Objectives: To test the hypothesis that nebulized epinephrine ameliorates pulmonary dysfunction by dual action—bronchodilation (?2-adrenergic receptor agonism) and attenuation of airway hyperemia (?1-adrenergic receptor agonism) with minimal systemic effects. Design: Randomized, controlled, prospective, and large animal translational studies. Setting: University large animal ICU. Subjects: Twelve chronically instrumented sheep. Interventions: The animals were exposed to 40% total body surface area third degree skin flame burn and 48 breaths of cooled cotton smoke inhalation under deep anesthesia and analgesia. The animals were then placed on a mechanical ventilator, fluid resuscitated, and monitored for 48 hours in a conscious state. After the injury, sheep were randomized into two groups: 1) epinephrine, nebulized with 4 mg of epinephrine every 4 hours starting 1 hour post injury, n = 6; or 2) saline, nebulized with saline in the same manner, n = 6. Measurements and Main Results: Treatment with epinephrine had a significant reduction of the pulmonary transvascular fluid flux to water (p < 0.001) and protein (p < 0.05) when compared with saline treatment from 12 to 48 hours and 36 to 48 hours, respectively. Treatment with epinephrine also reduced the systemic accumulation of body fluids (p < 0.001) with a mean of 1,410 ± 560 mL at 48 hours compared with 3,284 ± 422 mL of the saline group. Hemoglobin levels were comparable between the groups. Changes in respiratory system dynamic compliance, mean airway pressure, PaO2/FiO2 ratio, and oxygenation index were also attenuated with epinephrine treatment. No considerable systemic effects were observed with epinephrine treatment. Conclusions: Nebulized epinephrine should be considered for use in future clinical studies of patients with burns and smoke inhalation injury.

Objective: This special article will review the history of blood glucose meter hospital use and current issues surrounding their use in this patient population. Study Selection: Secondary to accuracy concerns that have been known, but likely underappreciated for many years, the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services are moving toward eliminating current blood glucose meters for use with critically ill patients. Data Sources: Recent guidance from the U.S. Food and Drug Administration and Centers for Medicare and Medicaid Services along with several recent publications will be used as the primary data sources. Data Extraction: U.S. Food and Drug Administration, Centers for Medicare and Medicaid Services communications combined with recent interpretation of this guidance were used to provide this overview. Data Synthesis: Centers for Medicare and Medicaid Services have issued a temporary moratorium on the prohibition of the use of blood glucose meters in the critically ill. They have not given a deadline for the moratorium or solicited comments. Conclusions: Physicians who care for critically ill patients need to be cognizant of the accuracy and interference limitations of blood glucose meters and aware of the current regulatory situation.

Objective: To report a series of three patients who received simultaneous circulatory support with both veno-arterial extracorporeal membrane oxygenation and intra-aortic balloon pump and subsequently developed spinal cord infarction, and present a brief review of the relevant literature. Data Sources: Hospital medical records and MEDLINE and PubMed databases. Study Selection: Any patient who developed lower limb neurologic symptoms during a period of concurrent venoarterial extracorporeal membrane oxygenation and intra-aortic balloon pump support, with subsequent MRI changes involving the spinal cord, from 2006 (the year of institution of venoarterial extracorporeal membrane oxygenation in our ICU) to 2014. Data Extraction: Patient records were retrospectively reviewed. Medical databases were searched for any literature linking intra-aortic balloon pump and/or venoarterial extracorporeal membrane oxygenation with neurologic injury of the lower limbs. Data Synthesis: Three female patients presented in cardiogenic shock or arrest requiring circulatory support. Intra-aortic balloon pump was inserted, and peripheral veno-arterial extracorporeal membrane oxygenation was initiated with subsequent loss of native ejection in each case. Neurologic signs were noted clinically, and subsequent imaging demonstrated spinal cord infarction and small aortic size for all three patients. Conclusions: The timeline of events suggests a causal relation between intra-aortic balloon pump, veno-arterial extracorporeal membrane oxygenation, and significant neurologic deficits. This is likely due to hypoperfusion of the spinal cord, which is multifactorial in origin, including small aortic calibre, low cardiac output states, high vasopressor requirements causing vasospasm of the artery of Adamkiewicz, occlusion of retrograde oxygenated blood flow from peripheral veno-arterial extracorporeal membrane oxygenation due to intra-aortic balloon pump being in situ, and possible thromboembolic phenomena. The thoracic spinal cord is intrinsically susceptible to ischemia due to the anatomy of the arterial supply, which is described here. We identify several risk factors and make several recommendations to avoid this rare but catastrophic complication in the future. We also suggest interventions should this challenging complication be identified.

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Purpose of review: This article discusses recently published articles reporting the incidence and outcome of patients with the acute respiratory distress syndrome (ARDS). This is a difficult task since there is a marked variability regarding the methodology of the few, large epidemiological, and observational studies on ARDS. Recent findings: The review will mainly focus on publications from the past 18 months. We have reviewed new epidemiological studies reporting population-based incidence of ARDS. Also, we have reviewed the data on survival reported in observational and randomized controlled trials, discussed how the current ARDS definition modifies the true incidence of ARDS, and briefly mentioned recent approaches that appear to improve ARDS outcome. Summary: On the basis of current evidence, it seems that the incidence and overall hospital mortality of ARDS has not changed substantially in the last decade. Independent of the definition used for identification of ARDS patients, reported population-based incidence of ARDS is an order of magnitude lower in Europe than in the USA. Current hospital mortality of combined moderate and severe ARDS reported in observational studies is greater than 40%.

Purpose of review: The optimal strategy for assessing and preventing ventilator-induced lung injury in the acute respiratory distress syndrome (ARDS) is controversial. Recent investigative efforts have focused on personalizing ventilator settings to individual respiratory mechanics. This review examines the strengths and weaknesses of using transpulmonary pressure measurements to guide ventilator management in ARDS. Recent findings: Recent clinical studies suggest that adjusting ventilator settings based on transpulmonary pressure measurements is feasible, may improve oxygenation, and reduce ventilator-induced lung injury. Summary: The measurement of transpulmonary pressure relies upon esophageal manometry, which requires the acceptance of several assumptions and potential errors. Notably, this includes the ability of localized esophageal pressures to represent global pleural pressure. Recent investigations demonstrated improved oxygenation in ARDS patients when positive end-expiratory pressure was adjusted to target specific end-inspiratory or end-expiratory transpulmonary pressures. However, there are different methods for estimating transpulmonary pressure and different goals for positive end-expiratory pressure titration among recent studies. More research is needed to refine techniques for the estimation and utilization of transpulmonary pressure to guide ventilator settings in ARDS patients.

Purpose of review: Acute respiratory distress syndrome (ARDS) is a devastating disease process with a 40% mortality rate, and for which there is no therapy. Stem cells are an exciting potential therapy for ARDS, and are currently the subject of intensive ongoing research efforts. We review data concerning the therapeutic promise of cell-based therapies for ARDS. Recent findings: Recent experimental studies suggest that cell-based therapies, particularly mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells, and embryonic or induced pluripotent stem cells all offer considerable promise for ARDS. Of these cell types, mesenchymal stromal cells offer the greatest potential for allogeneic therapy, given the large body of preclinical data supporting their use, and the advanced state of our understanding of their diverse mechanisms of action. Although other stem cells such as EPCs also have therapeutic potential, greater barriers exist, particularly the requirement for autologous EPC therapy. Other stem cells, such as ESCs and iPSCs, are at an earlier stage in the translational process, but offer the hope of directly replacing injured lung tissue. Ultimately, lung-derived stem cells may offer the greatest hope for lung diseases, given their homeostatic role in replacing and repairing damaged native lung tissues. MSCs are currently in early phase clinical trials, the results of which will be of critical importance to subsequent translational efforts for MSCs in ARDS. A number of translational challenges exist, including minimizing variability in cell batches, developing standard tests for cell potency, and producing large amounts of clinical-grade cells for use in patients. Summary: Cell-based therapies, particularly MSCs, offer considerable promise for the treatment of ARDS. Overcoming translational challenges will be important to fully realizing their therapeutic potential for ARDS.

Purpose of review: Although results from clinical trials have advanced the treatment of acute respiratory distress syndrome (ARDS), mortality remains high. More recently, focus has shifted from treatment of ARDS to early identification and prevention in at-risk populations. Recent findings: There have been 30 published and registered clinical trials with either the primary or secondary goal of reducing ARDS. Summary: With this change in paradigm, come additional challenges and consideration in study design that depends not only on the intervention but also whether the intervention aims for a primary, secondary, or tertiary prevention of ARDS that targets a patient population for universal, selective, or indicated prevention. These epidemiologic concepts of prevention in public health also apply to ARDS and are relevant to the study population to target, the timing of the intervention relative to critical illness, the study design and outcomes to measure in an ARDS prevention study. This shift in focus is reflected by the new National Heart Lung Blood Institute Prevention and Early Treatment of Acute Lung Injury network, and signifies an overall movement away from reacting to and supporting acute organ failure after it is established to early detection and prevention in acute critical illness wherever and whenever it may occur.

Purpose of review: Circulatory failure is a frequent complication during acute respiratory distress syndrome (ARDS) and is associated with a poor outcome. This review aims at clarifying the mechanisms of circulatory failure during ARDS. Recent findings: For the past decades, the right ventricle (RV) has gained a crucial interest since many authors confirmed the high incidence of acute cor pulmonale during ARDS and showed a potential role of the acute cor pulmonale in the poor outcome of ARDS patients. The most important recent progress demonstrated in ARDS ventilatory strategy is represented by the prone position, which has a huge beneficial effect on RV afterload. This review will focus on the mechanisms responsible for the RV dysfunction/failure during ARDS and on the strategy, which allows improving the right ventricular function. Summary: The RV has a pivotal role in the circulatory failure of ARDS patients. The ventilatory strategy during ARDS has to pay a peculiar attention to the RV to rigorously control its afterload.

Purpose of review: The objective of this article is to review the most recent literature regarding the management of acute hypercapnic respiratory failure (AHRF). Recent findings: In the field of AHRF management, noninvasive ventilation (NIV) has become the standard method of providing primary mechanical ventilator support. Recently, extracorporeal carbon dioxide removal (ECCO2R) devices have been proposed as new therapeutic option. Summary: NIV is an effective strategy in specific settings and in selected population with AHRF. To date, evidence on ECCO2R is based only on case reports and case-control trials. Although the preliminary results using ECCO2R to decrease the rate of NIV failure and to wean hypercapnic patients from invasive ventilation are remarkable; further randomized studies are needed to assess the effects of this technique on both short-term and long-term clinical outcomes.

Purpose of review: The purpose of the review is to alert clinicians to the prevalent and frequently underrecognized problem of asynchrony in mechanically ventilated patients. To provide a mechanistic model of patient-ventilator asynchrony to help personnel understand how different asynchronies develop. To provide practical advice on how to recognize and solve different asynchronies in different contexts. Recent findings: Patient-ventilator asynchrony is a serious problem that is associated with prolonged mechanical ventilation, prolonged ICU and hospital stays, and increased mortality. Asynchronies can occur in all modes of invasive and noninvasive ventilation in all care contexts. Summary: The review provides insights into the causes of patient-ventilator asynchrony and mechanisms involved in the development of specific types of asynchrony. It explores the effects of sedation on the development of asynchrony and the impact of new ventilator modes. It also discusses the prevalence of asynchrony and its effects on outcome.