TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants

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

Detection of inspiratory recruitment of atelectasis by automated lung sound analysis as compared to four-dimensional computed tomography in a porcine lung injury model

Background: Cyclic recruitment and de-recruitment of atelectasis (c-R/D) is a contributor to ventilator-induced lung injury (VILI). Bedside detection of this dynamic process could improve ventilator management. This study investigated the potential of automated lung sound analysis to detect c-R/D as compared to four-dimensional computed tomography (4DCT). Methods: In ten piglets (25 ± 2 kg), acoustic measurements from 34 thoracic piezoelectric sensors (Meditron ASA, Norway) were performed, time synchronized to 4DCT scans, at positive end-expiratory pressures of 0, 5, 10, and 15 cmH2O during mechanical ventilation, before and after induction of c-R/D by surfactant washout. 4DCT was post-processed for within-breath variation in atelectatic volume (Δ atelectasis) as a measure of c-R/D. Sound waveforms were evaluated for: 1) dynamic crackle energy (dCE): filtered crackle sounds (600–700 Hz); 2) fast Fourier transform area (FFT area): spectral content above 500 Hz in frequency and above −70 dB in amplitude in proportion to the total amount of sound above −70 dB amplitude; and 3) dynamic spectral coherence (dSC): variation in acoustical homogeneity over time. Parameters were analyzed for global, nondependent, central, and dependent lung areas. Results: In healthy lungs, negligible values of Δ atelectasis, dCE, and FFT area occurred. In lavage lung injury, the novel dCE parameter showed the best correlation to Δ atelectasis in dependent lung areas (R2 = 0.88) where c-R/D took place. dCE was superior to FFT area analysis for each lung region examined. The analysis of dSC could predict the lung regions where c-R/D originated. Conclusions: c-R/D is associated with the occurrence of fine crackle sounds as demonstrated by dCE analysis. Standardized computer-assisted analysis of dCE and dSC seems to be a promising method for depicting c-R/D

Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants

To assess the regional respiratory time constants of lung volume changes during stepwise lung recruitment before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. A stepwise oxygenation-guided recruitment procedure was performed before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. Electrical impedance tomography was used to continuously record changes in lung volume during the recruitment maneuver. Time constants were determined for all incremental and decremental pressure steps, using one-phase exponential decay curve fitting. Data were analyzed for the whole cross section of the chest and the ventral and dorsal lung regions separately. Before surfactant treatment, the time constants of the incremental pressure steps were significantly longer (median 27.3 s) than those in the decremental steps (16.1 s). Regional analysis showed only small differences between the ventral and dorsal lung regions. Following surfactant treatment, the time constants during decremental pressure steps almost tripled to 44.3 s. Furthermore, the time constants became significantly (p <0.01) longer in the dorsal (61.2 s) than into the ventral (40.3 s) lung region. Lung volume stabilization during stepwise oxygenation-guided lung recruitment in high-frequency oscillatory ventilated preterm infants with respiratory distress syndrome is usually completed within 5 min and is dependent on the position of ventilation on the pressure volume curve, the surfactant status, and the region of interest of the lun

Practical examination of bystanders performing Basic Life Support in Germany: a prospective manikin study

<p>Abstract</p> <p>Background</p> <p>In an out-of-hospital emergency situation bystander intervention is essential for a sufficient functioning of the chain of rescue. The basic measures of cardiopulmonary resuscitation (Basic Life Support – BLS) by lay people are therefore definitely part of an effective emergency service of a patient needing resuscitation. Relevant knowledge is provided to the public by various course conceptions. The learning success concerning a one day first aid course ("LSM" course in Germany) has not been much investigated in the past. We investigated to what extent lay people could perform BLS correctly in a standardised manikin scenario. An aim of this study was to show how course repetitions affected success in performing BLS.</p> <p>Methods</p> <p>The "LSM course" was carried out in a standardised manner. We tested prospectively 100 participants in two groups (<b>Group 1: </b>Participants with previous attendance of a BLS course; <b>Group 2: </b>Participants with no previous attendance of a BLS course) in their practical abilities in BLS after the course. Success parameter was the correct performance of BLS in accordance with the current ERC guidelines.</p> <p>Results</p> <p>Twenty-two (22%) of the 100 investigated participants obtained satisfactory results in the practical performance of BLS. Participants with repeated participation in BLS obtained significantly better results (<b>Group 1: </b>32.7% vs. <b>Group 2: </b>10.4%; p < 0.01) than course participants with no relevant previous knowledge.</p> <p>Conclusion</p> <p>Only 22% of the investigated participants at the end of a "LSM course" were able to perform BLS satisfactorily according to the ERC guidelines. Participants who had previously attended comparable courses obtained significantly better results in the practical test. Through regular repetitions it seems to be possible to achieve, at least on the manikin, an improvement of the results in bystander resuscitation and, consequently, a better patient outcome. To validate this hypothesis further investigations are recommended by specialised societies.</p