Seminars in respiratory and critical care medicine
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Because acute lung injury (ALI) may arise from diverse and heterogeneous clinical insults, monitoring strategies for patients with ALI are heterogeneous as well. This review divides the monitoring strategies for ALI into three distinct phases. The "at-risk phase" is the period in which patients are at risk for ALI, and interventions may be applied to minimize or eliminate this risk. ⋯ The primary goals are to optimize fluid resuscitation to prevent organ dysfunction, including ALI, and if ALI occurs to additional optimize fluid balance vis-à-vis the lung. By judicious application of invasive hemodynamic monitoring, particularly in its more modern iterations, clinicians can optimize the ebb and flow phases common to critically ill patients. This is vitally important given our current and growing understanding of the relationship between fluid balance and important clinical outcomes, multiple organ dysfunction syndrome, and mortality.
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The overarching goal of positive pressure mechanical ventilation is to provide adequate gas exchange support while not causing harm. Indeed, positive pressure mechanical ventilators are only support technologies, not therapeutic technologies. As such they cannot be expected to "cure" disease; they can only "buy time" for other therapies (including the patient's own defenses) to work. ⋯ In recent decades several novel or unconventional approaches to providing mechanical ventilatory support have been introduced. For these to be considered of value, however, it would seem reasonable that they address important clinical challenges and be shown to improve important clinical outcomes (e.g., mortality, duration of ventilation, sedation needs, complications). This article focuses on challenges facing clinicians in providing mechanical ventilatory support and assesses several novel approaches introduced over the last 2 decades in the context of these challenges.
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Lung transplantation is the ultimate treatment option for patients with end-stage lung disease. Chronic rejection, in the form of bronchiolitis obliterans syndrome, and noncytomegalovirus infections are the major causes of morbidity and mortality beyond the first year after transplantation. Most lung transplant recipients are treated lifelong with a three-drug immunosuppression regimen consisting of a calcineurin inhibitor, an antimetabolite, and low-dose corticosteroids. ⋯ Additionally, the role of mammalian target of rapamycin (mTOR) inhibitors in the treatment of lung transplant recipients and the utility of azithromycin to treat and prevent bronchiolitis obliterans syndrome are areas of active investigation. This review discusses induction and traditional maintenance immunosuppressive agents and regimens and the evidence that exists to help guide therapy. Newer research involving the use of mTOR inhibitors in place of calcineurin inhibitors or antimetabolites and azithromycin for the treatment and prevention of bronchiolitis obliterans syndrome is also explored.
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Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. ⋯ Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.
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Primary graft dysfunction (PGD) is a syndrome encompassing a spectrum of mild to severe lung injury that occurs within the first 72 hours after lung transplantation. PGD is characterized by pulmonary edema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. In recent years, new knowledge has been generated on risks and mechanisms of PGD. ⋯ Improved methods of reducing PGD risk and efforts to safely expand the pool are being developed. Ex vivo lung perfusion is a strategy that may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review details recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers, and state-of-the-art technical developments affecting PGD.