| 1. |
- 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.
|
|
| 2. |
- 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.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Kozian, Alf, 1969-, et al.
(författare)
-
Increased Alveolar Damage after Mechanical Ventilation in a Porcine Model of Thoracic Surgery
- 2010
-
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 24:4, s. 617-623
-
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.
|
|
| 6. |
- Kozian, Alf, 1969-, et al.
(författare)
-
One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung : an experimental study
- 2008
-
Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 100:4, s. 549-559
-
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.
|
|
| 7. |
- 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.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Schilling, Thomas, 1966-, et al.
(författare)
-
Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation
- 2007
-
Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 99:3, s. 368-375
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) induces a pro-inflammatory response including cytokine release and leucocyte recruitment in the ventilated lung. Whether volatile or i.v. anaesthetics differentially modulate the alveolar inflammatory response to OLV is unclear. METHODS: Thirty patients, ASA II or III, undergoing open thoracic surgery were randomized to receive either propofol 4 mg kg(-1) h(-1) (n = 15) or 1 MAC desflurane in air (n = 15) during thoracic surgery. Analgesia was provided by i.v. infusion of remifentanil (0.25 microg kg(-1) min(-1)) in both groups. The patients were mechanically ventilated according to a standard protocol during two-lung ventilation and OLV. Fibre optic bronchoalveolar lavage (BAL) of the ventilated lung was performed before and after OLV and 2 h postoperatively. Alveolar cells, protein, tumour necrosis factor alpha (TNFalpha), interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN) elastase were determined in the BAL fluid. Data were analysed by parametric or non-parametric tests, as indicated. RESULTS: In both groups, an increase in pro-inflammatory markers was found after OLV and 2 h postoperatively; however, the fraction of alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05) was significantly higher in the propofol group compared with the desflurane group. The time courses of alveolar elastase, IL-8, and IL-10 differed between groups, and alveolar TNFalpha (7.4 vs 3.1 pg ml(-1), P < 0.05) and sICAM-1 (52.3 vs 26.3 ng ml(-1), P < 0.05) were significantly higher in the propofol group. CONCLUSIONS: These data indicate that pro-inflammatory reactions during OLV were influenced by the type of general anaesthesia. Different patterns of alveolar cytokines may be a result of increased granulocyte recruitment during propofol anaesthesia.
|
|
| 11. |
- Schilling, Thomas, 1966-
(författare)
-
The Immune Response to One-Lung Ventilation : Clinical and Experimental Studies
- 2009
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One-lung ventilation (OLV) as an established procedure during thoracic surgery may be injurious in terms of increased mechanical stress characterised by alveolar cell stretch and overdistension, increased cyclic tidal recruitment of alveolar units, compression of alveolar vessels and increased pulmonary vascular resistance. This may result in ventilation-induced lung injury with pro-inflammatory cytokine production, leukocyte recruitment and neutrophil-dependent tissue destruction. Despite the consequences of delivering the whole tidal volume (VT) to only a single lung, relatively high VT are used during OLV to maintain arterial oxygenation and carbon dioxide elimination. However, this may increase mechanical stress in the dependent lung and may aggravate alveolar injury. There is a lack of data on the alveolar immune consequences of OLV. Therefore, the present studies investigate the epithelial damage and pro-inflammatory response induced by mechanical ventilation and OLV. OLV induced pulmonary injury, but alveolar damage in the ventilated lung decreased by reduction of the tidal volume in patients scheduled for thoracic surgery (study I). The use of the volatile anaesthetic desflurane in OLV patients attenuated the OLV-induced alveolar immune response (study II). Furthermore, an experimental model of thoracic surgery was established to investigate the systemic and pulmonary consequences of OLV and thoracic surgery in comparison with the effects of conventional two-lung ventilation and spontaneous breathing. The experimental data indicate that beside the pulmonary immune response volatile anaesthetics have also modulated the plasma concentrations of cytokines during and after OLV (study III). In contrast, OLV and thoracic surgery increased the expression of pro-inflammatory mRNA in BAL cells and lung tissue samples. General anaesthesia did not affect this response (study 4). The results of the present studies indicate that OLV and thoracic surgery may be injurious to the lung tissue to a similar degree. The recruitment and activation of alveolar granulocytes characterise the alveolar damage. The administration of different anaesthetics modulates the activation of alveolar cells, specified by decreased inflammatory mediator release in subjects that receive desflurane anaesthesia, which does not affect the expression of cytokine mRNA in alveolar cells and lung tissue samples.
|
|
