Acute liver injury following acetaminophen administration does not activate atrophic pathways in the mouse diaphragm.

N-acetyl-para-amino phenol (APAP, usually named paracetamol), which is commonly used for its analgesic and antipyretic properties may lead to hepatotoxicity and acute liver damage in case of overdoses. Released cytokines and oxidative stress following acute liver damage may affect other organs' function notably the diaphragm, which is particularly sensitive to oxidative stress and circulating cytokines. We addressed this issue in a mouse model of acute liver injury induced by administration of APAP. C57BL/6J mice (each n = 8) were treated with N-acetyl-para-amino phenol (APAP) to induce acute drug caused liver injury and sacrificed 12 or 24 h afterwards. An untreated group served as controls. Key markers of inflammation, proteolysis, autophagy and oxidative stress were measured in diaphragm samples. In APAP treated animals, liver damage was proven by the enhanced serum levels of alanine aminotransferase and aspartate aminotransferase. In the diaphragm, besides a significant increase in IL 6 and lipid peroxidation, no changes were observed in key markers of the proteolytic, and autophagy signaling pathways, other inflammatory markers and fiber dimensions. The first 24 h of acute liver damage did not impair diaphragm atrophic pathways although it slightly enhanced IL-6 and lipid peroxidation. Whether longer exposure might affect the diaphragm needs to be addressed in future experiments.

[Weaning ward-different from the ICU?] / Weaningstation ­ was ist anders als auf der ICU?

Weaning from mechanical ventilation is generally not the most urgent topic on many ICUs, because acutely endangered patients are usually the staff's main focus. Nevertheless, even these patients whose underlying problem has been mostly solved-whether it was neurologic, internal or surgical-are in need of a structured weaning strategy. The aim of this weaning "road map" is ventilator independence, decannulation and regaining of muscular strength. Achieving of these aims needs a well-educated team of physicians, nurses, respiratory/physical therapists, logopedists and pychologists. Assessment of patient health status, including respiratory muscle function must be part of the overtaking procedure to be able to focus on the main problem that may be causative for the inability to wean so far. Every weaning unit must be able to organize the future treatment of patients (different ward inside the hospital, rehabilitation) or the transfer into a (ventilated) home care situation.

[Diaphragm dysfunction : Facts for clinicians]. / Diaphragmale Dysfunktion : Fakten für den Kliniker.

Diaphragm function is crucial for patient outcome in the ICU setting and during the treatment period. The occurrence of an insufficiency of the respiratory pump, which is predominantly formed by the diaphragm, may result in intubation after failure of noninvasive ventilation. Especially patients suffering from chronic obstructive pulmonary disease are in danger of hypercapnic respiratory failure. Changes in biomechanical properties and fiber texture of the diaphragm are further cofactors directly leading to a need for intubation and mechanical ventilation. After intubation and the following inactivity the diaphragm is subject to profound pathophysiologic changes resulting in atrophy and dysfunction. Besides this inactivity-triggered mechanism (termed as ventilator-induced diaphragmatic dysfunction) multiple factors, comorbidities, pharmaceutical agents and additional hits during the ICU treatment, especially the occurrence of sepsis, influence diaphragm homeostasis and can lead to weaning failure. During the weaning process monitoring of diaphragm function can be done with invasive methods - ultrasound is increasingly established to monitor diaphragm contraction, but further and better powered studies are in need to prove its value as a diagnostic tool.

[The role of colloids in intensive care medicine. Evidence instead of emotions]. / Stellenwert der Kolloide in der Intensivmedizin. Evidenz statt Emotion.

BACKGROUND: Besides albumin, which is gained from human donors, synthetic colloids have been playing a dominant role in treating patients in shock and are standard therapy in intensive care units (ICU). Since the publication of large randomized controlled trials indicating negative effects on renal function, their use has been questioned, especially for hydroxyethyl starch products. The preliminary assumption that these side effects are only existent in first or secondary generation starch fluids was proven incorrect. In fact, the use of hydroxyethyl starch products in critically ill patients is prohibited by the European Medicines Agency. CURRENT DISCUSSION AND INDICATIONS: Several methodological limitations exist in each of these trials that limit the evidence value of these investigations, although they served as the basis for the negative judgment of the European Medicines Agency. In addition, a large randomized controlled trial on the efficacy of gelatin is lacking. The use of colloids in ICU patients is indicated in cases where crystalloid volume therapy is inadequate. CONCLUSION: Especially during the first 6 h of sepsis, when aggressive volume therapy is decisive for patient outcome, colloids may be relevant to increase patient survival. The latest guideline on treatment with colloids has been published in the German S3 guideline "Intravascular volume therapy in adults."

A novel application for assessing diaphragmatic function by ultrasonic deformation analysis in noninvasively ventilated healthy young adults.

PURPOSE: Noninvasive pressure support ventilation is intended to relieve the load on respiratory muscles and to prevent exhaustion. This includes continuous positive airway pressure (CPAP) as well as pressure support ventilation (PSV). Speckle tracking echocardiography (STE) allows quantification of tissue deformation by tracing characteristic grayscale patterns, independent of the acquisition angle. The aim of the present study was to assess the applicability of using STE as a way to investigate diaphragm movement using deformation analysis as a parameter for respiratory workload. MATERIALS AND METHODS: Healthy male subjects (n = 13, 27 ±â€Š7 years) were treated while in a seated supine position with the following respirator settings: regular breathing, 5 mbar CPAP, CPAP + 5 / + 10 / + 15 mbar PSV. A 2 - 4 MhZ M5S phased array sector transducer was used on a Vivid E 9 (GE, Horton, Norway) to visualize the diaphragm. The inspiratory peak transverse strain was measured as a parameter of maximal inspiratory muscle workload and compared to the M-mode-based fractional thickening (FT). RESULTS: Both the FT and the transverse strain increased significantly under CPAP and PSV. The transverse strain correlated well with the FT (r = 0.753; p < 0.001). CONCLUSION: The results measured by STE were comparable to the M-mode-based measurements. The capturing of a larger diaphragmatic sample area and movement tracking possibly lead to higher precision compared to one-dimensional M-mode. The use of STE in patients might provide a reproducible, bedside method to analyze the respiratory workload. Due to the larger sampling area, it might prove superior to mere M-mode acquisition.

[Ventilator-induced diaphragm dysfunction : clinically relevant problem]. / Ventilatorinduzierte diaphragmale Dysfunktion : Klinisch relevantes Problem.

Mechanical ventilation is a life-saving intervention for patients with respiratory failure or during deep sedation. During continuous mandatory ventilation the diaphragm remains inactive, which activates pathophysiological cascades leading to a loss of contractile force and muscle mass (collectively referred to as ventilator-induced diaphragm dysfunction, VIDD). In contrast to peripheral skeletal muscles this process is rapid and develops after as little as 12 h and has a profound influence on weaning patients from mechanical ventilation as well as increased incidences of morbidity and mortality. In recent years, animal experiments have revealed pathophysiological mechanisms which have been confirmed in humans. One major mechanism is the mitochondrial generation of reactive oxygen species that have been shown to damage contractile proteins and facilitate protease activation. Besides atrophy due to inactivity, drug interactions can induce further muscle atrophy. Data from animal research concerning the influence of corticosteroids emphasize a dose-dependent influence on diaphragm atrophy and function although the clinical interpretation in intensive care patients (ICU) patients might be difficult. Levosimendan has also been proven to increase diaphragm contractile forces in humans which may prove to be helpful for patients experiencing difficult weaning. Additionally, antioxidant drugs that scavenge reactive oxygen species have been demonstrated to protect the diaphragm from VIDD in several animal studies. The translation of these drugs into the IUC setting might protect patients from VIDD and facilitate the weaning process.

A laboratory comparison of the performance of the buddy lite™ and enFlow™ fluid warmers.

Maintenance of normothermia is crucial to avoid patient morbidity. Newly released fluid warming devices have become smaller in size, but this change might impair efficacy. We performed an evaluation of the buddy lite™ and enFlow™ fluid warmers. We measured inflow and outlet temperatures of the devices at flow rates between 25 and 100 ml.min(-1) using saline at room temperature or cooled to 10 °C. At a flow rate of 25 ml.min(-1) , the outlet temperature of the buddy lite was significantly higher than that of the enFlow (p < 0.0001), but at flow rates of 75 and 100 ml.min(-1) , it was significantly lower (p < 0.0001). This pattern was the same for both room temperature and cooled saline. There was a significant drop in the temperature of saline along the length of a 1-m outflow tube. We conclude that both devices provide effective fluid warming at a low flow rate, although the heating capability of the buddy lite is limited at high flow rates.

[Ventilation in acute respiratory distress. Lung-protective strategies]. / Beatmung beim akuten Lungenversagen. Lungenprotektive Strategien.

Ventilation of patients suffering from acute respiratory distress syndrome (ARDS) with protective ventilator settings is the standard in patient care. Besides the reduction of tidal volumes, the adjustment of a case-related positive end-expiratory pressure and preservation of spontaneous breathing activity at least 48 h after onset is part of this strategy. Bedside techniques have been developed to adapt ventilatory settings to the individual patient and the different stages of ARDS. This article reviews the pathophysiology of ARDS and ventilator-induced lung injury and presents current evidence-based strategies for ventilator settings in ARDS.

[Positive end-expiratory pressure : adjustment in acute lung injury]. / Positiver endexspiratorischer Druck : Einstellung bei respiratorischer Insuffizienz.

Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment.