Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Feb 2019
ReviewRole of Pharmacologic Paralysis in Acute Respiratory Distress Syndrome.
The pharmacology and history of neuromuscular blockade in clinical care are complex, with multiple theoretical and observed potential benefits and potential harms. Past studies raised concern for long-term paresis, but more recent studies have not found evidence for harm, possibly due to changes in background care, neuromuscular blocking agent, and duration of blockade. Current use is highly variable, likely due to limited evidence for efficacy beyond short-term physiologic improvement and lingering concerns for harm. A recently completed large multicenter trial will provide further information on the role of pharmacologic paralysis in acute respiratory distress syndrome.
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Semin Respir Crit Care Med · Feb 2019
ReviewClinical Strategies to Prevent Acute Respiratory Distress Syndrome.
Acute respiratory distress syndrome (ARDS) remains an important clinical entity in the intensive care unit with a significant impact on morbidity and mortality. Effective therapeutic interventions are limited; thus current research focus has shifted from treatment to the prevention of this pulmonary syndrome. ⋯ Early identification of at-risk patients, prompt treatment of predisposing conditions, and adoption of evidence-based best practice including restrictive transfusion strategies, conservative fluid management, avoidance of large tidal volume ventilation, and aspiration precaution practices are key preventive strategies with demonstrated benefits. There are currently no effective pharmacological preventive strategies for ARDS.
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Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by noncardiogenic pulmonary edema. Despite five decades of basic and clinical research, there is still no effective pharmacotherapy for this condition and the treatment remains primarily supportive. It is critical to study the molecular and physiologic mechanisms that cause ARDS to improve our understanding of this syndrome and reduce mortality. ⋯ First, we will describe how pulmonary edema fluid accumulates in ARDS due to lung inflammation and increased alveolar endothelial and epithelial permeabilities. Next, we will review how pulmonary edema fluid is normally cleared in the uninjured lung, and describe how these pathways are disrupted in ARDS. Finally, we will explain how clinical trials and preclinical studies of novel therapeutic agents have further refined our understanding of this condition, highlighting, in particular, the study of mesenchymal stromal cells in the treatment of ARDS.
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Semin Respir Crit Care Med · Feb 2019
ReviewProne Positioning in Acute Respiratory Distress Syndrome.
Prone positioning is nowadays considered as one of the most effective strategies for patients with severe acute respiratory distress syndrome (ARDS). The evolution of the pathophysiological understanding surrounding the prone position closely follows the history of ARDS. ⋯ Indeed, the positive effects on oxygenation and CO2 clearance of the prone position are to be ascribed to a more homogeneous inflation-ventilation, to the lung/thoracic shape mismatch, and to the change of chest wall elastance. In the past 20 years, five major trials have tried, starting from different theories, hypotheses, and designs, to demonstrate the effectiveness of the prone position, which finally found its definitive place among the different ARDS supportive therapies.
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Semin Respir Crit Care Med · Feb 2019
ReviewDeconstructing ARDS Variability: Platelet Count, an ARDS Intermediate Phenotype and Novel Mediator of Genetic Effects in ARDS.
Genome-wide association studies (GWASs) in acute respiratory distress syndrome (ARDS) have been hampered by the heterogeneity of the clinical phenotypes and the large sample size requirement. As the limitations of these studies to uncover the complex genetic architecture of ARDS are evident, new approaches intended to reduce data complexity need to be applied. Intermediate phenotypes are mechanism-related manifestations of the disease, located closer to the genetic substrate than to disease phenotype, and therefore able to reflect more directly and more strongly the effect of causal genes. ⋯ By following this strategy, platelet count, a relevant intermediate quantitative trait in ARDS, has been recently identified as a novel mediator in the genetic contribution to ARDS risk and mortality. The use of intermediate phenotypes and causal inference are emerging methodological and statistical strategies that can help to overcome the limitations of traditional GWASs in ARDS. Moreover, these approaches can provide evidence for the mechanisms linking genes to ARDS and help to prioritize therapeutic targets for the treatment of this devastating syndrome.