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BACKGROUND Mechanical ventilation with oxygen is life-saving, however, may result in hyperoxia. The aim was to analyse the incidence and duration of hyperoxia burden and related in-hospital mortality in critically ill patients. METHODS Patients of all ages admitted to intensive care units (ICUs) and with mechanical ventilation for at least seven consecutive days were included in this single centre retrospective medical record audit. The main outcome measure was time-weighted arterial partial pressure of oxygen (PaO2 ) over 7 days. Logistic regression for association with in-hospital mortality and propensity score matching was performed. RESULTS In total, 20,889 arterial blood gases of 419 patients were analysed. Time-weighted mean PaO2 was 14.0 ± 2.4 kPa. Time-weighted mean FiO2 was 49.2 ± 12.1%. Seventy-six (18.1%) patients showed continuous hyperoxia exposure, defined as time-weighted mean PaO2 > 16 kPa. Duration of hyperoxia, hypoxia (PaO2 < 8 kPa) and normoxia (PaO2 8-16 kPa) were 37.9 ± 31.0 h (23.7%), 4.9 ± 9.5 h (3.1%), and 116.8 ± 29.6 h (73.2%). Hyperoxia occurred especially at low to moderate FiO2 in patients of first and second age quartiles (1-57 years) with smaller SAPS2 score. In-hospital mortality of patients with hyperoxia (32.9%) or normoxia did not differ (35.9%; P = 0.691). Conditional logistic regression showed no association between hyperoxia and in-hospital mortality (OR 1.46; 95%CI 0.72-2.96; P = 0.29). CONCLUSION Substantial hyperoxia burden was observed in ICU patients. Young patients with less comorbidities showed hyperoxic episodes more often, especially with lower FiO2 . Hyperoxia during 7 days of mechanical ventilation did not correlate to increased in-hospital mortality.

Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

BACKGROUND Perioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs. OBJECTIVE Our primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions. DESIGN In-vitro cell culture study. SETTING Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014. CELLS HUVECs were isolated from fresh umbilical cords. INTERVENTIONS HUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor. MAIN OUTCOME MEASURES Cell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways. RESULTS Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death-associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5' AMP-activated protein kinases 1/2. CONCLUSION Continuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury. TRIAL REGISTRATION This in-vitro study was not registered in a database.

Background During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA/Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA/Q under CPR conditions in a pig model. Methods Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. Results MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R2 = 0.96, n = 21 for baseline; R2 = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA/Q ratios to the high VA/Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA/Q. Return of spontaneous circulation were achieved in 52% of the animals. Conclusions VA/Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA/Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA/Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA/Q ratio.

BACKGROUND Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown, however, if these PaO(2) oscillations are transmitted to the microcirculation. The present study investigates if PaO(2) oscillations can be detected in the pig buccal mucosa microcirculation. METHODS Respiratory failure was induced by surfactant depletion in seven pigs. PaO(2) oscillations caused by cyclic recruitment and derecruitment were measured in the thoracic aorta by fast fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation, haemoglobin amount and blood flow in the buccal mucosa microcirculation were determined by combined fast white light spectrometry and laser Doppler flowmetry additionally to systolic arterial pressure. Measurements were performed during baseline conditions and during cyclic recruitment and derecruitment. RESULTS Measurements remained stable during baseline. Respiratory-dependent oscillations occurred in the systemic circulation [PaO(2) oscillations 92 (69-172) mmHg; systolic arterial pressure oscillations 33 (13-35) %] and were related to the respiratory rate (5.0 ± 0.2/min) as confirmed by Fourier analysis. Synchronised oscillations were detected to the pig buccal mucosa microcirculation [haemoglobin oxygen saturation oscillations 3.4 (2.7-4.9) %; haemoglobin amount oscillations 8.5 (2.3-13.3) %; blood flow oscillations 66 (18-87) %]. The delay between PaO(2) -\ and microcirculatory oxygen oscillations was 7.2 ± 2.8 s. CONCLUSION The present study suggests that PaO(2) oscillations caused by cyclic recruitment and derecruitment were transmitted to the buccal mucosa microcirculation. This non-invasive approach of measuring oxygen waves as a surrogate parameter of cyclic recruitment and derecruitment could be used to monitor PaO(2) oscillations at the bedside.

Electrical impedance tomography (EIT) is considered useful for monitoring regional ventilation and aeration in intensive-care patients during mechanical ventilation. Changes in their body fluid state modify the electrical properties of lung tissue and may interfere with the EIT measurements of lung aeration. The aim of our study was to assess the effects of crystalloid and colloid infusion and blood withdrawal on bioimpedance determined by EIT in a chest crosssection. Fourteen anaesthetized mechanically ventilated pigs were subjected to interventions affecting the volume state (crystalloid and colloid infusion, blood withdrawal). Six animals received additional crystalloid fluids (fluid group) whereas eight did not (no-fluid group). Global and regional relative impedance changes (RIC, dimensionless unit) were determined by backprojection at endexpiration. Regional ventilation distribution was analyzed by calculating the tidal RIC in the same regions. Colloid infusion led to a significant fall in the global end-expiratory RIC (mean differences: fluid: −91.2, p < 0.001, nofluid: −38.9, p < 0.001), which was partially reversed after blood withdrawal (mean differences, fluid: +45.1, p = 0.047 and no-fluid: +26.2, p = 0.009). The RIC was significantly lower in the animals with additional crystalloids (mean group difference: 45.5, p < 0.001). Global and regional tidal volumes were not significantly affected by the fluid and volume states.

The forced oscillation technique (FOT) allows the measurement of respiratory mechanics in the intensive care setting. The aim of this study was to compare the FOT with a reference method during mechanical ventilation through a tracheal tube. The respiratory impedance spectra were measured by FOT in nine anaesthetized pigs, and resistance and compliance were estimated on the basis of a linear resistance-compliance inertance model. In comparison, resistance and compliance were quantified by the multiple linear regression analysis (LSF) of conventional ventilator waveforms to the equation of motion. The resistance of the sample was found to range from 6 to 21 cmH(2)O s l(-1) and the compliance from 12 to 32 ml cmH(2)O(-1). A Bland-Altman analysis of the resistance resulted in a sufficient agreement (bias -0.4 cmH(2)O s l(-1); standard deviation of differences 1.4 cmH(2)O s l(-1); correlation coefficient 0.93) and test-retest reliability (coefficient of variation of repeated measurements: FOT 2.1%; LSF 1.9%). The compliance, however, was poor in agreement (bias -8 ml cmH(2)O(-1), standard deviation of differences 7 ml cmH(2)O(-1), correlation coefficient 0.74) and repeatability (coefficient of variation: FOT 23%; LSF 1.7%). In conclusion, FOT provides an alternative for monitoring resistance, but not compliance, in tracheally intubated and ventilated subjects.

Background: The pathophysiological concept of acute lung injury (ALI) in combination with ventilator-associated lung injury (VALI) is still unclear. We characterized the histopathological features of intravenous injection of oleic acid (OAI) and lung lavage (LAV) combined with VALI. Methods: Pigs were randomized to the control, LAV or OAI group and ventilated by pressure-controlled ventilation. Measurements included: haemodynamics, spirometry, blood gas analysis, lung wet-to-dry weight ratio (W/D), total protein content in broncho-alveolar lavage fluid (BALF), and lung pathological description and scoring. Results: Five hours after lung injury induction, gas exchange was significantly impaired in both the OAI and the LAV groups. Compared to controls, we found an increase in W/D and histopathological total injury scores in both the LAV and OAI groups and an increase in BALF total protein content in the OAI group. In contrast to the LAV group, the OAI group showed septal necrosis and alveolar oedema. Both groups exhibited dorsal and caudal atelectasis and interstitial oedema. In addition, the OAI group demonstrated a propensity to dorsal necrosis and congestion whereas the LAV group tended to develop ventral overdistension and barotrauma. Conclusions: This study presents a comparison of porcine OAI and LAV models combined with VALI, providing information for study design in research on ALI.

BACKGROUND: In the acute respiratory distress syndrome potentially recruitable lung volume is currently discussed. (3)He-magnetic resonance imaging ((3)He-MRI) offers the possibility to visualize alveolar recruitment directly. METHODS: With the approval of the state animal care committee, unilateral lung damage was induced in seven anesthetized pigs by saline lavage of the right lungs. The left lung served as an intraindividual control (healthy lung). Unilateral lung damage was confirmed by conventional proton MRI and spiral-CT scanning. The total aerated lung volume was determined both at a positive end-expiratory pressure (PEEP) of 0 and 10 mbar from three-dimensionally reconstructed (3)He images, both for healthy and damaged lungs. The fractional increase of aerated volume in damaged and healthy lungs, followed by a PEEP increase from 0 to 10 mbar, was compared. RESULTS: Aerated gas space was visualized with a high spatial resolution in the three-dimensionally reconstructed (3)He-MR images, and aeration defects in the lavaged lung matched the regional distribution of atelectasis in proton MRI. After recruitment and PEEP increase, the aerated volume increased significantly both in healthy lungs from 415 ml [270-445] (median [min-max]) to 481 ml [347-523] and in lavaged lungs from 264 ml [71-424] to 424 ml [129-520]. The fractional increase in lavaged lungs was significantly larger than that in healthy lungs (healthy: 17% [11-38] vs. lavage: 42% [14-90] (P=0.031). CONCLUSION: The (3)He-MRI signal might offer an experimental approach to discriminate atelectatic vs. poor aerated lung areas in a lung damage animal model. Our results confirm the presence of potential recruitable lung volume by either alveolar collapse or alveolar flooding, in accordance with previous reports by computed tomography.

OBJECTIVE: Dynamic ventilation (3)He-MRI is a new method to assess pulmonary gas inflow. As differing airway diameters throughout the ventilatory cycle can influence gas inflow this study intends to investigate the influence of volume and timing of a He gas bolus with respect to the beginning of the tidal volume on inspiratory gas distribution. MATERIALS AND METHODS: An ultrafast 2-dimensional spoiled gradient echo sequence (temporal resolution 100 milliseconds) was used for dynamic ventilation (3)He-MRI of 11 anesthetized and mechanically ventilated pigs. The applied (3)He gas bolus was varied in volume between 100 and 200 mL. A 150-mL bolus was varied in its application time after the beginning of the tidal volume between 0 and 1200 milliseconds. Signal kinetics were evaluated using an in-house developed software after definition of parameters for the quantitative description of (3)He gas inflow. RESULTS: The signal rise time (time interval between signal in the parenchyma reaches 10% and 90% of its maximum) was prolonged with increasing bolus volume. The parameter was shortened with increasing delay of (3)He application after the beginning of the tidal volume. Timing variation as well as volume variation showed no clear interrelation to the signal delay time 10 (time interval between signal in the trachea reaches 50% of its maximum and signal in the parenchyma reaches 10% of its maximum). CONCLUSIONS: Dynamic ventilation (3)He-MRI is able to detect differences in bolus geometry performed by volume variation. Pulmonary gas inflow as investigated by dynamic ventilation (3)He-MRI tends to be accelerated by an increasing application delay of a (3)He gas bolus after the beginning of the tidal volume.

Various supportive and adjunctive therapies to conventional mechanical ventilation have been evaluated in patients with acute lung injury and acute respiratory distress syndrome (e.g. nitric oxide, prone position, surfactant, glucocorticoids). Although some investigations have shown promising improvements in oxygenation and physiological variables, large randomized trials of adjunctive and supportive therapies showed no impact on survival.

Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia.HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression.In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways.Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia exposure may produce rapid and substantial damage to the human heart.

Background: PGD following LuTX carries significant morbidity and mortality. AP301, an activator of ENaC-mediated Na(+) uptake represents a new concept for treatment of hyper-permeability oedema with promising preclinical results. Aims: This study aims to investigate the effect of AP301 on patients with PGD≥1 at ICU arrival after LuTX. Methods: Prospective randomised, placebo-controlled pilot-study. All patients fulfilling inclusion criteria are screened for PGD at ICU arrival. After randomization AP301 or placebo is administered via nebulizer twice daily for 7 days or until extubation. Otherwise patients are treated according to clinical routine protocol and followed for 30 days within the study. Results: From 7/2013-8/2014 20 patients were randomised 1:1 to AP301 (group 1) or placebo (group 2). Demographics were comparable in both groups as well as mean PaO2/FiO2 ratio at time of inclusion (236±91 vs 214±96). Patients in group 1 had a significantly shorter duration of intubation with 2±0,8 vs 3,7±2 days (p=0,02). There was a trend towards a shorter ICU stay (7,5±3,1 vs 10,8±8,7 days) and increased PaO2/FiO2 ratio in group 1 at 24h (313±126 vs 240±90), 48h (486±59 vs 460±33), 72h (504±40 vs 427±78) and 96h postoperative (549±0 vs 370±96). Thereafter no patient in group 1 was ventilated. 30-day survival was 100%. Conclusion: This pilot study showed impressive clinical effects of AP301 on patients with PGD after primary LuTX leading to a significantly shorter intubation time and a trend towards improved gas exchange and shorter ICU stay. Further investigation of AP301 for PGD treatment is warranted.

BACKGROUND Little is known about real-time in-vivo microscopy of pulmonary capillary perfusion because current microscopy requires direct access to lung tissue with surgical intervention such as the thoracic-window technique and open-lung model. OBJECTIVES To evaluate if probe-based confocal laser scanning endomicroscopy (pCLE) via the trachea allows for real-time in-vivo visualisation of pulmonary capillary density and red blood cell (RBC) velocity in pigs. DESIGN An interventional animal study. SETTING European University Hospital. ANIMALS Nine female domestic pigs (50 to 60 kg) were used. MAIN OUTCOME MEASURES A pCLE probe was positioned in non-dependent, central and dependent lung zones in nine anaesthetised pigs (Alveoflex, Cellvizio, Maunakea, France). After intravenous administration of fluorescein isothiocyanate dextran as contrast agent repetitive pCLE videos were recorded during pressure-controlled ventilation (PCV) or continuous positive airway pressure for 3 min each. Using fluorescein isothiocyanate-labelled RBC erythrocyte velocities in pulmonary capillaries were quantified. Data are expressed as mean ± SD or median with interquartile range (IQR). RESULTS Capillary density was greater in dependent and central as compared with non-dependent lung zones [[32 (29 to 34) %] and 32 (30 to 34) % vs. 28 (26 to 28) %, respectively, P 20 μm, 309 μm s(-1) (209 to 397)] than intermediate [diameter 10.1 to 20 μm, 146 μm s(-1) (118 to 235)] and small [diameter

OBJECTIVE Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN Prospective randomized study. SETTING Laboratory investigation. SUBJECTS Piglets, average weight 30 ± 2 kg. INTERVENTIONS At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

BACKGROUND: Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. METHODS: In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. RESULTS: CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P

In a surfactant-depletion model of lung injury, tidal recruitment of atelectasis and changes in shunt fraction lead to large Pao2 oscillations. We investigated the effect of these oscillations on conventional arterial blood gas (ABG) results using different sampling techniques in ventilated rabbits. In each rabbit, 5 different ventilator settings were studied, 2 before saline lavage injury and 3 after lavage injury. Ventilator settings were altered according to 5 different goals for the amplitude and mean value of brachiocephalic Pao2 oscillations, as guided by a fast responding intraarterial probe. ABG collection was timed to obtain the sample at the peak or trough of the Pao2 oscillations, or over several respiratory cycles. Before lung injury, oscillations were small and sample timing did not influence Pao2. After saline lavage, when Po2 fluctuations measured by the indwelling arterial Po2 probe confirmed tidal recruitment, Pao2 by ABG was significantly higher at peak (295 +/- 130 mm Hg) compared with trough (74 +/- 15 mm Hg) or mean (125 +/- 75 mm Hg). In early, mild lung injury after saline lavage, Pao2 can vary markedly during the respiratory cycle. When atelectasis is recruited with each breath, interpretation of changes in shunt fraction, based on conventional ABG analysis, should account for potentially large respiratory variations in arterial Po2.

Minimal scan times in rapid fluorine-19 MRI using sulfur hexafluoride (SF6) have been on the order of 10 s. Because of the very short T1 relaxation time of SF6 (T1 = 1.65 ms), high receiver bandwidths are necessary to allow for a high number of excitations. Since high bandwidths cause high levels of electronic noise, SNR per acquisition has been too low to further reduce scan time. The purpose of this study was to investigate whether scan times could be reduced using hexafluoroethane (C2F6), a gas with a longer T1 (T1 = 7.9 ms) at a relatively low bandwidth of 488 Hz/pixel. Gradient-echo images were acquired during and after completion of the wash-in of a 70% C2F6- 30% O2 mixture. Peak SNR values of 16 and 7.9 were observed for coronal projection images acquired within 2 s and 260 ms, respectively. These results demonstrate that subsecond imaging is feasible using C2F6.

Rasche Anderungen der Lungenbeluftung und -durchblutung, wie zum Beispiel beim Rekrutieren von Atelektasen im Acute Respiratory Distress Syndrome (ARDS) oder wahrend der kardiopulmonalen Reanimation, lassen starke Schwankungen des Sauerstoffpartialdrucks (pO2) im arteriellen Blut erwarten. Ein schneller pO2-Messsensor (Foxy-AL 300™) mit einer zeitlichen Auflosung von bis zu 80 ms ermoglicht eine Online-Messung dieser pO2-Schwankungen und stellt im Tierexperimenten erstmals in Aussicht, diese Veranderungen unmittelbar zu quantifizieren und therapeutischen Interventionen zuzuordnen.

Der Transport von pulmonal kritischen Patienten stellt logistisch und personell hohe Anforderungen. Eine luckenlose Uberwachung der Vitalparameter ist obligat. Die Herz-Kreislauf-Funktionen konnen kontinuierlich uberwacht werden (EKG, invasive Blutdruckmessung). Fur die Uberwachung einer Beatmungstherapie wahrend Transporten in Hubschraubern oder bodengebundenen Rettungsmitteln stehen die Pulsoxymetrie, Kapnometrie und ggf. Atemwegsfluss- und -druckmessung zur Verfugung. Aufgrund der lauten Umgebung ist die Auskultation der Atemgerausche z. B. zur Verifizierung der Tubuslage nicht geeignet. Ein neues, bisher nur experimentell eingefuhrtes funktionelles bildgebendes Verfahren, die elektrische Impedanztomographie (EIT), kann Veranderungen der Lungenbeluftung detektieren. Die EIT erfasst Impedanzanderungen in der Lunge, die durch den unterschiedlichen Luftgehalt in Inspiration und Exspiration entstehen. Diese Impedanzanderungen werden in einer 2-dimensionalen Matrix generiert und stellen so die Ventilation der Lunge atemzugweise dar. Veranderungen der aktuellen Beatmungseinstellungen und deren Auswirkung auf die Lungenbeluftung konnen quantifiziert werden. Die EIT ist ein nichtinvasives, fur den Patienten ungefahrliches Verfahren zur Verlaufskontrolle einer invasiven Beatmungstherapie. Sie konnte in Zukunft bei Verlegungen und Transporten beatmeter Patienten als bildgebendes Verfahren genutzt werden und so einen weiteren Beitrag zur Patientensicherheit liefern.

Ziel: Dynamische CT-Untersuchungen (dCT) erlauben die Darstellung und Quantifizierung ventilierter Lungenflache und Atelektasenbildung wahrend kontinuierlicher Beatmung. Diese Studie ­vergleicht eine quantitative Auswertung einer infrakarinalen dCT-Einzelschicht mit der einer Spiral-CT der gesamten Lunge, um zu untersuchen, ob eine dynamisch gemessene Einzelschicht bezuglich der intrapulmonalen Atelektasenverteilung reprasentativ fur die Gesamtlunge ist. Material und Methoden: An 8 gesunden Schweinen erfolgte eine dCT (Schichtdicke 1 mm, zeitliches Inkrement 100 ms) wahrend kontinuierlicher Beatmung, gefolgt von einer Spiral-CT der gesamten Lunge (Schichtdicke 2 mm; Pitch 1,5; Inkrement 2 mm) wahrend inspiratorischen Atemanhalts (Atemwegsdruck 20 mbar). Nach Segmentierung und Dichteplanimetrie der Datensatze mittels einer dafur entwickelten Auswertesoftware wurde eine Differenzierung des Lungengewebes in folgende funktionelle Lungenkompartimente vorgenommen: uberblahte Lunge (- 1024 bis - 910 HE); normoventiliert (- 910 bis - 300 HE); Atelektasen (- 300 bis + 200 HE). Ergebnisse: Die gemittelten Anteile der Dichtebereiche in den dCT-Serien korrelierten mit der Dichteanalyse der Spiral-CT wie folgt: uberblahte Lungenanteile r = 0,56; normoventiliert r = 0,83; Atelektasen r = 0,84. Die Spiral-CT-Auswertung zeigte folgende prozentuale Aufteilung der Lungenkompartimente: uberblaht 3,1 %; normoventiliert 77,9 %; Atelektasen 19,0 %. Die dCT ergab folgende Verteilung der Gesamtlungenflache: uberblahte Lungenflache 6,4 %; normoventiliert 65,2 %; Atelektasen 28,4 %. Schlussfolgerungen: Die Ergebnisse dieser Studie lassen schlussfolgern, dass die Auswirkungen unterschiedlicher Beatmungsstrategien auf die Atelektasenbildung mittels dCT erfasst werden konnen. Hierbei ist jedoch zu beachten, dass es aufgrund eines kraniokaudalen Gradienten der Atelektasenverteilung zu einer systematischen Abweichung zwischen dCT und Spiral-CT kommt. Die uberblahten und atelektatischen Lungenanteile werden in der infrakarinalen Untersuchungsschicht mittels dCT uberschatzt, die normoventilierten Areale unterschatzt. Purpose: Dynamic CT (dCT) allows visualization and quantification of ventilated lung and atelectases with high temporal resolution during continuous ventilation. This study compares a quantitative image analysis in a subcarinal single slice dCT series versus a whole lung spiral-CT, in order to analyze, whether the distribution of atelectasis of a single dCT series is representative for the whole lung. Materials and Methods: dCT in sliding windows technique (slice thickness 1 mm, temporal increment 100 ms) was performed in 8 healthy pigs 3 cm caudal to the ca­rina during continuous mechanical ventilation. Subsequently, a spiral-CT of the whole lung (slice thickness 2 mm; pitch 1.5; increment 2 mm) was acquired during inspiratory breath hold (airway pressure 20 mbar). Lung segmentation and planimetry of predefined density ranges were achieved using a dedicated software tool in both data-sets. Thus, the fractions of the following functional lung compartments were averaged over time: hyperinflated lung (- 1024 to - 910 HE), normal ventilated lung - 900 to - 300 HE) and atelectasis (- 300 to + 200 HE). Results: Quantitative analysis of dCT-series during continuous respiration correlated with the density analysis in spiral-CT as follows: hyperinflated lung r = 0.56; normal ventilated lung r = 0.83 and atelectases r = 0.84. Analysis of spiral-CT showed the following distribution of functional lung compartments: hyperinflated lung 3.1 % normal ventilated lung 77.9 % and atelectasis 19.0 %. In dCT, hyperinflated lung represented 6.4 %, normal ventilated lung 65.2 % and atelectasis 28.4 % of total the lung area. Conclusion: The results of our study demonstrate that dCT allows monitoring of atelectasis formation in response to different ventilatory strat­egies. However, a deviation between dCT and spiral-CT has to be taken into account. In subcarinal dCT series, hyperinflated lung areas and atelectases were overestimated due to a craniocaudal gradient of atelectases, whereas normal ventilated lung was underestimated.

Background Fast dynamic computed tomography (dCT) has been used to assess regional dynamics of lung inflation and deflation processes. The aim of this study was to relate ventilation-induced changes in lung density distribution, as measured over several respiratory cycles by dCT, to oxygenation and shunt fraction in a lavage acute respiratory distress syndrome model. Methods Six anaesthetized pigs underwent pressure-constant ventilation (F I O2=1.0, inspiratory:expiratory ratio=1:1) before and after induction of lung damage by saline lavage. Mean airway pressure ( P a μ w μ ) was varied (8, 13, 18, 23, 28, 33, and 38 cm H2O) in random order. At each P a μ w μ level, dCT acquisitions were performed over several respiratory cycles (Somatom Plus4, Siemens; supradiaphragmatic transverse slice; thickness=1 mm; temporal resolution=100 ms). During scanning at each P a μ w μ , arterial and mixed venous blood were obtained for blood gas analysis and shunt calculation. In each CT image, fractional areas (FA) of defined density ranges representing ventilated lung and atelectasis were determined by planimetry using dedicated software. The FA data of individual 100 ms scans were averaged over several respiratory cycles, and expressed as mean FA in percentage of total lung area at each P a μ w μ . For atelectatic lung parenchyma a quantitative relationship of the respective mean FA to shunt fraction was studied using regression analysis. Results Under steady-state conditions, mean FA of atelectasis correlated linearly with the calculated shunt fraction (healthy lungs, r=+0.76; lavaged lungs, r=+0.89). There is a non-linear relationship between mean FA of ventilated lung parenchyma and mean FA of atelectasis with PaO2. Conclusions We conclude that dCT allows assessment of the effects of ventilator adjustments and resultant P a μ w μ ; changes upon lung aeration and oxygenation rapidly, and with good spatial and temporal resolution. This may benefit patients with acute lung injury, whose ventilatory pattern may be optimized as early as during their first diagnostic workup.

This study examined whether ARDS patients in whom predefined ventilator settings fail to maintain oxygenation and CO2 removal can be safely transitioned to high-frequency oscillatory ventilation (HFOV), and whether HFOV use is efficacious.Prospective observational study in the 14-bed intensive care unit of a university hospital.42 patients with ARDS (APACHE II score 28 (IQR 24-37) and ventilation time prior HFOV 3.0 days (0.7-9.1).Gas exchange parameters and ventilator data were recorded before and during HFOV treatment (-12 h, -6 h, baseline, 10 min, 1 h, 6 h, 12 h, 24 h). Primary endpoints included: (a) PaO2/FIO2 ratio 24 h after start of HFOV treatment or the last point of measurement if HFOV ended within the first 24 h; (b) HFOV-related complications. Post hoc analysis assessed the relationship between outcome and the response to HFOV, and between outcome and time of mechanical ventilation prior to HFOV. At baseline the median PaO2/FIO2 ratio was 95 (IQR 62-129); after 24 h of HFOV the PaO2/FIO2 ratio had increased significantly to 165 (88-225); only one patient developed a unilateral pneumothorax. Of the 42 patients 18 (43%) had died by day 30. Subset analyses showed a significantly higher 30-day mortality rate in patients with at least 3 days of mechanical ventilation prior to HFOV (64%) and in patients without oxygenation improvement after 24 h on HFOV (71%).HFOV is an effective and safe method to ventilate ARDS patients. Failure to improve oxygenation within 24 h of HFOV is associated with high mortality.

Background: To use 3Helium (3He)-MRI in patients with unilateral lung grafts to assess the contributions of graft and native lung to total ventilated lung volume, and second to compare conventional measurements of intrapulmonary gas volume (spirometry, body plethysmography) with image-based volumetry of ventilated lung parenchyma visualized by hyperpolarized 3He-MRI. Methods: With Ethics Committee approval, five patients with single lung transplantation (SLTX) for idiopathic pulmonary fibrosis (IPF) underwent both conventional pulmonary function testing (PFT) and 3He-MRI of the lung. Intrapulmonary gas volume (GV) during the inspiratory breathhold for 3He-MRI was calculated from measured functional residual capacity (corrected for supine position) and inspired tidal volume. Image-based global and regional lung volumetries (LV) were performed in three-dimensionally reconstructed 3He-MR images (corrected for the fraction of tissue and blood). Results: Transplanted lungs were characterized by a homogeneous distribution of signal intensity, whereas the native lungs of the patients suffering from IPF displayed an inhomogeneous signal distribution pattern with numerous round or wedge-shaped ventilation defects. Total ventilated lung volume determined by 3He-MRI correlated well with PFT-based measurements, but with a systematic overestimation of the 3He-based lung volumetry of approximately 20%. Functioning lung grafts contributed 66±6% and their corresponding native IPF lungs 34±6% to total ventilated volume (P

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 μg/kg), followed by a continuous infusion (13 μg/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.

The inhaled route is a promising new way for administering drugs to the human body. Flow and particle deposition in the human respiratory tract depends on the individual's anatomy as well as on the drug composition. A European Framework V Program supported project is currently developing a simulation tool for assessment of drug distribution and deposition. This tool relies heavily on the input of radiological data sets, which are obtained in humans. Both high temporal and spatial resolutions are required, and CT and MRI (including hyperpolarized helium-3 MRI) are applied. The radiological data are integrated into computation fluid dynamics software, which is capable of assessing air-flow profiles and compartmental behaviours. This is complemented by pharmacokinetic models, which should result in a simulation tool that will be of use for the theoretical design of new inhaled therapies. This article describes the special imaging requirements of each region of the respiratory tract and the feasibility of these sophisticated radiological techniques with a view of using these data in a simulation model of the lung.

PURPOSE Determination of the intrahepatic distribution volume of two contrast media (CM) by CT-guided application in an ex-vivo and an in-vivo model (pig liver). MATERIAL AND METHODS In pig livers ex-vivo and in-vivo, 131 CT-guided injections of two different CM (Imagopaque(R), Visipaque(R)) were performed using catheters and cannula with and without side-holes and documented by spiral CT. The distribution pattern was assessed visually: interstitial, subcapsular, vascular/tubular, the distribution volume was quantified using a density mask (thresholds 70/400 HE). RESULTS Purely interstitial applications were achieved more frequently in-vivo than ex-vivo (p = 0.001). There were no relevant differences between the two CM. Catheters without side-holes led to more interstitial CM depots than catheters with side-holes (p = 0.005). The mean distribution volume was larger with catheters with side-holes (ex-vivo 103 cm(3), in-vivo 19 cm(3)) than with catheters without side-holes (ex-vivo 67 cm(3), in-vivo 13 cm(3)) (p = 0,01). At the same time, the mean density with catheters with side-holes (102 HE) was lower than with catheters without side-holes (115 HE) (p = 0.005). CONCLUSION Marked differences of the CM distribution volumes were observed between ex-vivo and in-vivo studies in the pig model. Catheters with side-holes are far superior to catheters without.

Computed tomography (CT) is the method of choice for the morphological assessment of pulmonary structure. Airways. pulmonary parenchyma and their pathologies are shown with high spatial resolution. Airway diseases exhibit bronchial dilatation, wall thickening and an increased visibility in the lung periphery. CT is also the imaging gold standard for the detection and the characterisation of emphysema because a high degree of concordance with histopathological studies. Centrilobular, panlobular and paraseptal emphysema can be differentiated. CT can also provide functional information. Paired inspiratory and expiratory scans with or without spirometric triggering allow to evaluate obstruction of the small airways (airtrapping). On the basis of CT-data lung volumes can be semented. Cine-CT allows to visualise motion of the central airways. e.g. in tracheomalacia, to assess regional ventilation to calculate pulmonary time constants. and to display the co-ordinated or dissociated motion of the thoracic wall and the diaphragm. Beyond the mere high-resolution visualisation of the structure of the lung the application of these CT-strategies makes a regional assessment of pulmonary function possible.

Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO₂ recordings (direct hint). SpO₂ oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint).Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI.Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hours after induction of lung injury (mean calculated amplitude: 57.1 mmHg reflecting shunt oscillations of 8.4% in mean). The SHAM group had no relevant oxygen oscillations (30 mmHg, shunt oscillations1.5%). Synchronously to oxygen oscillations, EIT depicted (1) a decrease of ventilation in dorsal areas, (2) an increase in ventral areas, (3) a decrease of especially dependent expiratory impedance, 3) an increase in late inspiratory flow especially in the dependant areas, (4) an increase in the speed of peak expiratory flow (PEF), and (5) a decrease of dorsal late expiratory flow.SpO2 and EIT recordings detect events that are interpreted as cyclical recruitment of atelectasis.

Highlights • Real time detection of cyclical atelectasis is fundamental for individualised mechanical-ventilation therapy in ARDS. • Intra-arterial oxygen sensors could be used to detect the breath-by-breath oscillations in PO2 during cyclical atelectasis. • The fidelity with which oxygen sensors can detect these arterial PO2 oscillations depends on the sensors’ speed of response. • We present a system for testing fast-response fibre optic oxygen sensors under simulated conditions of cyclical atelectasis. • We show that a prototype fibre optic oxygen sensor, compatible with clinical use, can detect rapid PO2 changes in vitro., Two challenges in the management of Acute Respiratory Distress Syndrome are the difficulty in diagnosing cyclical atelectasis, and in individualising mechanical ventilation therapy in real-time. Commercial optical oxygen sensors can detect PaO2 oscillations associated with cyclical atelectasis, but are not accurate at saturation levels below 90%, and contain a toxic fluorophore. We present a computer-controlled test rig, together with an in-house constructed ultra-rapid sensor to test the limitations of these sensors when exposed to rapidly changing PO2 in blood in vitro. We tested the sensors’ responses to simulated respiratory rates between 10 and 60 breaths per minute. Our sensor was able to detect the whole amplitude of the imposed PO2 oscillations, even at the highest respiratory rate. We also examined our sensor's resistance to clot formation by continuous in vivo deployment in non-heparinised flowing animal blood for 24 h, after which no adsorption of organic material on the sensor's surface was detectable by scanning electron microscopy.

BACKGROUND: Vibration response imaging (VRI) is a bedside technology to monitor ventilation by detecting lung sound vibrations. It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs. We therefore compared VRI to electrical impedance tomography (EIT), an established technique used for the assessment of regional ventilation. METHODOLOGY/PRINCIPAL FINDINGS: Simultaneous EIT and VRI measurements were performed in the healthy and injured lungs (ALI; induced by saline lavage) at different PEEP levels (0, 5, 10, 15 mbar) in nine piglets. Vibration energy amplitude (VEA) by VRI, and amplitudes of relative impedance changes (rel.ΔZ) by EIT, were evaluated in seven regions of interest (ROIs). To assess the distribution of tidal volume (VT) by VRI and EIT, absolute values were normalized to the VT obtained by simultaneous spirometry measurements. Redistribution of ventilation by ALI and PEEP was detected by VRI and EIT. The linear correlation between pooled VT by VEA and rel.ΔZ was R(2) = 0.96. Bland-Altman analysis showed a bias of -1.07±24.71 ml and limits of agreement of -49.05 to +47.36 ml. Within the different ROIs, correlations of VT-distribution by EIT and VRI ranged between R(2) values of 0.29 and 0.96. ALI and PEEP did not alter the agreement of VT between VRI and EIT. CONCLUSIONS/SIGNIFICANCE: Measurements of regional ventilation distribution by VRI are comparable to those obtained by EIT.

Purpose of the Study: Detection of cyclical recruitment of atelectasis after induction of lavage (LAV) or oleic acid injury (OAI) in mechanically ventilated pigs. Primary hypothesis is that oxygen oscillations within the respiratory cycle can be detected by SpO2 recordings (direct hint). SpO2 oscillations reflect shunt oscillations that can only be explained by cyclical recruitment of atelectasis. Secondary hypothesis is that electrical impedance tomography (EIT) depicts specific regional changes of lung aeration and of pulmonary mechanical properties (indirect hint). Materials and Methods: Three groups (each n = 7) of mechanically ventilated pigs were investigated applying above mentioned methods before and repeatedly after induction of lung injury: (1) sham treated animals (SHAM), (2) LAV, and (3) OAI. Results: Early oxygen oscillations occurred in the LAV group (mean calculated amplitude: 73.8 mmHg reflecting shunt oscillation of 11.2% in mean). In the OAI group oxygen oscillations occurred hou...

A method for in vivo measurement of oxygen partial pressure (pO2) in porcine lungs during partial liquid ventilation (PLV) with perflubron (PFOB) was developed. A pulse sequence for high-resolution MRI of the distribution of PFOB in the lung after intratracheal administration was developed as well. Moreover, quantitative measurements of longitudinal relaxation time T(1) of (19)F resonances for assessment of regional pO2 are described. Due to the need to acquire data during a single expiratory breathhold, only low SNRs were achieved in vivo. Therefore, simulations were performed to investigate the influence of background noise on T(1) values calculated from data with low SNR. Based on these simulations, a postprocessing strategy was developed to correct for systematic errors by background noise prior to quantitative analysis. Results of a pilot study in pigs under conditions of PLV are presented.

Purpose: Density measurements in dynamic CT image series of the lungs allow one to quantify ventilated, hyperinflated, and atelectatic pulmonary compartments with high temporal resolution. Fast automatic segmentation of lung parenchyma and a subsequent evaluation of it's respective density values are a prerequisite for any clinical application of this technique. Material and Methods: For automatic lung segmentation in thoracic CT scans, an algorithm was developed which uses (a) different density masks, and (b) anatomic knowledge to differentiate heart, diaphragm and chest wall from ventilated and atelectatic lung parenchyma. With Animal Care Committee approval, the automated technique was tested in 8 anaesthetized ventilated pigs undergoing dynamic CT before and after induction of lavage-ARDS. Images were acquired in one supradiaphragmatic, cross-sectional slice (temporal resolution of 100 ms; slice thickness of 1 mm, high resolution reconstruction algorithm). In 120 CT images the total pixel number and the calculated MLD from the automatically segmentated lung were compared to the values obtained from an interactive lung segmentation. Results: The software tool was able to read all image series (DICOM standard). Automatic and interactive segmentation were in high agreement (R 2 =0.99 for the total number of pixels and the MLD). Originally, the most frequent error was misclassification of atelectasis as extrapulmonary solid tissue. Conclusion: An automatic software tool is presented for lung segmentation in healthy lungs and in ARDS. Aerated lung and atelectasis were identified with high accuracy. This post-processing tool allows for a quantitative, CT based assessment of ventilation and recruitment processes in the lung. Thus, it may help to optimize ventilation patterns in patients with ARDS.

A new method for dynamic imaging of pulmonary wash-in and wash-out kinetics of inhaled sulfur hexafluoride (SF6) gas was developed. Measurements at the fluorine-19 Larmor frequency were performed in pigs using a gradient echo pulse sequence with 0.5 ms echo time and a measurement time of 9.1 s per image. Dynamic MRI was performed during wash-in and wash-out of SF6 gas in mechanically ventilated porcine lungs. A postprocessing strategy was developed for quantitative determination of wash-out time constants in the presence of noise. Mean wash-out constants were 4.78 ± 0.48 breaths vs. 4.33 ± 0.76 breaths for left and right lung when ventilation was performed with low tidal volume, and 1.73 ± 0.16 breaths vs. 1.85 ± 0.11 breaths with high tidal volume ventilation. In conclusion, breath-hold MRI of SF6 gas is feasible in large animals. Moreover, regional wash-in and wash-out kinetics of SF6 can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605–613, 2001. © 2001 Wiley-Liss, Inc.

Purpose 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.

To develop a validated post-processing routine for volumetry of the ventilated airspaces by 3He MRI.3Helium MRI and pulmonary function tests were performed in seven healthy volunteers. After segmentation of ventilated airspaces, their volumes were calculated. Functional residual capacity (FRC) was used as a reference. For comparison of absolute volumes, correction factors were evaluated.Mean lung volume (+/- standard deviation) calculated from 3He MRI was 4,082 +/- 908 mL and mean FRC was 3,696 +/- 1166 mL, with a mean difference of 386 mL (r = 0.88). After correction for the relative pulmonary air content (factor 0.82), posture (0.72), and the individual tidal volume, 3He MRI volume was 3,348 +/- 744 mL and mean FRC was 3,422 +/- 817 mL, with the mean difference down to -74 mL (r = 0.9). Comparison on an individual basis confirmed an improvement in the estimation of absolute lung volume.Volumetry of ventilated lung from 3He MRI shows high correlation and good agreement with the results of pulmonary function tests.

Background Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B). Methods Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring. Results The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring. Conclusions In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.

Breathhold 19 F-Magnetic Resonance Imaging of Lung Ventilation using SF 6 Gas. Objective: Development of a method to analyze lung ventilation by 19 F-magnetic resonance imaging (MRI) of inspired SF 6 gas during breathhold. Material and Methods: Measurements were performed with a Siemens Magnetom Vision 1.5T scanner using the conventional gradient overdrive. Coronal images of the lung were acquired using ultrafast gradient-echo pulse sequences with TR/TE/α = 1.4 ms/ 0.48 ms/40° without slice selection. With NEX = 200 averages and MA = 32 × 64 raw data matrix, the acquisition time was 9s/image. Higher spatial resolution of 4.7 × 6.3 × 15 mm 3 was obtained with a three-dimensional pulse sequence (TR/TE/ α = 1.6 ms/0.48 ms/65°, NEX = 20) running for 49 s. Measurements wer performed in three anesthetized and ventilated pigs (18 kg). Results: A nearly linear relation between SF 6 concentration and 19 F signal intensity was observed. The signal-to-noise ratio in images obtained without slice selection was 30.9, with slice selection it was 14.9. No differences between SF 6 distribution to both lungs were observed in the animals. Conclusion: Breathhold MRI of SF 6 gas distribution in the lung was demonstrated for the first time. The low spin-density was compensated for by highly repetitive signal averaging. Breathhold 19 F-MR imaging of ventilated airspaces to assess SF 6 distribution in the human lung appears to be an interesting new method, which can be implemented with little technical efforts, and does not rely on radioactive isotopes.

Objective Assessment of the temporal and spatial dynamics of hyperpolarized Helium-3 (3He) distribution in the lung with ultrafast gradient-echo magnetic-resonance imaging. Material and methods Coronal images of the lung were acquired using ultrafast gradient-echo pulse sequences with TR/TE = 3.3 ms/1.3 ms (slice thickness, 40 mm) and TR/TE = 2.0 ms/0.7 ms (without slice selection). A series of 80 or 160 projection images was obtained with 210 ms or 130 ms temporal resolution, respectively. Imaging was performed during several respiratory cycles after application of a single bolus of 300 mL hyperpolarized 3He. Measurements were performed in six healthy volunteers (spontaneous breathing). Results Different phases of in- and expiration could be visualized. During the course of consecutive respiratory cycles the 3He signal decreased due to dilution of 3He in residual alveolar gas and by inspired air, relaxation due to oxygen and the RF pulses, and due to Helium-3 washout. The signal of a single bolus of 3He was detected in the lung for up to four respiratory cycles. Anatomical structures were better visualized on slice selective images than on images without slice selection. Conclusion Distribution of inspired 3He within the tracheobronchial tree and alveolar space and its washout can be visualized by ultrafast imaging of a single bolus of hyperpolarized 3He gas. This method may allow for regional analysis of lung function with temporal and spatial resolution superior to conventional methods.

We applied a recently developed method of following the time course of the intrapulmonary oxygen partial pressure p(O2)(t) during apnea by (3)He MRI to healthy volunteers. Using two imaging series with different interscan times during two breathholds (double acquisition technique), relaxation of (3)He due to paramagnetic oxygen and depolarization by RF pulses were discriminated. In all four subjects, the temporal evolution of p(O2) was found to be linear, and was described by an initial partial pressure p(0) and a decrease rate R. Also, regional differences of both p(0) and R were observed. A correlation between p(0) and R was apparent. Finally, we discuss limitations of the double acquisition approach.

Inhalation of hyperpolarized 3He allows magnetic resonance imaging (MRI) of ventilated airspaces.3He hyperpolarization decays more rapidly when interacting with paramagnetic O2. We describe a method for in vivo determination of intrapulmonary O2 concentrations ([O2]) based on MRI analysis of the fate of measured amounts of inhaled hyperpolarized3He in imaged regions of the lung. Anesthetized pigs underwent controlled normoventilation in a 1.5-T MRI unit. The inspired O2 fraction was varied to achieve different end-tidal [O2] fractions ([Formula: see text]). With the use of a specifically designed applicator,3He (100 ml, 35–45% polarized) was administered at a predefined time within single tidal volumes. During subsequent inspiratory apnea, serial two-dimensional images of airways and lungs were acquired. At least once in each animal studied, the radio-frequency excitation used for imaging was doubled at constant[Formula: see text]. Signal intensity measurements in regions of interest of the animals' lungs (volume range, 54–294 cm3), taken at two different radio-frequency excitations, permitted calculation of [O2] in these regions of interest. The [O2] fractions in the regions of interest correlated closely with[Formula: see text]( R = 0.879; P < 0.0001). O2-sensitive3He-MRI may allow noninvasive study of regional distribution of ventilation and alveolar[Formula: see text] in the lung.

We present a new method to determine in vivo the temporal evolution of intrapulmonary oxygen concentrations by functional lung imaging with hyperpolarized (3)Helium ((3)He-->). Single-breath, single-bolus visualization of (3)He--> administered to the airspaces is used to analyze nuclear spin relaxation caused by the local oxygen partial pressure p(O(2))(t). We model the dynamics of hyperpolarization in the lung by rate equations. Based hereupon, a double acquisition technique is presented to separate depolarization by RF pulses and oxygen induced relaxation. It permits the determination of p(O(2)) with a high accuracy of up to 3% with simultaneous flip angle calibration using no additional input parameters. The time course of p(O(2)) during short periods of breathholding is found to be linear in a pig as well as in a human volunteer. We also measured the wall relaxation time in the lung and deduced a lower limit of 4.3 min.

Varying pulmonary shunt fractions during the respiratory cycle cause oxygen oscillations during mechanical ventilation. In artificially damaged lungs, cyclical recruitment of atelectasis is responsible for varying shunt according to published evidence. We introduce a complimentary hypothesis that cyclically varying shunt in healthy lungs is caused by cyclical redistribution of pulmonary perfusion. Administration of crystalloid or colloid infusions would decrease oxygen oscillations if our hypothesis was right. Therefore, n=14 mechanically ventilated healthy pigs were investigated in 2 groups: crystalloid (fluid) versus no-fluid administration. Additional volume interventions (colloid infusion, blood withdrawal) were carried out in each pig. Intra-aortal PaO2 oscillations were recorded using fluorescence quenching technique. Phase shift of oxygen oscillations during altered inspiratory to expiratory (I:E) ventilation ratio and electrical impedance tomography (EIT) served as control methods to exclude that recruitment of atelectasis is responsible for oxygen oscillations. In hypovolemia relevant oxygen oscillations could be recorded. Fluid and volume state changed PaO2 oscillations according to our hypothesis. Fluid administration led to a mean decline of 105.3 mmHg of the PaO2 oscillations amplitude (P0.001). The difference of the amplitudes between colloid administration and blood withdrawal was 62.4 mmHg in pigs not having received fluids (P=0.0059). Fluid and volume state also changed the oscillation phase during altered I:E ratio. EIT excluded changes of regional ventilation (i.e., recruitment of atelectasis) to be responsible for these oscillations. In healthy pigs, cyclical redistribution of pulmonary perfusion can explain the size of respiratory-dependent PaO2 oscillations.

Background In pressure support ventilation (PSV), a non-variable level of pressure support is delivered by the ventilator when triggered by the patient. In contrast, variable PSV delivers a level of pressure support that varies in a random fashion, introducing more physiological variability to the respiratory pattern. Experimental studies show that variable PSV improves gas exchange, reduces lung inflammation and the mean pressure support, compared to non-variable PSV. Thus, it can theoretically shorten weaning from the mechanical ventilator. Methods/design The ViPS (variable pressure support) trial is an international investigator-initiated multicenter randomized controlled open trial comparing variable vs. non-variable PSV. Adult patients on controlled mechanical ventilation for more than 24 hours who are ready to be weaned are eligible for the study. The randomization sequence is blocked per center and performed using a web-based platform. Patients are randomly assigned to one of the two groups: variable PSV or non-variable PSV. In non-variable PSV, breath-by-breath pressure support is kept constant and targeted to achieve a tidal volume of 6 to 8 ml/kg. In variable PSV, the mean pressure support level over a specific time period is targeted at the same mean tidal volume as non-variable PSV, but individual levels vary randomly breath-by-breath. The primary endpoint of the trial is the time to successful weaning, defined as the time from randomization to successful extubation. Discussion ViPS is the first randomized controlled trial investigating whether variable, compared to non-variable PSV, shortens the duration of weaning from mechanical ventilation in a mixed population of critically ill patients. This trial aims to determine the role of variable PSV in the intensive care unit. Trial registration clinicaltrials.gov NCT01769053

All calls and all feedback interviews were recorded, transcribed and analyzed thematically, using a phenomenological approach to the data. Results: In all incidents (n=33) the laypeople, agreed to participate in a feedback interview. The following themes were identified as important to the bystanders: the challenge of identifying OHCA, the collaboration with the medical dispatcher and the ambulance crew, coping with the experience of sudden death, reflections on whatmore could have been done and experience for the future, the outcome of the patient and the perceptual experience with OHCA. Conclusions: The results from the first 33 cases indicate a need for feedback for laypeople and have identified specific themes important to the laypersons, which need to be explored further.