| 1. |
- Akca, Ozan, et al.
(författare)
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WHO Needs High FIO2?
- 2017
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Ingår i: TURKISH JOURNAL OF ANAESTHESIOLOGY AND REANIMATION. - : AVES. - 2149-0937. ; 45:4, s. 181-192
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Tidskriftsartikel (refereegranskat)abstract
- World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations
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| 2. |
- 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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| 3. |
- Bergmann, Astrid, et al.
(författare)
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Data on the effects of remote ischemic preconditioning in the lungs after one-lung ventilation
- 2018
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 21, s. 441-448
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Tidskriftsartikel (refereegranskat)abstract
- This article contains data on experimental endpoints of a randomized controlled animal trial. Fourteen healthy piglets underwent mechanical ventilation including injurious one-lung ventilation (OLV), seven of them experienced four cycles of remote ischemic preconditioning (RIP) on one hind limb immediately before OLV, seven of them did not receive RIP and served as controls, in a randomized manner. The two major endpoints were (1) pulmonary damage assessed with the diffuse alveolar damage (DAD) score and (2) the inflammatory response assessed by cytokine concentrations in serum and in bronchoalveolar lavage fluids (BAL). The cytokine levels in the homogenized lung tissue samples are presented in the original article. Further interpretation and discussion of these data can be found in Bergmann et al. (in press).
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| 4. |
- Bergmann, Astrid, et al.
(författare)
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Early and late effects of remote ischemic preconditioning on spirometry and gas exchange in healthy volunteers
- 2020
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 271
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Remote ischemic preconditioning (RIP) may protect remote organs from ischemia-reperfusion-injury (IRI) in surgical and non-surgical patients. There are few data available on RIP and lung function, especially not in healthy volunteers. The null-hypothesis was tested that RIP does not have an effect on pulmonary function when applied on healthy volunteers that were breathing spontaneously and did not experience any intervention. After approval of the Ethics Committee and informed consent of the study subjects, 28 healthy non-smoking volunteers were included and randomized in either the RIP group (n = 13) or the control group (n = 15). In the RIP group, lower limb ischemia was induced by inflation of a blood pressure cuff to a pressure 20 mmHg above the systolic blood pressure. After five minutes the blood pressure cuff was released for five minutes rest. The procedure was repeated three times resulting in 40 min ischemia and reperfusion. Capillary blood samples were taken, and lung function tests were performed at baseline (T1) and 60 min (T2) and 24 h (T3) after RIP. The control group was treated in the same fashion, but the RIP procedure was replaced by a sham protocol.Results: 60 min after RIP capillary pO(2) decreased significantly and returned to baseline level after 24 h in the RIP group. This did not occur in the control group. Capillary pCO(2), variables of lung function tests and pulmonary capillary blood volume remained unchanged throughout the experiment in both groups.Conclusion: Oxygenation is impaired early after RIP which is possibly induced by transient ventilation-perfusion inequality. No late effects of RIP were observed. The null hypothesis has to be rejected that RIP has no effect on respiratory variables in healthy volunteers.
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| 5. |
- Bergmann, Astrid, et al.
(författare)
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Effect of remote ischemic preconditioning on exhaled nitric oxide concentration in piglets during and after one-lung ventilation
- 2020
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 276
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remote ischemic preconditioning (RIP) may protect target organs from ischemia - reperfusion injury, however, little is known on pulmonary effects of RIP prior to, immediately after and several hours after one-lung ventilation (OLV). The present randomized, controlled, animal experiment was undertaken to analyze these issues.METHODS: After animal ethics committee approval, twelve piglets (26 ± 2 kg) were anesthetized and randomly assigned to a control (n = 6) or to a RIP group (n = 6). For RIP, arterial perfusion of a hind limb was suspended by an inflated blood pressure cuff (200 mmHg for 5 min) and deflated for another 5 min, this was repeated four times. After intubation, mechanical ventilation (MV) was kept constant with tidal volume 10 ml/kg, inspired oxygen fraction (FIO2) 0.40, and positive end-expiratory pressure (PEEP) 5cmH2O. FIO2 was increased to 1 after RIP in the RIP group and after the sham procedure in the control group, respectively, for the time of OLV. OLV was established by left-sided bronchial blockade. After OLV, TLV was re-established until the end of the protocol. Exhaled nitric oxide (NO) was measured by ozon chemiluminiscense and ventilatory and hemodynamic variables were assessed according to the protocol.RESULTS: Hemodynamic and respiratory data were similar in both groups. Arterial pO2 was higher in the RIP group after two hours of OLV. In the control group, exhaled NO decreased during OLV and remained at low levels for the rest of the protocol. In the RIP group, exhaled NO decreased as well during OLV but returned to baseline levels when TLV was re-established.CONCLUSIONS: RIP has no effects on hemodynamic and respiratory variables in juvenile, healthy piglets. RIP improves the oxygenation after OLV and prevents the decline of exhaled NO after OLV.
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| 6. |
- Bergmann, Astrid, et al.
(författare)
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Pulmonary effects of remote ischemic preconditioning in a porcine model of ventilation-induced lung injury
- 2019
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier. - 1569-9048 .- 1878-1519. ; 259, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) may result in lung injury due to increased mechanical stress and tidal recruitment. As a result, a pulmonary inflammatory response is induced. The present randomized, controlled, animal experiment was undertaken to assess the effects of remote ischemic preconditioning (RIP) on diffuse alveolar damage and immune response after OLV.METHODS: Fourteen piglets (26 ± 2 kg) were randomized to control (n = 7) and RIP group (n = 7). For RIP, a blood pressure cuff at hind limb was inflated up to 200 mmHg for 5 min and deflated for another 5 min, this being done four times before OLV. Mechanical ventilation settings were constant throughout the experiment: VT = 10 ml/kg, FIO2 = 0.40, PEEP = 5cmH2O. OLV was performed by left-sided bronchial blockade. Number of cells was counted from BAL fluid; cytokines were assessed by immunoassays in lung tissue and serum samples. Lung tissue samples were obtained for histological analysis and assessment of diffuse alveolar damage (DAD) score.RESULTS: Hemodynamic and respiratory data were similar in both groups. Likewise, no differences in pulmonary tissue TNF-α and protein content were found, but fewer leukocytes were counted in the ventilated lung after RIP. DAD scores were high without any differences between controls and RIP. On the other hand, alveolar edema and microhemorrhage were significantly increased after RIP.CONCLUSIONS: OLV results in alveolar injury, possibly enhanced by RIP. On the other hand, RIP attenuates the immunological response and decreased alveolar leukocyte recruitment in a porcine model of OLV.
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| 7. |
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| 8. |
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| 9. |
- 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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| 10. |
- 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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| 11. |
- 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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| 12. |
- 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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| 13. |
- Kozian, Alf, et al.
(författare)
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Ventilatory Protective Strategies during Thoracic Surgery Effects of Alveolar Recruitment Maneuver and Low-tidal Volume Ventilation on Lung Density Distribution
- 2011
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 114:5, s. 1025-1035
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Tidskriftsartikel (refereegranskat)abstract
- Background: The increased tidal volume (V-T) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced V-T may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different V-T on pulmonary gas/tissue distribution are examined. Methods: Eight anesthetized piglets were mechanically ventilated (V-T = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H2O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a V-T of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. Results: The dependent lung contained atelectatic (56 +/- 10 ml), poorly aerated (183 +/- 10 ml), and normally aerated (187 +/- 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 +/- 35 vs. 526 +/- 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased(95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 +/- 2 ml; poorly aerated, 94 +/- 24 ml; normally aerated, 580 +/- 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean +/- SD.) Conclusions: The ARM improves aeration and respiratory mechanics. In contrast to OLV with high V-T, OLV with reduced V-T does not reinforce tidal recruitment, indicating decreased mechanical stress.
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| 14. |
- 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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| 15. |
- Kretzschmar, Moritz, et al.
(författare)
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Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model
- 2016
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 220, s. 88-94
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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.
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| 16. |
- 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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| 17. |
- Kretzschmar, Moritz, et al.
(författare)
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Multiple inert gas elimination technique by micropore membrane inlet mass spectrometry-a comparison with reference gas chromatography
- 2013
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 115:8, s. 1107-1118
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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.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Schilling, Thomas, 1966-, et al.
(författare)
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Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation
- 2007
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 99:3, s. 368-375
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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.
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| 22. |
- Schilling, Thomas, et al.
(författare)
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Effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients
- 2011
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 115:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery. METHODS: Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg⁻¹ · h⁻¹ propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 μg · kg⁻¹ · min⁻¹). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg ideal body weight, a peak airway pressure lower than 30 cm H₂O, a respiratory rate adjusted to a Paco2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays. RESULTS: Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-α, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml⁻¹). Interleukin-1β was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible. CONCLUSIONS: OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.
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| 23. |
- Schilling, Thomas, et al.
(författare)
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In reply :
- 2012
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 116:2, s. 492-493
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Schilling, Thomas, 1966-
(författare)
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The Immune Response to One-Lung Ventilation : Clinical and Experimental Studies
- 2009
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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.
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| 25. |
- Schilling, Thomas, et al.
(författare)
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The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery
- 2005
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Ingår i: Anesthesia and Analgesia. - : International Anesthesia Research Society. - 0003-2999 .- 1526-7598. ; 101:4, s. 957-965
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. IMPLICATIONS: Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.
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| 26. |
- Bergmann, Astrid, 1972-
(författare)
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Remote Ischemic Preconditioning and its Effects on the Respiratory System
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mechanical ventilation in itself can lead to pulmonary damage, and one-lung ventilation (OLV), necessary for thoracic surgery, accentuates this injury. Remote ischemic preconditioning (RIP) is a potential tool to reduce lung injury after mechanical ventilation, including OLV. However, current data on pulmonary RIP-effects are contradictory. Therefore, the overall purpose of this Ph.D. project was to assess the effects of RIP on the respiratory system. In Study I, in healthy spontaneously breathing volunteers, oxygenation was impaired early after RIP, which was possibly induced by transient ventilation-perfusion inequality. Studies II, III, and IV were performed in a porcine OLV model. In Study II, we found that RIP possibly enhances alveolar injury, but attenuates the immune response. In Study III, we confirmed that an immune response to RIP takes place, which shows a different time pattern in each cytokine, depending on the site of measurement as well. In Study IV, we studied the porcine model for eight hours and found that RIP improved oxygenation after two hours of OLV and impeded the decline of exhaled nitric oxide (NO) during and after OLV. These findings indicate that RIP mitigates hypoxic pulmonary vasoconstriction (HPV).In summary, RIP has a complex effect on the respiratory system, which partly explains the previous contradictory findings.
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| 27. |
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| 28. |
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| 29. |
- Hachenberg, Tomas, et al.
(författare)
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Physiologie des respiratorischen systems
- 2010. - 1:2
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Ingår i: Anästhesie und Intensivtherapie in der Thoraxkirurgie. - Stuttgart : Thieme. - 9783131487711 - 3131487712 ; , s. 13-22
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- 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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| 31. |
- Kretzschmar, Moritz A., et al.
(författare)
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Thoracic anaesthesia 2016
- 2016
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Ingår i: Current Opinion in Anaesthesiology. - 0952-7907 .- 1473-6500. ; 29:1, s. 1-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Kretzschmar, Moritz A., et al.
(författare)
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Thoracic anesthesia
- 2015
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Ingår i: Current Opinion in Anaesthesiology. - 0952-7907 .- 1473-6500. ; 28:1, s. 1-1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 33. |
- Schilling, Thomas, et al.
(författare)
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The immune response to one-lung-ventilation is not affected by repeated alveolar recruitment manoeuvres in pigs
- 2013
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Ingår i: Minerva Anestesiologica. - 0375-9393 .- 1827-1596. ; 79:6, s. 590-603
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Tidskriftsartikel (refereegranskat)abstract
- Background. Acute lung injury after thoracic surgery relates to alveolar inflammation induced by one-lung ventilation (OLV) and surgical manipulation. However, alveolar recruitment manoeuvres (ARM), conventional ventilation, and airway manipulation may increase alveolar trauma. This study evaluates pulmonary immune effects of these co-factors in a porcine model. Methods. Twenty-two piglets (27.3 kg) were randomised to spontaneous breathing (N.=4), two-lung ventilation (TLV, N.=6), OLV with propofol (6 mg/kg/h, N.=6) or desflurane anesthesia (1MAC, N.=6). Mechanical ventilation settings were constant throughout the experiment: V-T=10 mL/kg, F1O2=0.4, PEEP=5 cmH(2)O. OLV was performed by left-sided bronchial blockade. Thoracic surgery was simulated for 60 min. ARM (airway pressure of 40 mbar for 10 s) was applied before and after each airway manipulation. Cytokines and mRNA-expression were assessed by immunoassays and semi-quantitative RT-PCR in alveolar lavage fluids, serum and tissue samples prior to and after OLV (TLV in controls). Results. Repetitive ARM and TLV induced no significant proinflammatory effects. OLV enhanced cytokine release but less with desflurane inhalation than propofol infusion (median (IQR) [pg/mL], dependent lung): Interleukin-8: TLV 44 (17) to 68 (35), propofol 82 (17) to 494 (231), desflurane 89 (30) to 282 (44). Likewise, serum cytokines were different: tumour necrosis factor-a: TLV 37 (13) to 62 (7), propofol 55 (39) to 94 (60), desflurane 43 (33) to 41 (25). Expression of interleukin-8-mRNA increased after OLV, but mRNA expression was not modulated by anesthetics. Conclusion. ARM, standard TLV and repetitive BAL do not additionally contribute to lung injury resulting from OLV for thoracic surgery in healthy porcine lungs. OLV induces expression of interleukin-8-mRNA in alveolar cells, which is not modulated by different anesthetic drugs.
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| 34. |
- Strang, Christof M., et al.
(författare)
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Development of atelectasis and arterial to end-tidal PCO2-difference in a porcine model of pneumoperitoneum
- 2009
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 103:2, s. 298-303
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intraperitoneal insufflation of carbon dioxide (CO2) may promote collapse of dependent lung regions. The present study was undertaken to study the effects of CO2-pneumoperitoneum (CO2-PP) on atelectasis formation, arterial oxygenation, and arterial to end-tidal PCO2-gradient (Pa-E'(CO2)). METHODS: Fifteen anaesthetized pigs [mean body weight 28 (SD 2) kg] were studied. Spiral computed tomography (CT) scans were obtained for analysis of lung tissue density. In Group 1 (n=5) mechanical ventilation (V(T)=10 ml kg (-1), FI(O2)=0.5) was applied, in Group 2 (n=5) FI(O2) was increased for 30 min to 1.0 and in Group 3 (n=5) negative airway pressure was applied for 20 s in order to enhance development of atelectasis. Cardiopulmonary and CT data were obtained before, 10, and 90 min after induction of CO2-PP at an abdominal pressure of 12 mmHg. RESULTS: Before CO2-PP, in Group 1 non-aerated tissue on CT scans was 1 (1)%, in Group 2 3 (2)% (P<0.05, compared with Group 1), and in Group 3 7 (3)% (P<0.05, compared with Group 1 and Group 2). CO2-PP significantly increased atelectasis in all groups. PaO2/FI(O2) fell and venous admixture ('shunt') increased in proportion to atelectasis during anaesthesia but CO2-PP had a varying effect on PaO2/FI(O2) and shunt. Thus, no correlation was seen between atelectasis and PaO2/FI(O2) or shunt when all data before and during CO2-PP were pooled. Pa-E'(CO2), on the other hand correlated strongly with the amount of atelectasis (r2=0.92). CONCLUSIONS: Development of atelectasis during anaesthesia and PP may be estimated by an increased Pa-E'(CO2).
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