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Introduction Cyclic 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. Methods Acute 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 Bonferroni's correction. The secondary parameters were tested in an explorative manner. Results Both 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. Conclusions Different 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.

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

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

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

Background Perioperative high-dose oxygen (O2) exposure can cause hyperoxia. While the effect of constant hyperoxia on the vascular endothelium has been investigated to some extent, the impact of cyclic hyperoxia largely remains unknown. We hypothesized that cyclic hyperoxia would induce more injury than constant hyperoxia to human umbilical vein endothelial cells (HUVECs). Methods HUVECs were exposed to cyclic hyperoxia (5–95% O2) or constant hyperoxia (95% O2), normoxia (21% O2), and hypoxia (5% O2). Cell growth, viability (Annexin V/propidium iodide and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT) lactate dehydrogenase (LDH), release, cytokine (interleukin, IL and macrophage migration inhibitory factor, MIF) release, total antioxidant capacity (TAC), and superoxide dismutase activity (SOD) of cell lysate were assessed at baseline and 8, 24, and 72 h. A signal transduction pathway finder array for gene expression analysis was performed after 8 h. Results Constant and cyclic hyperoxia-induced gradually detrimental effects on HUVECs. After 72 h, constant or cyclic hyperoxia exposure induced change in cytotoxic (LDH +12%, P = 0.026; apoptosis +121/61%, P < 0.01; alive cells −15%, P < 0.01; MTT −16/15%, P < 0.01), inflammatory (IL-6 +142/190%, P < 0.01; IL-8 +72/43%, P < 0.01; MIF +147/93%, P < 0.01), or redox-sensitive (SOD +278%, TAC-25% P < 0.01) markers. Gene expression analysis revealed that constant and cyclic hyperoxia exposure differently activates oxidative stress, nuclear factor kappa B, Notch, and peroxisome proliferator-activated receptor pathways. Conclusions Extreme hyperoxia exposure induces inflammation, apoptosis and cell death in HUVECs. Although our findings cannot be transferred to clinical settings, results suggest that hyperoxia exposure may cause vascular injury that could play a role in determining perioperative outcome.

Cyclic recruitment and derecruitment (R/D) of lung parenchyma during mechanical ventilation are responsible for atelectrauma. Theoretically, cyclic R/D can lead to varying degrees of pulmonary shunt fraction throughout the respiratory cycle. Measurements of dynamic pulmonary shunt fraction could help in assessing the degree of cylic R/D. However, common methods of measuring pulmonary shunt do not allow for dynamic serial measurements during one respiratory cycle. In this study, we measured serial dynamic pulmonary shunt fractions during one breathing cycle and investigated the effect of positive end-expiratory pressure (PEEP) on cyclic R/D in artificially ventilated pigs before and after saline washout induced acute lung injury.

Case report A 42-year old healthy Caucasian male contacted our malignant hyperthermia (MH) hotline due to cramps and muscle pain one week after moderate exercise. He was already diagnosed MHS in 1988 by in vitro contracture test (IVCT), after a suspected MH episode during general anaesthesia. At present, he reported severe muscle pain and cramps in both upper legs. The discomfort has started after moderate endurance training with mild muscle soreness for 2 days. On the 3 day, pain increased, accompanied by severe muscle cramps in both upper legs. Symptoms were worsened by cold temperature. Due to pain, muscle weakness and swelling in both upper legs, he had sought medical attention on day 5 in a surgical outpatient clinic, where an ultrasound examination showed a “homogenous increase in muscle density of both quadriceps muscles”. No laboratory tests except d-dimer were performed and after exclusion of an acute thromboembolic event, the patient was dismissed. Due to ongoing pain, he contacted our MH-Hotline 7 days after the exercise. He still felt sick and reported darker urine during the past 3 days. Body temperature was not yet measured. His general practitioner had already taken a blood examination one hour before the telephone call. One day later, laboratory analysis was available and showed a CPK of 39,628 U/l and myoglobin of 2,863 ng/ml, consistent with rhabdomyolysis. Also liver enzymes were elevated, but kidney function and potassium were normal. The patient reported a body temperature of 37.5°C in the morning. Due to the high CPK levels 7 days after exercise (normally, peak levels are expected within 48 to 96 h), we recommended an immediate admission to our unit and decided to start with dantrolene 2.5 mg/kg IV. After the initial dose of dantrolene he was admitted to an intermediate care unit for the first 24h. Dantrolene was not continued since he was clinically stable. No clinical signs of a compartment syndrome could be detected. Pain continuously decreased and laboratory parameters slowly returned to normal within the next 2 weeks except of a CPK of 330 U/l. Body temperature and kidney function remained normal during the whole period. Any other reason for rhabdomyolysis than MHS diagnosis, i.e. viral or bacterial infection, hypothyreosis, medication, drugs or dietary supplements could be ruled out. A MRI examination showed an inhomogenous enhancement of contrast medium and edema of both quadriceps muscles. The patient was dismissed from hospital 3 days later, additional genetic testing has been planned. Unfortunately, previous CPK levels of the patient were unknown and in 1988, when IVCT was performed, histology was not regularly done.