Hans-Dieter Walmrath

Alveolar surfactant and adult respiratory distress syndrome

SummaryThe adult respiratory distress syndrome (ARDS) is characterized by extended inflammatory processes in the lung microvascular, interstitial, and alveolar compartments, resulting in vasomotor disturbances, plasma leakage, cell injury, and complex gas exchange disturbances. Abnormalities in the alveolar surfactant system have long been implicated in the pathogenetic sequelae of this life-threatening syndrome. This hypothesis is supported by similarities in pulmonary failure between patients with ARDS and preterm babies with infant respiratory distress syndrome, known to be triggered primarily by lack of surfactant material. Mechanisms of surfactant alterations in ARDS include: (a) lack of surface-active compounds (phospholipids, apoproteins) due to reduced generation/release by diseased pneumocytes or to increased loss of material (this feature includes changes in the relative composition of the surfactant phospholipid and/or apoprotein profiles); (b) inhibition of surfactant function by plasma protein leakage (inhibitory potencies of different plasma proteins have been defined); (c) “incorporation” of surfactant phospholipids and apoproteins into polymerizing fibrin upon hyaline membrane formation; and (d) damage/inhibition of surfactant compounds by inflammatory mediators (proteases, oxidants, nonsurfactant lipids). Alterations in alveolar surfactant function may well contribute to a variety of pathophysiological key events encountered in ARDS. These include decrease in compliance, ventilation-perfusion mismatch including shunt flow due to altered gas flow distribution (atelectasis, partial alveolar collapse, small airway collapse), and lung edema formation. Moreover, more speculative at the present time, surfactant abnormalities may add to a reduction in alveolar host defense competence and an upregulation of inflammatory events under conditions of ARDS. Persistent atelectasis of surfactant-deficient and in particular fibrin-loaded alveoli may represent a key event to trigger fibroblast proliferation and fibrosis in late ARDS (“collapse induration”). Overall, the presently available data on surfactant abnormalities in ARDS lend credit to therapeutic trials with transbronchial surfactant administration. In addition to the classical goals of replacement therapy defined for preterm infants (rapid improvement in lung compliance and gas exchange), this approach will have to consider its impact on host defense competence and inflammatory and proliferative processes when applied in adults with respiratory failure.

Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia

Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

Clinical Aspects of Acute Lung Insufficiency (ALI/TRALI)

Acute respiratory distress syndrome (ARDS) is a common clinical disorder caused by a variety of direct and indirect injuries to the lung, characterized by alveolar epithelial and endothelial injury resulting in damage to the pulmonary alveolar-capillary barrier. The cardinal clinical feature of ARDS, refractory arterial hypoxemia, is the result of protein-rich alveolar edema with impaired surfactant function, due to vascular leakage and vascular dysfunction with consequently impaired matching of ventilation to perfusion. Since its first description in 1967, considerable knowledge concerning the pathogenesis of ARDS has been obtained, however, a plethora of questions remain. Better understanding of the pathophysiology of ARDS has lead to the development of novel therapies, pharmacological strategies, and advances in mechanical ventilation. However, lung-protective ventilation is the only confirmed option in ARDS management improving survival, and few other therapies have translated into improved oxygenation or reduced ventilation time. But despite improvement in our understanding of the therapy and supportive care for patients with ARDS, mortality remains high. It is the purpose of this article to provide an overview of the definition, clinical features, and pathogenesis of ARDS, and to present and discuss therapeutic options currently available in order to effectively treat this severe disorder.

Immunomodulation by lipid emulsions in pulmonary inflammation: a randomized controlled trial

IntroductionAcute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation.MethodsIn a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally.ResultsIn volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice.ConclusionsAfter infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo.Trial registrationDRKS00006131 at the German Clinical Trial Registry, 2014/05/14

Ernährung und Immunonutrition bei Sepsis

ZusammenfassungDie Ernährungstherapie bei Intensivpatienten ist mehr als die Zufuhr von Kalorien. Nicht alle Konzepte der Ernährung aus der allgemeinen Intensivmedizin sind direkt auf septische Patienten übertragbar. Eine enge Glukosekontrolle durch intensivierte Insulintherapie, erfolgreich bei postoperativen Intensivpatienten angewandt, muss für septische Patienten modifiziert werden. Die Ernährung mit enteraler Immunonutrition, die bei postoperativen Patienten zu einer Verminderung der Liegezeiten führte, kann bei Patienten mit schwerer Sepsis zu einer Erhöhung der Mortalität führen. Für die parenterale Ernährung stehen weiter entwickelte Lipidemulsionen zur Verfügung, die wahrscheinlich Vorteile für den septischen Patienten mit sich bringen. Die intravenöse Supplementierung von langfristig rein parenteral ernährten Intensivpatienten mit Glutamin kann möglicherweise die Sterblichkeit verringern. Insgesamt ist eine individuell optimierte und an die Erkrankung angepasste Ernährung als adjunkte Therapieform ein wichtiger Baustein des Gesamttherapiekonzepts der Sepsis.AbstractNutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.Nutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.

Ernährung und Immunonutrition bei Sepsis@@@Nutrition and immunonutrition in septic patients

ZusammenfassungDie Ernährungstherapie bei Intensivpatienten ist mehr als die Zufuhr von Kalorien. Nicht alle Konzepte der Ernährung aus der allgemeinen Intensivmedizin sind direkt auf septische Patienten übertragbar. Eine enge Glukosekontrolle durch intensivierte Insulintherapie, erfolgreich bei postoperativen Intensivpatienten angewandt, muss für septische Patienten modifiziert werden. Die Ernährung mit enteraler Immunonutrition, die bei postoperativen Patienten zu einer Verminderung der Liegezeiten führte, kann bei Patienten mit schwerer Sepsis zu einer Erhöhung der Mortalität führen. Für die parenterale Ernährung stehen weiter entwickelte Lipidemulsionen zur Verfügung, die wahrscheinlich Vorteile für den septischen Patienten mit sich bringen. Die intravenöse Supplementierung von langfristig rein parenteral ernährten Intensivpatienten mit Glutamin kann möglicherweise die Sterblichkeit verringern. Insgesamt ist eine individuell optimierte und an die Erkrankung angepasste Ernährung als adjunkte Therapieform ein wichtiger Baustein des Gesamttherapiekonzepts der Sepsis.AbstractNutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.Nutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.

Lung-Kidney Cross-Talk

Abstract Awareness of the multifaceted lung and kidney interactions in the critically ill has increased considerably. Cardiogenic and noncardiogenic pulmonary edema represent two entities of pulmonary edema and differ significantly in terms of alveolar fluid clearance. Acute lung injury describes the breakdown of normal lung architecture with development of a high-permeability noncardiogenic pulmonary edema resulting from an inflammation/oxidant-mediated injury to the alveolar-capillary barrier and downregulation of the epithelial active ion transport system. Acute kidney injury is the most common organ dysfunction in patients with acute respiratory distress syndrome. It may develop as a result of blood gas disturbances that compromise renal blood flow and renal compensatory mechanisms; pulmonary hypertension, which may aggravate renal impairment by causing renal congestion and tissue edema; and mechanical ventilation–induced alterations, including systemic release of mediators, all which promote end-organ cell injury. Acute kidney injury, on the other hand, may initiate and perpetuate lung injury resulting from fluid overload and the systemic release of mediators that promote increased pulmonary vascular permeability, lung inflammation, and apoptosis, and breakdown of the transepithelial electrolyte and water transport, ultimately leading to respiratory failure. It is hoped that an in-depth understanding of the factors influencing lung-kidney interactions will encourage physicians to explore and develop new strategies for the benefit of the patient.

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Nutrition and immunonutrition in septic patients

ZusammenfassungDie Ernährungstherapie bei Intensivpatienten ist mehr als die Zufuhr von Kalorien. Nicht alle Konzepte der Ernährung aus der allgemeinen Intensivmedizin sind direkt auf septische Patienten übertragbar. Eine enge Glukosekontrolle durch intensivierte Insulintherapie, erfolgreich bei postoperativen Intensivpatienten angewandt, muss für septische Patienten modifiziert werden. Die Ernährung mit enteraler Immunonutrition, die bei postoperativen Patienten zu einer Verminderung der Liegezeiten führte, kann bei Patienten mit schwerer Sepsis zu einer Erhöhung der Mortalität führen. Für die parenterale Ernährung stehen weiter entwickelte Lipidemulsionen zur Verfügung, die wahrscheinlich Vorteile für den septischen Patienten mit sich bringen. Die intravenöse Supplementierung von langfristig rein parenteral ernährten Intensivpatienten mit Glutamin kann möglicherweise die Sterblichkeit verringern. Insgesamt ist eine individuell optimierte und an die Erkrankung angepasste Ernährung als adjunkte Therapieform ein wichtiger Baustein des Gesamttherapiekonzepts der Sepsis.AbstractNutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.Nutrition in septic patients is more than just caloric support. Not all nutritional concepts in general intensive care may be applied to septic patients. A tight glycemic control successfully used in post-operative intensive care patients has to be modified for the septic patient. Enteral immunonutrition leading to reduced length of stay in post-operative patients may be associated with increased mortality in patients suffering from severe sepsis. Newly developed lipid emulsions for parenteral nutrition became available. Application of these emulsions may prove to be beneficial in septic patients. An intravenous supplementation with glutamine of long-term exclusively parenterally fed intensive care patients may reduce their mortality. A nutrition individually optimized and adapted to the severity of the disease is considered to be an adjunct therapeutic measure in the treatment concept in sepsis.

Lungenembolie und Lungeninfarkt

Haufigste Ursache einer Lungenembolie (Thromboembolie) ist die Verschleppung von thrombotischem Material aus den tiefen Beinvenen in die pulmonale Strombahn. Sowohl die Lungenembolie als auch die tiefe Beinvenenthrombose stellen aber klinisch meist unerwartete Ereignisse dar, die zu einer Verzogerung der diagnostischen und therapeutischen Masnahmen fuhren konnen und somit entscheidend zu Morbiditat und Letalitat beitragen. Epidemiologische Daten zur Inzidenz der Lungenembolie in Deutschland liegen nicht vor. Ubertragt man jedoch die nordamerikanischen Daten, so kann man von einer Inzidenz von 100.000 bis 150.000 Fallen pro Jahr ausgegangen werden.