Jens Karmrodt

Spatial and temporal heterogeneity of ventilator-associated lung injury after surfactant depletion

Volutrauma and atelectrauma have been proposed as mechanisms of ventilator-associated lung injury, but few studies have compared their relative importance in mediating lung injury. The objective of our study was to compare the injury produced by stretch (volutrauma) vs. cyclical recruitment (atelectrauma) after surfactant depletion. In saline-lavaged rabbits, we used high tidal volume, low respiratory rate, and low positive end-expiratory pressure to produce stretch injury in nondependent lung regions and cyclical recruitment in dependent lung regions. Tidal changes in shunt fraction were assessed by measuring arterial Po(2) oscillations. After ventilating for times ranging from 0 to 6 h, lungs were excised, sectioned gravitationally, and assessed for regional injury by evaluation of edema formation, chemokine expression, upregulation of inflammatory enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung tissue interleukin-8 expression, and alveolar neutrophil accumulation progressed more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1 expression progressed more rapidly in nondependent lung regions. Temporal and regional heterogeneity of lung injury were substantial. In this surfactant depletion model of acute lung injury, cyclical recruitment produced more injury than stretch.

High-frequency oscillatory ventilation in adults with traumatic brain injury and acute respiratory distress syndrome

Background:  This study observed adverse events of rescue treatment with high‐frequency oscillatory ventilation (HFOV) in head‐injured patients with acute respiratory distress syndrome (ARDS).

Dynamic computed tomography: a novel technique to study lung aeration and atelectasis formation during experimental CPR.

OBJECTIVE To develop an image based technique to study the effect of different ventilatory strategies on lung ventilation and alveolar recruitment during cardiopulmonary resuscitation (CPR). DESIGN (1) Technical development of the following components: (a) construction of an external chest compression device, which does not interfere with CT imaging, and (b) development of a software tool to detect lung parenchyma automatically and to calculate radiological density parameters. (2) Feasibility studies: three strategies of CPR ventilation were performed and imaged in one animal each (pigs, 25 kg): volume-constant ventilation (VCV), no ventilation, or continuous airway pressure (CPAP). One minute after induction of circulatory arrest inside the CT scanner, external chest compressions started at a rate of 100 cpm, and one of the ventilation modes was initiated. After 1 min, intravenous epinephrine was added as a bolus (40 microg/kg), followed by a continuous infusion (13 microg/kg per min). Six minutes later, dynamic CT acquisitions (temporal resolution: 100 ms) commenced. Simultaneously, arterial blood gases, acid base status and haemodynamics were sampled. RESULTS Using a modified chest compression device, dynamic CT acquisitions are feasible during closed-chest CPR. In three pilot experiments with different ventilation strategies, the dedicated software tool allowed to quantify ventilated, atelectatic and over-distended fractions of total lung area. VCV showed a large amount of atelectasis, which was recruited during every respiratory cycle. No ventilation led to atelectasis to govern over 50% of the total lung area. CPAP caused less atelectasis as VCV, and no cyclic recruitment and de-recruitment phenomena were observed. CONCLUSIONS We demonstrate a novel experimental set up, which allows quantification of different lung compartments during ongoing CPR and may become useful in comparing the direct pulmonary effects of different ventilatory strategies in the settings of Basic and Advanced Cardiac Life Support.

Effect of chest compressions only during experimental basic life support on alveolar collapse and recruitment

AIM The importance of ventilatory support during cardiac arrest and basic life support is controversial. This experimental study used dynamic computed tomography (CT) to assess the effects of chest compressions only during cardiopulmonary resuscitation (CCO-CPR) on alveolar recruitment and haemodynamic parameters in porcine model of ventricular fibrillation. MATERIALS AND METHODS Twelve anaesthetized pigs (26+/-1 kg) were randomly assigned to one of the following groups: (1) intermittent positive pressure ventilation (IPPV) both during basic life support and advanced cardiac life support, or (2) CCO during basic life support and IPPV during advanced cardiac life support. Measurements were acquired at baseline prior to cardiac arrest, during basic life support, during advanced life support, and after return of spontaneous circulation (ROSC), as follows: dynamic CT series, arterial and central venous pressures, blood gases, and regional organ blood flow. The ventilated and atelectatic lung area was quantified from dynamic CT images. Differences between groups were analyzed using the Kruskal-Wallis test, and a p<0.05 was considered statistically significant. RESULTS IPPV was associated with cyclic alveolar recruitment and de-recruitment. Compared with controls, the CCO-CPR group had a significantly larger mean fractional area of atelectasis (p=0.009), and significantly lower PaO2 (p=0.002) and mean arterial pressure (p=0.023). The increase in mean atelectatic lung area observed during basic life support in the CCO-CPR group remained clinically relevant throughout the subsequent advanced cardiac life support period and following ROSC, and was associated with prolonged impaired haemodynamics. No inter-group differences in myocardial and cerebral blood flow were observed. CONCLUSION A lack of ventilation during basic life support is associated with excessive atelectasis, arterial hypoxaemia and compromised CPR haemodynamics. Moreover, these detrimental effects remain evident even after restoration of IPPV.

Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs.

IntroductionThe objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury.MethodsLung damage was induced by repeated lung lavages in seven anesthetized pigs (23–26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting.ResultsThe transpulmonary pressure increased during lung recruitment (HFOV, from 15 ± 3 mbar to 22 ± 2 mbar, P < 0.05; PCV, from 15 ± 3 mbar to 23 ± 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 ± 1 mmHg to 6 ± 3 mmHg, P < 0.05; PCV, from 2 ± 1 mmHg to 7 ± 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 ± 2 mmHg to 16 ± 2 mmHg, P < 0.05; PCV, from 13 ± 2 mmHg to 15 ± 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 ± 2 mmHg to 16 ± 2 mmHg, P < 0.05; PCV, from 15 ± 3 mmHg to 17 ± 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 ± 7 mmHg to 79 ± 9 mmHg, P < 0.05; PCV, from 91 ± 8 mmHg to 81 ± 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 ± 0.4 l/minute to 3.5 ± 0.3 l/minute, P < 0.05; PCV, from 3.8 ± 0.6 l/minute to 3.4 ± 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 ± 7 ml to 28 ± 5 ml, P < 0.05; PCV, from 31 ± 2 ml to 26 ± 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures.ConclusionA typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Ventilations-Perfusions-Verteilungen in der Lunge

ZusammenfassungDie Multiple-Inertgas-Eliminationstechnik (MIGET) stellt den Goldstandard zur Bestimmung der Ventilations- und Perfusionsverteilungen in der Lunge dar. Eine Modifikation in deren Durchführung erlaubt eine wesentlich einfachere und schnellere Handhabung, sodass diese aufwendige Methode erstmals für den klinischen Routineeinsatz geeignet erscheint. Die MIGET mithilfe der „micropore membrane inlet mass spectrometry“ (MMIMS) stellt damit eine frühere Detektion von Lungenerkrankungen und ein sensitiveres Therapiemonitoring in Aussicht.AbstractThe multiple inert gas elimination technique (MIGET) represents the gold standard for analysis of ventilation and perfusion distributions in the lung. Modification of this technique allows a much simpler sample processing and hence permits routine clinical application of this technique. MIGET using micropore membrane inlet mass spectrometry (MMIMS) might, therefore, facilitate early diagnosis of lung diseases and monitoring of therapeutic interventions in the future.

[Ventilation-perfusion distributions in the lungs. A novel technique for rapid measurement].

ZusammenfassungDie Multiple-Inertgas-Eliminationstechnik (MIGET) stellt den Goldstandard zur Bestimmung der Ventilations- und Perfusionsverteilungen in der Lunge dar. Eine Modifikation in deren Durchführung erlaubt eine wesentlich einfachere und schnellere Handhabung, sodass diese aufwendige Methode erstmals für den klinischen Routineeinsatz geeignet erscheint. Die MIGET mithilfe der „micropore membrane inlet mass spectrometry“ (MMIMS) stellt damit eine frühere Detektion von Lungenerkrankungen und ein sensitiveres Therapiemonitoring in Aussicht.AbstractThe multiple inert gas elimination technique (MIGET) represents the gold standard for analysis of ventilation and perfusion distributions in the lung. Modification of this technique allows a much simpler sample processing and hence permits routine clinical application of this technique. MIGET using micropore membrane inlet mass spectrometry (MMIMS) might, therefore, facilitate early diagnosis of lung diseases and monitoring of therapeutic interventions in the future.

Alternative protocol to initiate high-frequency oscillatory ventilation: an experimental study.

IntroductionThe objective was to study the effects of a novel lung volume optimization procedure (LVOP) using high-frequency oscillatory ventilation (HFOV) upon gas exchange, the transpulmonary pressure (TPP), and hemodynamics in a porcine model of surfactant depletion.MethodsWith institutional review board approval, the hemodynamics, blood gas analysis, TPP, and pulmonary shunt fraction were obtained in six anesthetized pigs before and after saline lung lavage. Measurements were acquired during pressure-controlled ventilation (PCV) prior to and after lung damage, and during a LVOP with HFOV. The LVOP comprised a recruitment maneuver with a continuous distending pressure (CDP) of 45 mbar for 2.5 minutes, and a stepwise decrease of the CDP (5 mbar every 5 minute) from 45 to 20 mbar. The TPP level was identified during the decrease in CDP, which assured a change of the PaO2/FIO2 ratio < 25% compared with maximum lung recruitment at CDP of 45 mbar (CDP45). Data are presented as the median (25th–75th percentile); differences between measurements are determined by Friedman repeated-measures analysis on ranks and multiple comparisons (Tukeys test). The level of significance was set at P < 0.05.ResultsThe PaO2/FiO2 ratio increased from 99.1 (56.2–128) Torr at PCV post-lavage to 621 (619.4–660.3) Torr at CDP45 (CDP45) (P < 0.031). The pulmonary shunt fraction decreased from 51.8% (49–55%) at PCV post-lavage to 1.03% (0.4–3%) at CDP45 (P < 0.05). The cardiac output and stroke volume decreased at CDP45 (P < 0.05) compared with PCV, whereas the heart rate, mean arterial pressure, and intrathoracic blood volume remained unchanged. A TPP of 25.5 (17–32) mbar was required to preserve a difference in PaO2/FIO2 ratio < 25% related to CDP45; this TPP was achieved at a CDP of 35 (25–40) mbar.ConclusionThis HFOV protocol is easy to perform, and allows a fast determination of an adequate TPP level that preserves oxygenation. Systemic hemodynamics, as a measure of safety, showed no relevant deterioration throughout the procedure.

Analysis of discrete and continuous distributions of ventilatory time constants from dynamic computed tomography.

In this study, an algorithm was developed to measure the distribution of pulmonary time constants (TCs) from dynamic computed tomography (CT) data sets during a sudden airway pressure step up. Simulations with synthetic data were performed to test the methodology as well as the influence of experimental noise. Furthermore the algorithm was applied to in vivo data. In five pigs sudden changes in airway pressure were imposed during dynamic CT acquisition in healthy lungs and in a saline lavage ARDS model. The fractional gas content in the imaged slice (FGC) was calculated by density measurements for each CT image. Temporal variations of the FGC were analysed assuming a model with a continuous distribution of exponentially decaying time constants. The simulations proved the feasibility of the method. The influence of experimental noise could be well evaluated. Analysis of the in vivo data showed that in healthy lungs ventilation processes can be more likely characterized by discrete TCs whereas in ARDS lungs continuous distributions of TCs are observed. The temporal behaviour of lung inflation and deflation can be characterized objectively using the described new methodology. This study indicates that continuous distributions of TCs reflect lung ventilation mechanics more accurately compared to discrete TCs.

Multirotations-CT und ARDS Tierexperimentelle Studien

ZusammenfassungFragestellung: Ziel dieser Arbeit war es, die alveoläre Be- und Entlüftung mittels Multirotations-CT zu untersuchen. Dabei wurden die Ergebnisse einer visuellen Auswertung mit den Flächenänderungen bereits bekannter Dichtebereiche, welche die Ventilation am besten repräsentieren, verglichen. Methodik. Es wurden Schweine vor und nach Erzeugung eines Lavage-ARDS-Modells mittels Multirotations-CT untersucht. Die visuelle Auswertung der CT-Daten wurde anhand eines Scores von Gattinoni durchgeführt. Die Ergebnisse wurden mit planimetrisch bestimmten Flächenanteilen definierter Dichtebereiche verglichen. Ergebnisse. In der gesunden Lunge zeigte die visuelle Auswertung höhere Scorewerte bei niedrigen Beatmungsdrucken mit einem deutlichen Gradienten, während bei hohen Drucken keine Verdichtungen und kein Gradient nachweisbar waren. In den ARDS-Lungen waren die Scorewerte bei niedrigen Beatmungsdrucken doppelt so hoch wie in den gesunden Lungen, während die Unterschiede zwischen In- und Exspiration bei gegebenem Beatmungsdruck gering waren. Es ergab sich eine gute Übereinstimmung zwischen dem Ausmaß der Lungenparenchymverdichtungen und der Lungendichtemessung bei unterschiedlichen Beatmungsdrucken. In der gesunden Lunge findet sich die größte Flächenzunahme während der Inspiration im Dichtebereich von −910 bis −700 HE. Im ARDS-Modell besteht die größte Flächenänderung im Dichtebereich von −910 bis −300 HE. Schlussfolgerungen. Es ist mit der Multirotations-CT möglich, relevante Dichtebereiche und Lungenkompartimente zu erkennen.AbstractPurpose: Aim of the study was to investigate alveolar inspiration and expiration using multiscan CT. Results of a visual assessment using a scoring system were compared with density ranges known to represent alveolar ventilation best. Method. Pigs were examined before and after lavage-induced ARDS. All animals were examined using dynamic multiscan CT. The visual assessment was done by a scoring system proposed by Gattinoni. The results were compared with planimetric determination of defined density ranges. Results. In the healthy lung, the visual analysis showed higher scores at lower airway pressures with a marked gradient, whereas at higher pressures neither opacities nor gradients were observed. In ARDS-lungs, the scores were double as high as in healthy lungs at low pressures. At the same time the differences between inspiration and expiration were minor. There was good correlation between lung density measurements and lung opacities under different airway pressures. In healthy lungs, the greatest area increase is found between −910 and −700 HU. The biggest area growth in the ARDS-model is observed between −910 and −300 HU. Conclusion. Dynamic multiscan CT allows for determining different ventilation-relevant lung compartments and lung density ranges.