866).

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          G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

          G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of the t, F, and chi2 test families. In addition, it includes power analyses for z tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
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            Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam.

            The Observer's Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subject's level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p less than 0.05) for all three treatment levels at both test periods.
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              Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development.

              Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil. Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of 1 to 8 micrograms.kg-1.min-1 for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concentration. The electroencephalogram was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an additional 15 healthy participants ages 41 to 84 y. The parameters for the simple three-compartment pharmacokinetic model were V1 = 4.98 l, V2 = 9.01 l, V3 = 6.54 l, Cl1 = 2.46 l/min, Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 y, V1 and Cl1 decreased by approximately 25% and 33%, respectively. The parameters for the simple sigmoid Emax pharmacodynamic model were Ke0 = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz, EC50 = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC50 and Ke0, with both decreasing by approximately 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively. This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter.
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                Author and article information

                Contributors
                Role: Data curationRole: ValidationRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curation
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 November 2020
                2020
                : 15
                : 11
                : e0241828
                Affiliations
                [001]Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea
                Cleveland Clinic, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-0048-7958
                Article
                PONE-D-19-32269
                10.1371/journal.pone.0241828
                7644031
                33152029
                ca5078d7-11d8-4596-9204-9d89f1113e04
                © 2020 Yang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 December 2019
                : 20 October 2020
                Page count
                Figures: 4, Tables: 2, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Anesthesiology
                Anesthesia
                Medicine and Health Sciences
                Pharmaceutics
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                Pharmacology
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                Anesthetics
                Medicine and Health Sciences
                Pain Management
                Anesthetics
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                Surgical and Invasive Medical Procedures
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                Vascular Medicine
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                Hematology
                Hemodynamics
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                Anesthesiology
                Anesthesiology Monitoring
                Medicine and Health Sciences
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                General Anesthesia
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                Pharmaceutics
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                Custom metadata
                The anonymized dataset of the current study is available (supporting information file 3).

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