| 1. |
- Baumgardner, James E., et al.
(författare)
-
Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics
- 2021
-
Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 135:6, s. 1042-1054
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Kinetics of the uptake of inhaled anesthetics have been well studied, but the kinetics of elimination might be of more practical importance. The objective of the authors' study was to assess the effect of the overall ventilation/perfusion ratio (V-A/Q), for normal lungs, on elimination kinetics of desflurane and sevoflurane.Methods: The authors developed a mathematical model of inhaled anesthetic elimination that explicitly relates the terminal washout time constant to the global lung V-A/Q ratio. Assumptions and results of the model were tested with experimental data from a recent study, where desflurane and sevoflurane elimination were observed for three different V-A/Q conditions: normal, low, and high.Results: The mathematical model predicts that the global V-A/Q ratio, for normal lungs, modifies the time constant for tissue anesthetic washout throughout the entire elimination. For all three V-A/Q conditions, the ratio of arterial to mixed venous anesthetic partial pressure P-art/P-mv reached a constant value after 5 min of elimination, as predicted by the retention equation. The time constant corrected for incomplete lung clearance was a better predictor of late-stage kinetics than the intrinsic tissue time constant.Conclusions: In addition to the well-known role of the lungs in the early phases of inhaled anesthetic washout, the lungs play a long-overlooked role in modulating the kinetics of tissue washout during the later stages of inhaled anesthetic elimination. The V-A/Q ratio influences the kinetics of desflurane and sevoflurane elimination throughout the entire elimination, with more pronounced slowing of tissue washout at lower V-A/Q ratios.
|
|
| 2. |
- Baumgardner, James E., et al.
(författare)
-
Ventilation/perfusion distributions revisited
- 2016
-
Ingår i: Current Opinion in Anaesthesiology. - 0952-7907 .- 1473-6500. ; 29:1, s. 2-7
-
Forskningsöversikt (refereegranskat)abstract
- Purpose of reviewA major cause of hypoxemia in anesthesia is ventilation-perfusion (V-A/Q) mismatch. With more advanced surgery and an aging population, monitoring of V-A/Q is of increasing importance.Recent findingsThe classic multiple inert gas elimination technique has been simplified with a new approach based on mass spectrometry. V-A/Q distributions can also be measured, at the bedside, by varying inspired oxygen concentration. MRI, 3-dimensional single photon emission computed tomography, positron emission tomography, and electrical impedance tomography enable imaging of perfusion and ventilation, and in some of the techniques also the distribution of inflammation. One-lung ventilation with thoracoscopy and capnothorax require careful monitoring of V-A/Q, made possible bedside by electrical impedance tomography. Carbon dioxide, but not air, for pneumoperitoneum enhances shift of perfusion to ventilated regions. Ventilatory support during cardiopulmonary resuscitation causes less V-A/Q mismatch when inspired oxygen concentrations are lower. Mechanisms of redistribution of lung blood flow by inhaled nitric oxide include endothelin-mediated vasoconstriction in collapsed lung regions.SummaryMethods are continuously developing to simplify measurement of V-A/Q and also to relate V-A/Q to inflammation. The recording of V-A/Q has helped to explain important aspects of gas exchange in thoracic anesthesiology and in intensive care medicine.
|
|
| 3. |
- Kozian, Alf, 1969-, et al.
(författare)
-
Effects of methacholine infusion on desflurane pharmacokinetics in piglets
- 2015
-
Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 5, s. 939-947
-
Tidskriftsartikel (refereegranskat)abstract
- The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and pulmonary perfusion in relation to the V.A/Q. compartments, data of logSDQ̇ and logSDV̇ (the second moments describing global dispersion, i.e. heterogeneity of distribution) were estimated prior to and after MCh infusion. The uptake and elimination of desflurane was determined by MMIMS.
|
|
| 4. |
- Kretzschmar, Moritz, et al.
(författare)
-
Arterial and Mixed Venous Kinetics of Desflurane and Sevoflurane, Administered Simultaneously, at Three Different Global Ventilation to Perfusion Ratios in Piglets with Normal Lungs
- 2021
-
Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 135:6, s. 1027-1041
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Previous studies have established the role of various tissue compartments in the kinetics of inhaled anesthetic uptake and elimination. The role of normal lungs in inhaled anesthetic kinetics is less understood. In juvenile pigs with normal lungs, the authors measured desflurane and sevoflurane washin and washout kinetics at three different ratios of alveolar minute ventilation to cardiac output value. The main hypothesis was that the ventilation/perfusion ratio (V-A/Q) of normal lungs influences the kinetics of inhaled anesthetics.Methods: Seven healthy pigs were anesthetized with intravenous anesthetics and mechanically ventilated. Each animal was studied under three different V-A/Q conditions: normal, low, and high. For each V-A/Q condition, desflurane and sevoflurane were administered at a constant, subanesthetic inspired partial pressure (0.15 volume% for sevoflurane and 0.5 volume% for desflurane) for 45 min. Pulmonary arterial and systemic arterial blood samples were collected at eight time points during uptake, and then at these same times during elimination, for measurement of desflurane and sevoflurane partial pressures. The authors also assessed the effect of V-A/Q on paired differences in arterial and mixed venous partial pressures.Results: For desflurane washin, the scaled arterial partial pressure differences between 5 and 0 min were 0.70 +/- 0.10, 0.93 +/- 0.08, and 0.82 +/- 0.07 for the low, normal, and high V-A/Q conditions (means, 95% CI). Equivalent measurements for sevoflurane were 0.55 +/- 0.06, 0.77 +/- 0.04, and 0.75 +/- 0.08. For desflurane washout, the scaled arterial partial pressure differences between 0 and 5 min were 0.76 +/- 0.04, 0.88 +/- 0.02, and 0.92 +/- 0.01 for the low, normal, and high V-A/Q conditions. Equivalent measurements for sevoflurane were 0.79 +/- 0.05, 0.85 +/- 0.03, and 0.90 +/- 0.03.Conclusions: Kinetics of inhaled anesthetic washin and washout are substantially altered by changes in the global V-A/Q ratio for normal lungs.
|
|
| 5. |
- Kretzschmar, Moritz, et al.
(författare)
-
Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model
- 2016
-
Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 220, s. 88-94
-
Tidskriftsartikel (refereegranskat)abstract
- Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (V̇A/Q̇) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100μg/ml, n=6) increased respiratory resistance, impaired V̇A/Q̇ distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5min vs. 1.1min, to P90: 4.0min vs. 14.8min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous V̇A/Q̇ distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients.
|
|
| 6. |
- Kretzschmar, Moritz, et al.
(författare)
-
Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane
- 2017
-
Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 127:5, s. 800-812
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increasing numbers of patients with obstructive lung diseases need anesthesia for surgery. These conditions are associated with pulmonary ventilation/perfusion (VA/Q) mismatch affecting kinetics of volatile anesthetics. Pure shunt might delay uptake of less soluble anesthetic agents but other forms of VA/Q scatter have not yet been examined. Volatile anesthetics with higher blood solubility would be less affected by VA/Q mismatch. We therefore compared uptake and elimination of higher soluble isoflurane and less soluble desflurane in a piglet model.METHODS: Juvenile piglets (26.7 ± 1.5 kg) received either isoflurane (n = 7) or desflurane (n = 7). Arterial and mixed venous blood samples were obtained during wash-in and wash-out of volatile anesthetics before and during bronchoconstriction by methacholine inhalation (100 μg/ml). Total uptake and elimination were calculated based on partial pressure measurements by micropore membrane inlet mass spectrometry and literature-derived partition coefficients and assumed end-expired to arterial gradients to be negligible. VA/Q distribution was assessed by the multiple inert gas elimination technique.RESULTS: Before methacholine inhalation, isoflurane arterial partial pressures reached 90% of final plateau within 16 min and decreased to 10% after 28 min. By methacholine nebulization, arterial uptake and elimination delayed to 35 and 44 min. Desflurane needed 4 min during wash-in and 6 min during wash-out, but with bronchoconstriction 90% of both uptake and elimination was reached within 15 min.CONCLUSIONS: Inhaled methacholine induced bronchoconstriction and inhomogeneous VA/Q distribution. Solubility of inhalational anesthetics significantly influenced pharmacokinetics: higher soluble isoflurane is less affected than fairly insoluble desflurane, indicating different uptake and elimination during bronchoconstriction.
|
|
| 7. |
- Kretzschmar, Moritz, et al.
(författare)
-
Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry-a comparison with reference gas chromatography
- 2013
-
Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:8, s. 1107-1118
-
Tidskriftsartikel (refereegranskat)abstract
- The mismatching of alveolar ventilation and perfusion (V-A/Q) is the major determinant of impaired gas exchange. The gold standard for measuring V-A/Q distributions is based on measurements of the elimination and retention of infused inert gases. Conventional multiple inert gas elimination technique (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures, which requires tonometry of blood samples with a gas that can then be injected into the chromatograph. The method is laborious and requires meticulous care. A new technique based on micropore membrane inlet mass spectrometry (MMIMS) facilitates the handling of blood and gas samples and provides nearly real-time analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3 with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left lower lobe ventilation. The different protocols ensured a large range of normal and abnormal V-A/Q distributions. Eight inert gases (SF6, krypton, ethane, cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused; six of these gases were measured with MMIMS, and six were measured with GC. We found close agreement of retention and excretion of the gases and the constructed V-A/Q distributions between GC and MMIMS, and predicted Pa-O2 from both methods compared well with measured Pa-O2. V-A/Q by GC produced more widely dispersed modes than MMIMS, explained in part by differences in the algorithms used to calculate V-A/Q distributions. In conclusion, MMIMS enables faster measurement of V-A/Q, is less demanding than GC, and produces comparable results.
|
|
