| 1. |
- Baumgardner, James E., et al.
(författare)
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Effect of Global Ventilation to Perfusion Ratio, for Normal Lungs, on Desflurane and Sevoflurane Elimination Kinetics
- 2021
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Ingår i: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 135:6, s. 1042-1054
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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.
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| 4. |
- Kozian, Alf, 1969-, et al.
(författare)
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Effects of methacholine infusion on desflurane pharmacokinetics in piglets
- 2015
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 5, s. 939-947
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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.
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| 5. |
- Kozian, Alf, 1969-, et al.
(författare)
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Increased Alveolar Damage after Mechanical Ventilation in a Porcine Model of Thoracic Surgery
- 2010
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 24:4, s. 617-623
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Mechanical stress during one-lung ventilation (OLV) results in lung injury. This experiment compares effects of mechanical ventilation, OLV and surgical manipulation on diffuse alveolar damage (DAD) after application of different anesthetic regimes. Design: Prospective, randomized, controlled, blinded animal experiment. Setting: University hospital. Objects: Twenty-one piglets. Interventions: Animals (27.5kg) were randomized into four groups: spontaneous breathing (SB, n=3); two-lung ventilation (TLV, n=6); OLV during desflurane (n=6) and propofol anesthesia (n=6). SB pigs were killed after induction of anesthesia. Lung tissue samples were analyzed to obtain reference values for alveolar damage. TLV pigs underwent standard TLV (VT=10ml/kg, FIO2=0.40, PEEP=5cmH2O). In OLV pigs, after lung separation by a bronchial blocker, OLV (VT=10ml/kg) and thoracic surgery were performed. After the procedure the pigs were killed. Lung tissue samples were harvested for histological examination. Lung injury was quantified by DAD score; sequestration of leukocytes was assessed by recruitment of CD45+-cells into the lungs. Main Results: TLV resulted in increased DAD scores in both lungs (TLV vs. SB: 6.9 vs. 2.7; p<0.05); the number of CD45+-cells was not increased (TLV vs. SB: 8.7 vs. 5.0 cells/view). OLV and surgical manipulation increased DAD and leukocyte sequestration without differences between the ventilated and manipulated lungs. Leukocyte recruitment was not differently affected by the anesthetic regimen (propofol vs. desflurane: CD45+-cells/view: 13.5 vs. 11.3). Conclusions: TLV resulted in increased DAD scores in the lungs as compared with SB. OLV and thoracic surgery further increased lung injury and leukocyte recruitment independently of the administration of propofol or desflurane anesthesia.
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| 6. |
- Kozian, Alf, 1969-, et al.
(författare)
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Lung computed tomography density distribution in a porcine model of one-lung ventilation
- 2009
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 102:4, s. 551-560
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) exposes the dependent lung to increased mechanical stress which may affect the postoperative course. This study evaluates regional pulmonary gas/tissue distribution in a porcine model of OLV. METHODS: Nine anaesthetized and mechanically ventilated (V(T)=10 ml kg(-1), FI(O(2))=0.40, PEEP=5 cm H(2)O) pigs were studied. After lung separation by an endobronchial blocker, lateral thoracotomy and OLV were performed in six pigs. Three animals served as controls. Static end-expiratory and end-inspiratory spiral computed tomography (CT) scans were done before, during, and after OLV and at corresponding times in controls. CT images were analysed by defined regions of interest and summarized voxels were classified by defined lung X-ray density intervals (atelectasis, poorly aerated, normally aerated, and overaerated). RESULTS: Dependent lungs contained poorly aerated regions and atelectasis with a significant tidal recruitment during conventional two-lung ventilation (TLV) before OLV (expiration vs inspiration: atelectasis 29% vs 14%; poorly aerated 66% vs 44%; normally aerated 4% vs 41% of the dependent lung volume, P<0.05). During OLV (V(T)=10 ml kg(-1)), cyclic recruitment was increased. The density spectrum of the ventilated lung changed from consolidation to aeration (expiration vs inspiration: atelectasis 10% vs 2%; poorly aerated 71% vs 18%; normally aerated 19% vs 79%, P<0.05). After OLV, increased aeration remained with less atelectasis and poorly aerated regions. Lung density distribution in the non-dependent lung of OLV pigs was unaltered after the period of complete lung collapse. CONCLUSIONS: Cyclic tidal recruitment during OLV in pigs was associated with a persistent increase of aeration in the dependent lung.
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| 7. |
- Kozian, Alf, 1969-, et al.
(författare)
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One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung : an experimental study
- 2008
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 100:4, s. 549-559
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique [single-photon emission computed tomography (SPECT)] and relates these findings to lung histopathology after OLV. METHODS: Eleven anaesthetized and ventilated pigs (V(T)=10 ml kg(-1), Fio2=0.40, PEEP=5 cm H2O) were studied. After lung separation, OLV and thoracotomy were performed in seven pigs (OLV group). During OLV and in a two-lung ventilation (TLV), control group (n=4) ventilation settings remained unchanged. SPECT with (81m)Kr (ventilation) and (99m)Tc-labelled macro-aggregated albumin (perfusion) was performed before, during, and 90 min after OLV/TLV. Finally, lung tissue samples were harvested and examined for alveolar damage. RESULTS: OLV affected ventilation and haemodynamic variables, but there were no differences between the OLV group and the control group before and after OLV/TLV. SPECT revealed an increase of perfusion in the dependent lung compared with baseline (49-56%), and a corresponding reduction of perfusion (51-44%) in non-dependent lungs after OLV. No perfusion changes were observed in the control group. This resulted in increased low V/Q regions and a shift of V/Q areas to 0.3-0.5 (10(-0.5)-10(-0.3)) in dependent lungs of OLV pigs and was associated with an increased diffuse alveolar damage score. CONCLUSIONS: OLV in pigs results in a substantial V/Q mismatch, hyperperfusion, and alveolar damage in the dependent lung and may thus contribute to gas exchange impairment after thoracic surgery.
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| 8. |
- Kozian, Alf, 1969-
(författare)
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Pathophysiological and Histomorphological Effects of One-Lung Ventilation in the Porcine Lung
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Thoracic surgical procedures require partial or complete airway separation and the opportunity to exclude one lung from ventilation (one-lung ventilation, OLV). OLV is commonly associated with profound pathophysiological changes that may affect the postoperative outcome. It is injurious in terms of increased mechanical stress including alveolar cell stretch and overdistension, shear forces secondary to repeated tidal collapse and reopening of alveolar units and compression of alveolar vessels. Ventilation and perfusion distribution may thus be affected during and after OLV. The present studies investigated the influence of OLV on ventilation and perfusion distribution, on the gas/tissue distribution and on the lung histomorphology in a pig model of thoracic surgery.Anaesthetised and mechanically ventilated piglets were examined. The ventilation and perfusion distribution within the lungs was assessed by single photon emission computed tomography. Computed tomography was used to establish the effects of OLV on dependent lung gas/tissue distribution. The pulmonary histopathology of pigs undergoing OLV and thoracic surgery was compared with that of two-lung ventilation (TLV) and spontaneous breathing.OLV induced hyperperfusion and significant V/Q mismatch in the ventilated lung persistent in the postoperative course. It increased cyclic tidal recruitment that was associated with a persistent increase of gas content in the ventilated lung. OLV and thoracic surgery as well resulted in alveolar damage. In the present model of OLV and thoracic surgery, alveolar recruitment manoeuvre (ARM) and protective ventilation approach using low tidal volume preserved the ventilated lung density distribution and did not aggravate cyclic recruitment of alveoli in the ventilated lung.In conclusion, the present model established significant alveolar damage in response to OLV and thoracic surgery. Lung injury could be related to the profound pathophysiological consequences of OLV including hyperperfusion, ventilation/perfusion mismatch and increased tidal recruitment of lung tissue in the dependent, ventilated lung. These mechanisms may contribute to the increased susceptibility for respiratory complications in patients undergoing thoracic surgery. A protective approach including sufficient ARM, application of PEEP, and the use of lower tidal volumes may prevent the ventilated lung from deleterious consequences of OLV.
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| 9. |
- Kretzschmar, Moritz, et al.
(författare)
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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
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Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 135:6, s. 1027-1041
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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.
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| 10. |
- Kretzschmar, Moritz, et al.
(författare)
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Effect of Bronchoconstriction-induced Ventilation-Perfusion Mismatch on Uptake and Elimination of Isoflurane and Desflurane
- 2017
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 127:5, s. 800-812
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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.
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