Erik K. Hartmann

Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model

IntroductionCyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO2 (ΔpaO2). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RRind) on intra-tidal amplitude of Δ paO2 and on average paO2 in saline-lavaged pigs.MethodsAcute lung injury was induced by bronchoalveolar lavage in 16 anaesthetized pigs. R/D was induced and measured by a fast-responding intra-aortic probe measuring paO2. Ventilatory interventions (RRind (n = 8) versus extrinsic PEEP (n = 8)) were applied for 30 minutes to reduce Δ paO2. Haemodynamics, spirometry and Δ paO2 were monitored and the Ventilation/Perfusion distributions were assessed by multiple inert gas elimination. The main endpoints average and Δ paO2 following the interventions were analysed by Mann-Whitney-U-Test and Bonferronis correction. The secondary parameters were tested in an explorative manner.ResultsBoth interventions reduced Δ paO2. In the RRind group, ΔpaO2 was significantly smaller (P < 0.001). The average paO2 continuously decreased following RRind and was significantly higher in the PEEP group (P < 0.001). A sustained difference of the ventilation/perfusion distribution and shunt fractions confirms these findings. The RRind application required less vasopressor administration.ConclusionsDifferent recruitment kinetics were found compared to previous small animal models and these differences were primarily determined by kinetics of end-expiratory collapse. In this porcine model, respiratory rate and increased PEEP were both effective in reducing the amplitude of paO2 oscillations. In contrast to a recent study in a small animal model, however, increased respiratory rate did not maintain end-expiratory recruitment and ultimately resulted in reduced average paO2 and increased shunt fraction.

An inhaled tumor necrosis factor‐alpha‐derived TIP peptide improves the pulmonary function in experimental lung injury

The lectin‐like domain of TNF‐α enhances the fluid clearance across the alveolar barrier. For experimental purposes, the lectin‐like domain can be mimicked by a synthetic peptide representing the TIP‐motif of TNF‐α. The present study aims to assess the acute effect of TIP on the pulmonary function in a porcine model of acute respiratory distress syndrome (ARDS).

Influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome

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 (&Dgr;PaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon &Dgr;PaO2 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 &Dgr;PaO2 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.

Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment

BACKGROUND Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation. METHODS In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed at baseline and during cyclic R/D. STATISTICS frequency domain analysis, the Mann-Whitney test, linear models to test the influence of Pa(O(2)) and systolic arterial pressure (SAP) oscillations on cerebral measurements. RESULTS Parameters [mean (SD)] remained stable during baseline. Pa(O(2)) oscillations [10.6 (8) kPa, phase(reference)], systemic arterial pressure (SAP) oscillations [20 (9) mm Hg, phase(Pa(O(2))-SAP) -33 (72)°], and Sp(O(2))oscillations [1.9 (1.7)%, phase(Pa(O(2))-Sp(O(2))) 264 (72)°] were detected during lung R/D at 1.0. Pa(O(2)) oscillations decreased [2.7 (3.5) kPa, P=0.0008] and Sp(O(2)) oscillations increased [6.8 (3.9)%, P=0.0014] at F(I(O(2))) 0.3. In the brain, synchronized Pbr(O(2)) oscillations [0.6 (0.4) kPa, phase(Pa(O(2))-Pbr(O(2))) 90 (39)°], Sbr(O(2)) oscillations [4.1 (1.5)%, phase(Pa(O(2))-Sbr(O(2))) 182 (54)°], and CBF oscillations [198 (176) AU, phase(Pa(O(2))-CBF) 201 (63)°] occurred that were dependent on Pa(O(2)) and SAP oscillations. CONCLUSIONS Pa(O(2)) oscillations caused by cyclic R/D are transmitted to the cerebral microcirculation in a porcine model of ALI. These cyclic oxygen alterations could play a role in the crosstalk of acute lung and brain injury.

Low tidal volume pressure support versus controlled ventilation in early experimental sepsis in pigs

BackgroundIn moderate acute respiratory distress syndrome (ARDS) several studies support the usage of assisted spontaneous breathing modes. Only limited data, however, focus on the application in systemic sepsis and developing lung injury. The present study examines the effects of immediate initiation of pressure support ventilation (PSV) in a model of sepsis-induced ARDS.Methods18 anesthetized pigs received a two-staged continuous lipopolysaccharide infusion to induce lung injury. The animals were randomly assigned to PSV or volume controlled (VCV) lung protective ventilation (tidal volume each 6 ml kg-1, n = 2x9) over six hours. Gas exchange parameters, hemodynamics, systemic inflammation, and ventilation distribution by multiple inert gas elimination and electrical impedance tomography were assessed. The post mortem analysis included histopathological scoring, wet to dry ratio, and alveolar protein content.ResultsWithin six hours both groups developed a mild to moderate ARDS with comparable systemic inflammatory response and without signs of improving gas exchange parameters during PSV. The PSV group showed signs of more homogenous ventilation distribution by electrical impedance tomography, but only slightly less hyperinflated lung compartments by multiple inert gas elimination. Post mortem and histopathological assessment yielded no significant intergroup differences.ConclusionsIn a porcine model of sepsis-induced mild ARDS immediate PSV was not superior to VCV. This contrasts with several experimental studies from non-septic mild to moderate ARDS. The present study therefore assumes that not only severity, but also etiology of lung injury considerably influences the response to early initiation of PSV.

Assessment of Regional Ventilation Distribution: Comparison of Vibration Response Imaging (VRI) with Electrical Impedance Tomography (EIT)

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 R2 = 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 R2 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.

A novel technique for monitoring of fast variations in brain oxygen tension using an uncoated fluorescence quenching probe (Foxy AL-300).

Background: A novel uncoated fluorescence quenching probe allows fast measurement of oxygen tension in vessels and tissue. The present study reports the first use of the technology for dual measurements of arterial (paO2) and brain tissue oxygen tension (ptiO2) during hypoxic challenge in a pig model. Methods: Eight pigs were anesthetized using fentanyl and propofol. Fluorescence quenching pO2 probes (Foxy AL-300, Ocean Optics, Dunedin, FL) were placed in the ascending aorta (Foxy-paO2) and subcortically at 14 mm in brain tissue (Foxy-ptiO2). As reference, a clark-type electrode probe (Licox-ptiO2) was placed into brain tissue close to the Foxy probe (Licox, Integra Neurosciences, Plainsboro, NJ). Measurements were taken at baseline (FiO2 1.0), during episodes of apnea, and during recovery (FiO2 1.0). Statistics: descriptive results. Results: Individual Foxy-paO2, Foxy-ptiO2, and Licox-ptiO2 courses were related to episodes of apnea. The response time of the Foxy measurements was 10 Hz. Baseline values at FiO2 1.0 were Foxy-paO2 520±120 mm Hg, Foxy-ptiO2 62±24 mm Hg, and Licox-ptiO2 55±29 mm Hg; apnea values were Foxy-paO2 64±10 mm Hg, Foxy-ptiO2 37±12 mm Hg, and Licox-ptiO2 31±16 mm Hg; recovery values at FiO2 1.0 were Foxy-paO2 478±98 mm Hg, Foxy-ptiO2 78±26 mm Hg, and Licox-ptiO2 62±32 mm Hg. Conclusions: The present study demonstrates the feasibility of pO2 measurements in macrocirculation and cerebral microcirculation using a novel uncoated fluorescence quenching probe. The technology allows for real-time investigation of pO2 changes at a temporal resolution of 0.05 to 10 Hz.

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation

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.

PaO2 oscillations caused by cyclic alveolar recruitment can be monitored in pig buccal mucosa microcirculation

Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO2) oscillations within the respiratory cycle. It remains unknown, however, if these PaO2 oscillations are transmitted to the microcirculation. The present study investigates if PaO2 oscillations can be detected in the pig buccal mucosa microcirculation.

Novel technologies to detect atelectotrauma in the injured lung

ABSTRACT Cyclical recruitment and derecruitment of lung parenchyma (R/D) remains a serious problem in ALI/ARDS patients, defined as atelectotrauma. Detection of cyclical R/D to titrate the optimal respiratory settings is of high clinical importance. Image-based technologies that are capable of detecting changes of lung ventilation within a respiratory cycle include dynamic computed tomography (dCT), synchrotron radiation computed tomography (SRCT), and electrical impedance tomography (EIT). Time-dependent intra-arterial oxygen tension monitoring represents an alternative approach to detect cyclical R/D, as cyclical R/D can result in oscillations of PaO2 within a respiratory cycle. Continuous, ultrafast, on-line in vivo measurement of PaO2 can be provided by an indwelling PaO2 probe. In addition, monitoring of fast changes in SaO2 by pulse oximetry technology at the bedside could also be used to detect those fast changes in oxygenation.