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Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS).Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions.Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7).Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772). [ABSTRACT FROM AUTHOR]

Introduction: Methylene blue (MB) infusion is frequently used to localize the parathyroid glands during parathyroidectomy and generally considered safe. Several recent reports suggest neurological toxicity and post-operative altered mental state typically after large dose infusions. The mechanism by which MB has neurotoxic effects in some patients remains uncertain.Methods/results: Case Report: A 67-year-old male underwent lumbar laminectomy followed by parathyroidectomy. Postoperatively, he was comatose (Glasgow Coma Scale of 7) and underwent extensive neurological evaluation. Brain computed tomography (CT) imaging and CT angiography revealed no ischemia, vessel occlusion, or hemorrhage. Electroencephalogram (EEG) showed only slowing of cerebral hemispheric activity bilaterally. Over the next 48 h, his mental status slowly improved and the patient made a full neurological recovery (Glasgow Coma Scale 15).Conclusion: Methylene blue, when used in patients on antidepressant drugs, may be associated with a transient encephalopathic state and serotonin syndrome. Patients on antidepressants undergoing parathyroidectomy who may receive MB infusion should be considered for alternative parathyroid gland identification or discontinuation of the antidepressants before surgery. MB-associated serotonin syndrome is an increasing and under recognized ('green') post-operative encephalopathy that warrants education to critical care neurologists and other physicians. [ABSTRACT FROM AUTHOR]

Objective: To investigate the hypothesis that tissue changes induced by invasive thoracic procedures may be associated with increased fluorine 18-labeled fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scans, potentially leading to these tissue changes being mistaken for malignancies. Patients and Methods: We retrospectively reviewed the records of all patients undergoing bronchoscopies and FDG-PET at Mayo Clinic Jacksonville from February 2002 to September 2004 and identified patients who had undergone computed tomography (CT) of the chest and bronchoscopy before FDG-PET. We identified and reviewed the imaging studies of patients who had increased FDG uptake on PET scans and whose CT scans showed no corresponding abnormalities suggestive of malignancy. Results: Eighty-one patients had undergone both bronchoscopy and PET within the defined study period. Of these, 45 (56%) underwent PET within 4 weeks after bronchoscopy, and 13 (29%) of these 45 patients had increased FDG uptake on PET scans that did not correlate with pathological findings on CT. We judged that increased uptake on 3 (23%) of the 13 PET scans was most likely related to the bronchoscopic procedure. Additionally, 2 patients who had undergone thoracoscopy after bronchoscopy but before PET had discordant CT and PET findings. Conclusion: Invasive thoracic procedures may cause an increased uptake of radiotracer on PET scans that could be mistakenly interpreted as evidence of malignancy. To avoid clinical misjudgment, clinicians should perform PET before invasive thoracic procedures. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia is still a major cause of morbidity and mortality worldwide. Since the inflammatory response induced by the immune system is often a major contributor to the lung injury, it becomes reasonable to assess the potential benefit of anti-inflammatory agents in treating community-acquired pneumonia. The role of corticosteroids as adjunct anti-inflammatory agents in treating community-acquired pneumonia is still controversial. Several studies have assessed the benefit of their use in patients with community-acquired pneumonia. In most of those studies, the route of corticosteroids administration was systemic. The aim of this article is to provide a concise review of the role of corticosteroids in treating community-acquired pneumonia when administered via inhalational route, with the potential benefit of avoiding systemic side effects of corticosteroids while exerting the same anti-inflammatory effects on the lungs. Conclusion: the use of inhaled corticosteroids may be of benefit in certain patient subsets with community-acquired pneumonia. Further randomized controlled trials are needed for better determination of such patient subsets.

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).

In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTubeTM between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (ViberTM), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.

Objective: To study the association between ventilatory function and cognitive and behavioral impairment in ALS patients accounting for the effects of pertinent covariates. Methods : Four hundred and eighty-one patients were identified from the Mayo Clinic Florida ALS registry who had concurrent forced vital capacity (FVC) and cognitive and behavioral testing using the ALS Cognitive Behavioral Screen (ALS-CBS). Multiple linear regression analysis was used to study the effects of FVC and relevant covariates on the ALS-CBS cognition score, subscores, and caregiver behavioral inventory. Results : FVC was positively correlated to the cognitive and behavioral subscores on the ALS-CBS ( p  < 0.001), and the correlation was independent of the effects of site of ALS onset, age, and years of education. Conclusion : Cognitive and behavioral function may be adversely affected by ventilatory impairment in ALS. The presence of cognitive and behavioral impairment warrants a detailed assessment of ventilatory function.

Study Objectives: The objectives of this study were to assess the effect of obstructive sleep apnea (OSA) on the risk of acute pulmonary embolism (PE), hospital outcomes including mortality, and PE recurrence., Methods: We retrospectively enrolled adult patients, admitted to Mayo Clinic Hospital in Rochester, Minnesota, within a 5-year period (2009-2013). We compared frequency of PE, hospital mortality, and secondary outcomes in patients with OSA versus patients without OSA. We assessed risk of PE recurrence in relation to compliance with OSA therapy., Results: Of 25,038 patients, 3,184 (13%) had OSA and 283 (1.1%) experienced PE. Frequency of PE in patients with and without OSA was 2.4% versus 0.9% (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.9-3.3; P < .001). OSA was independently associated with increased risk of PE after adjusting for demographics and comorbidities (OR, 1.44; 95% CI, 1.07-1.9; P = .017). Adjusted hospital mortality was increased in patients with PE (OR, 2.88; 95% CI, 1.7-4.9; P < .001) but not in patients with OSA (OR, 0.98; 95% CI, 0.7-1.4, P = .92). OSA was not a significant determining factor for mortality in patients who experienced a PE (OR, 0.56; 95% CI, 0.1.1-2.78; P = .47), adjusting for demographics, PE severity, and Charlson comorbidity index. Adjusted risk of PE recurrence was greater in patients with OSA compared with patients without OSA (OR, 2.21; 95% CI, 1.05-4.68; P < .04). The patients compliant with OSA therapy had a lower rate of PE recurrence (16% vs 32%; P = not significant)., Conclusions: Although OSA significantly increases risk of acute PE occurrence and recurrences, related hospital mortality was not greater in patients with OSA compared with those without OSA. OSA therapy might have a modifying effect on PE recurrence., (© 2020 American Academy of Sleep Medicine.)

Background: Hypotension is a frequent complication in the intensive care unit (ICU) after adult cardiac surgery., Aim: To describe frequency of hypotension in the ICU following adult cardiac surgery and its relation to the hospital outcomes., Methods: A retrospective study of post-cardiac adult surgical patients at a tertiary academic medical center in a two-year period. We abstracted baseline demographics, comorbidities, and all pertinent clinical variables. The primary predictor variable was the development of hypotension within the first 30 min upon arrival to the ICU from the operating room (OR). The primary outcome was hospital mortality, and other outcomes included duration of mechanical ventilation (MV) in hours, and ICU and hospital length of stay in days., Results: Of 417 patients, more than half (54%) experienced hypotension within 30 min upon arrival to the ICU. Presence of OR hypotension immediately prior to ICU transfer was significantly associated with ICU hypotension (odds ratio = 1.9; 95% confidence interval: 1.21-2.98; P < 0.006). ICU hypotensive patients had longer MV, 5 (interquartile ranges 3, 15) vs 4 h (interquartile ranges 3, 6), P = 0.012. The patients who received vasopressor boluses ( n = 212) were more likely to experience ICU drop-off hypotension (odds ratio = 1.45, 95% confidence interval: 0.98-2.13; P = 0.062), and they experienced longer MV, ICU and hospital length of stay ( P < 0.001, for all)., Conclusion: Hypotension upon anesthesia-to-ICU drop-off is more frequent than previously reported and may be associated with adverse clinical outcomes., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The aim is to provide a narrative review of the role of corticosteroids, with and without inhaled beta agonist, in communityacquired pneumonia. Community and health-care associated pneumonia remain leading causes of morbidity and mortality despite appropriate antibiotic therapy. The pneumonia-associated adverse outcomes are not only related to the infectious organism, but also to a dysfunctional host-immune response resulting in overwhelming inflammation. Use of systemic corticosteroids as adjuvant therapy in pneumonia remains controversial. Multiple randomized clinical trials evaluating corticosteroids in patients with community acquired pneumonia have found discrepant results in terms of benefits and adverse effects. Inhaled delivery of corticosteroids offer the potential advantage of providing therapeutic benefits directly to the lung, with minimal to no adverse systemic effects. CONCLUSION: Although meta-analyses suggest potential benefits in a select group of patients with more severe pneumonia, the ideal timing, dose, route of delivery, duration, and patient selection remain to be established. A smaller body of literature suggests benefit of inhaled corticosteroids, with or without inhaled beta agonists, but future large scale clinical trials are needed to establish clinical benefit with inhaled delivery., (Copyright © 2020 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Background: Limited critical care subspecialty training and experience is available in many low- and middle-income countries, creating barriers to the delivery of evidence-based critical care. We hypothesized that a structured tele-education critical care program using case-based learning and ICU management principles is an efficient method for knowledge translation and quality improvement in this setting., Methods and Interventions: Weekly 45-min case-based tele-education rounds were conducted in the recently established medical intensive care unit (MICU) in Banja Luka, Bosnia and Herzegovina. The Checklist for Early Recognition and Treatment of Acute Illness (CERTAIN) was used as a platform for structured evaluation of critically ill cases. Two practicing US intensivists fluent in the local language served as preceptors using a secure two-way video communication platform. Intensive care unit structure, processes, and outcomes were evaluated before and after the introduction of the tele-education intervention., Results: Patient demographics and acuity were similar before (2015) and 2 years after (2016 and 2017) the intervention. Sixteen providers (10 physicians, 4 nurses, and 2 physical therapists) evaluated changes in the ICU structure and processes after the intervention. Structural changes prompted by the intervention included standardized admission and rounding practices, incorporation of a pharmacist and physical therapist into the interprofessional ICU team, development of ICU antibiogram and hand hygiene programs, and ready access to point of care ultrasound. Process changes included daily sedation interruption, protocolized mechanical ventilation management and liberation, documentation of daily fluid balance with restrictive fluid and transfusion strategies, daily device assessment, and increased family presence and participation in care decisions. Less effective (dopamine, thiopental, aminophylline) or expensive (low molecular weight heparin, proton pump inhibitor) medications were replaced with more effective (norepinephrine, propofol) or cheaper (unfractionated heparin, H2 blocker) alternatives. The intervention was associated with reduction in ICU (43% vs 27%) and hospital (51% vs 44%) mortality, length of stay (8.3 vs 3.6 days), cost savings ($400,000 over 2 years), and a high level of staff satisfaction and engagement with the tele-education program., Conclusions: Weekly, structured case-based tele-education offers an attractive option for knowledge translation and quality improvement in the emerging ICUs in low- and middle-income countries.

Study Objectives: Overnight pulse oximetry (OPO) is commonly used as a screening test for obstructive sleep apnea. Heart rate variability (HRV) correlates well with apnea-hypopnea index during polysomnography (PSG). We hypothesized that visual correlation of episodic increase in HRV with minimal oxygen desaturations on normal OPO (oxygen desaturation index less than 5 events/h) is predictive of OSA., Methods: A retrospective analysis of patients undergoing OPO and PSG in 1 year was performed. We included only OPO performed on room air and interpreted as normal. Visual correlation between simultaneous increase in HRV and minimal oxygen desaturation was independently assessed by three raters, resulting in the consensus agreement. The primary outcome was presence of OSA on the subsequent PSG., Results: Of 936 patients with OPO and PSG, 109 patients had normal overnight oximetry study on room air. Of these, 65 (60%) were females, median (interquartile range) age was 54 years (44, 67), body mass index was 29 kg/m 2 (25, 32), and the median oxygen desaturation index was 1.8 events/h (1, 2.7). Consensus agreement identified 54 patients with visual correlation between pulse and minimal oxygen desaturations. Thirty-two patients (29%) were found to have OSA on PSG, of which 24 (75%) could have been accurately predicted by the consensus agreement (odds ratio 4.70, 95% confidence interval 1.87-11.8, P < .001). When adjusted for pertinent clinical and demographic variables, consensus agreement was independently associated with diagnosis of OSA on subsequent PSG (odds ratio 5.6, 95% confidence interval 1.76-20.9, P = .003)., Conclusions: Visual correlation between episodic increase in HRV and minimal oxygen desaturations on OPO is an independent predictor of OSA, and promising marker for clinical use., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: To evaluate clinical recognition of sleep apnea and related outcomes in patients hospitalized with acute ischemic stroke., Methods: A retrospective study of all patients hospitalized with acute ischemic stroke from April 2008 to December 2014. The primary predictor and outcome variables were sleep apnea and hospital mortality, respectively. Secondary outcomes were mechanical ventilation, hospital length of stay, and the survivor's functional level by the modified Rankin scale. A sensitivity multivariate regression analysis included the propensity score for cardiovascular comorbidities and sleep apnea., Results: Of 989 patients, 190 (19%) were considered to have sleep apnea. Only 42 patients (22%) received any treatment for sleep apnea during the hospital stay. Despite higher prevalence of cardiovascular comorbidities, the patients with sleep apnea had lower hospital mortality, 1% versus 5.6% in patients without sleep apnea (odds ratio [OR] 0.18; 95% confidence interval [CI], 0.03-0.58, P = .002). Only the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow coma scale (GCS) were significant predictors of adjusted hospital mortality (OR 1.06, 95% CI 1.01-1.11, P = .01 and OR 0.61, 95% CI 0.51-0.69, P ≤ .001, respectively). A composite clinical propensity score for sleep apnea and cardiovascular comorbidities was significantly associated with decreased mortality, independent to either NIHSS (OR 0.11, 95% CI 0.017-0.71; P = .02) or GCS (OR 0.07, 95% CI 0.01-0.52; P = .01)., Conclusions: Prevalence of sleep apnea in our study was low, likely because of clinical underrecognition. Despite having more cardiovascular disease, the patients with acute stroke and sleep apnea had less severe neurological injury and lower unadjusted mortality than those without a history of sleep apnea., (© 2018 American Academy of Sleep Medicine)

Background: We assessed the potential of risk stratification of ARDS patients using SpO 2 /FiO 2 and positive end-expiratory pressure (PEEP) at ARDS onset and after 24 h., Methods: We used data from a prospective observational study in patients admitted to a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Risk stratification was by cutoffs for SpO 2 /FiO 2 and PEEP. The primary outcome was in-hospital mortality. Patients with moderate or severe ARDS with a length of stay of > 24 h were included in this study. Patients were assigned to four predefined risk groups: group I (SpO 2 /FiO 2  ≥ 190 and PEEP < 10 cm H 2 O), group II (SpO 2 /FiO 2  ≥ 190 and PEEP ≥ 10 cm), group III (SpO 2 /FiO 2  < 190 and PEEP < 10 cm H 2 O) and group IV (SpO 2 /FiO 2  < 190 and PEEP ≥ 10 cm H 2 O)., Results: The analysis included 456 patients. SpO 2 /FiO 2 and PaO 2 /FiO 2 had a strong relationship (P < 0.001, R 2  = 0.676) that could be described in a linear regression equation (SpO 2 /FiO 2  = 42.6 + 1.0 * PaO 2 /FiO 2 ). Risk stratification at initial ARDS diagnosis resulted in groups that had no differences in in-hospital mortality. Risk stratification at 24 h resulted in groups with increasing mortality rates. The association between group assignment at 24 h and outcome was confounded by several factors, including APACHE IV scores, arterial pH and plasma lactate levels, and vasopressor therapy., Conclusions: In this cohort of patients with moderate or severe ARDS, SpO 2 /FiO 2 and PaO 2 /FiO 2 have a strong linear relationship. In contrast to risk stratification at initial ARDS diagnosis, risk stratification using SpO 2 /FiO 2 and PEEP after 24 h resulted in groups with worsening outcomes. Risk stratification using SpO 2 /FiO 2 and PEEP could be practical, especially in resource-limited settings.

Background: Cardiac arrest survivors may have disabilities due to hypoxic brain injury. Patients with obstructive sleep apnea are exposed to intermittent hypoxemia that may lead to ischemic preconditioning. We have hypothesized that patients with obstructive sleep apnea have better neurological outcomes following a cardiac arrest due to preconditioning of the brain., Methods: We retrospectively analyzed all the survivors of in-hospital cardiac arrest from January 2006 to September 2016. Patients with confirmed or suspected obstructive sleep apnea were selected for further analysis and those without were used as comparison. Primary outcome was neurological functionality on hospital discharge by the Cerebral Performance Category., Results: A total of 739 patients had cardiac arrest within the study period. The immediate mortality rate was 59% (N=43) in patients with obstructive sleep apnea and 94% (N=623) in those without (p<0.001). Approximately 10% (N=73) were discharged alive and these were selected for further analysis. Patients without obstructive sleep apnea had more frequently "Poor" outcomes compared to those with obstructive sleep apnea (OR 2.91; 95% CI, 1.11-7.66; p=0.03). After adjusting in a multivariate analysis, obstructive sleep apnea was "protective" of "Poor" neurological outcomes: adjusted OR 0.21; 95% CI, 0.06-0.64; p=0.01., Conclusion: Patients with obstructive sleep apnea had better unadjusted survival rates, and favorable adjusted neurological outcomes at discharge compared to those without obstructive sleep apnea. These results suggest that obstructive sleep apnea patients may tolerate better acute brain ischemia due to preconditioning., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The Surviving Sepsis Campaign guidelines are designed to decrease mortality through consistent application of a 7-element bundle. This study evaluated the impact of improvement in bundle adherence using a time-series analysis of compliance with the bundle elements before and after interventions intended to improve the process, while also looking at hospital mortality. This article describes interventions used to improve bundle compliance and hospital mortality in patients admitted through the emergency department with sepsis, severe sepsis, or septic shock. Quality improvement methodology was used to develop high-impact interventions that led to dramatically improved adherence to the Surviving Sepsis Campaign guidelines bundle. Improved performance was associated with a significant decrease in the in-hospital mortality of severe sepsis patients presenting to the emergency department.

Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance., Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome., Setting: Five academic centers in the United States., Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome., Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days., Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%)., Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

Background: Sepsis is a major reason for intensive care unit (ICU) admission, also in resource-poor settings. ICUs in low- and middle-income countries (LMICs) face many challenges that could affect patient outcome., Aim: To describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU., Findings: Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources., Conclusions: Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both at a macro- and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

Importance: Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear., Objective: To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS., Design, Setting, and Participants: A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score ≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort., Interventions: Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death., Main Outcomes and Measures: The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final α level of .0737 (α = .10 overall) was required for statistical significance of the primary outcome., Results: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, -0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13)., Results: Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text], Conclusions and Relevance: Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial., Trial Registration: clinicaltrials.gov Identifier: NCT01504867.

Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality., Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers' web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies' bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic., Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35-1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39-2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia -case-fatality: RR 0.91; 95% CI 0.52-1.59, p = 0.74; and OR 0.72; 95% CI 0.59-0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85-1.05, p = 0.31; and OR 0.79; 95% CI 0.65-0.97, p = 0.02, respectively., Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.

Background: There is a need for improved clinical identification of hospitalized patients at risk of aspiration. We evaluated our novel phonetic test in a broad spectrum of patients at risk of aspiration in the ICU or intermediate care unit., Methods: We prospectively enrolled 60 hospitalized patients with aspiration risk, between December 2009 and September 2011, who subsequently underwent audio-recorded three-component phonetic bedside evaluation. The recordings were scored by two blinded speech-language pathologists. The institutional dysphagia admission screening test was performed by a bedside nurse. The primary outcomes, dysphagia and aspiration, were assessed by a videofluoroscopic swallowing study, fiber-optic endoscopic evaluation of swallowing, or both. We assessed the short- and long-term clinical outcomes (length of stay, subsequent aspiration pneumonia and respiratory failure, survival) and how these were associated with the phonetic and swallow assessments., Results: Statistically significant linear associations with dysphagia were noted for all three individual phonetic components. Also, there were statistically significant linear associations with aspiration for diadochokinesis (P = .050) and consensus auditory-perceptual evaluation of voice (P = .025). Diadochokinesis alone predicted dysphagia (area under the curve [AUC], 0.74; P = .001) and aspiration (AUC, 0.67; P = .012). Its predictive ability improved when combined with normalized dysphagia admission screening test results (AUC, 0.79; P = .001). The short- and long-term clinical outcomes were adversely affected by the worse phonetic/swallowing scores, although they were not statistically different., Conclusions: Abnormal phonation among ICU and intermediate care unit patients is associated with dysphagia and aspiration. Future investigative efforts should uncover the most effective combination of evaluations for accurate bedside detection of dysphagia and aspiration risk in a broad spectrum of patients., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The randomization process is expected to balance assignment between the groups, independent to the participant and/or investigator, and as such avoids systematic error. However, it is recognized that groups assigned through the randomization process are not completely the same. Generally, a table with baseline characteristics is provided, where investigators report demographic and pertinent clinical variables based on the random group assignment and P values for the each variable in attempt to either support the balanced assignment or to indicate that the balance between groups was not ideal. The recently published PROSEVA trial showed more than 50% relative risk reduction of 28-day mortality among ARDS patients in the prone group compared to the supine group. In order to demonstrate a novel approach and exemplify how imbalance in baseline characteristics between groups could have potentially contributed to the large observed effect, we pooled pertinent baseline clinical variables from the trial in a meta-analysis-like manner. In addition to the quantification, we assigned the variable's "quality" of probable effect on the outcome as likely beneficial or harmful. After pooling pertinent dichotomous variables by the probability of their effect on the outcome, it appeared that approximately 37% (18% to 60%) of the observed PROSEVA trial effect could have been due to differences in baseline clinical characteristics. The main limitation of this approach is that all variables are assumed to have similar weights on the outcome. Interestingly, the weights of beneficial and harmful effects on the outcome were very similar. The proposed method of assessment of potential imbalance between the intervention groups assesses not only the magnitude of the difference, but rather the pooled probability of beneficial or harmful effect towards outcome, as well. As such, it could be useful as a secondary measure for the assessment of imbalance in the trials with the unexpectedly large observed effects.

The development of acute respiratory distress syndrome (ARDS) carries significant risk of morbidity and mortality. To date, pharmacological therapy has been largely ineffective for patients with ARDS. We present our personal review aimed at outlining current and future directions for the pharmacological prevention of ARDS. Several available risk-stratification or prediction score strategies for identification of patients at risk of ARDS have been reported. Although not ready for clinical everyday use, they are and will be instrumental in the ongoing and future trials of pharmacoprevention of ARDS.Several systemic medications established the potential role in ARDS prevention based on the preclinical studies and observational data. Due to potential for systemic adverse effects to neutralize any pharmacological benefits of systemic therapy, inhaled medications appear particularly attractive candidates for ARDS prevention. This is because of their direct delivery to the site of proposed action (lungs), while the pulmonary epithelial surface is still functional.We postulate that overall morbidity and mortality rates from ARDS in the future will be contingent upon decreasing the overall incidence of ARDS through effective identification of those at risk and early application of proven supportive care and pharmacological interventions., (© The Author(s), 2015.)

Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO(2)/FiO(2)) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO(2)/FiO(2) measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS., Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO(2)/FiO(2). The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death., Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO(2)/FiO(2) values. Median SpO(2)/FiO(2) in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO(2)/FiO(2) and ARDS (P ≤ .001). The SpO(2)/FiO(2) was found to be an independent predictor of ARDS in a "dose-dependent" manner; for SpO(2)/FiO(2) < 100--odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO(2)/FiO(2) 100 < 200--OR 1.75 (1.16-2.58, P = .007), and for SpO(2)/FiO(2) 200 < 300--OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively., Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk., (© The Author(s) 2013.)

Purpose of Review: The paucity of effective therapeutic interventions in patients with the acute respiratory distress syndrome (ARDS) combined with overwhelming evidence on the importance of timely implementation of effective therapies to critically ill patients has resulted in a recent shift in ARDS research. Increasingly, efforts are being directed toward early identification of patients at risk with a goal of prevention and early treatment, prior to development of the fully established syndrome. The focus of the present review is on the prevention of ARDS in patients without this condition at the time of their healthcare encounter., Recent Findings: The primary thematic categories presented in the present review article include early identification of patients at risk of developing ARDS, optimization of care delivery and its impact on the incidence of ARDS, pharmacological prevention of ARDS, prevention of postoperative ARDS, and challenges and opportunities with ARDS prevention studies., Summary: Recent improvements in clinical care delivery have been associated with a decrease in the incidence of hospital-acquired ARDS. Despite the initial challenges, research in ARDS prevention has become increasingly feasible with several randomized controlled trials on ARDS prevention completed or on the way.

Inhaled corticosteroids are commonly prescribed for patients with severe chronic obstructive pulmonary disease. Although their use improves quality of life and reduces exacerbations, it is associated with increased risk of pneumonia. Curiously, their use has not been associated with increased risk of pneumonia-related or overall mortality. We review pertinent literature to further explore the effects of inhaled corticosteroids on incident pneumonia and mortality in patients with chronic obstructive pulmonary disease. The association of use of inhaled corticosteroids and incident pneumonia is substantial and has been present in the majority of the studies on the topic. This includes both randomized controlled trials and observational studies. However, all of the studies have substantial risk of bias. Most randomized trials are limited by lack of systematic ascertainment of pneumonia; they depended on adverse event reporting. Many observational studies included proper radiographic assessment of pneumonia, but they are limited by their retrospective, observational design. The unadjusted higher risk of pneumonia is associated with longer duration of use, more potent ICS compounds, and higher doses. That implies a dose-effect relationship. Unlike pneumonia, mortality is a precise outcome. Despite the robust association of inhaled corticosteroid use with increased risk of pneumonia, all studies find either no difference or a reduction in pulmonary-related and overall mortality associated with the use of inhaled corticosteroids. These observations suggest a double effect of inhaled corticosteroids (i.e., an adverse effect plus an unexplained mitigating effect).

Objectives: To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients., Methods: We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers' web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies., Results: Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57 to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87 to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients., Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies., (Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Objective: Inhaled corticosteroids and inhaled beta agonists were shown to decrease the lung injury in animal models. We investigated the association of pre-hospital use of inhaled corticosteroids and inhaled beta agonists with the incidence of Acute Respiratory Distress Syndrome (ARDS) in a population based cohort of hospitalized patients., Material and Methods: Retrospective cohort study of adult patients from Olmsted County, Minnesota admitted to the hospital with at least one predisposing condition for ARDS from 2001-2008. The association with pre-hospital use of inhaled corticosteroids and inhaled beta agonists was evaluated using univariate and multivariate analyses. Primary outcome was ARDS and secondary outcome was hospital mortality., Results: Out of 2429 hospitalized adult patients with at least one risk factor for ARDS, 10.5% of those taking and 14% of those not taking inhaled corticosteroids developed ARDS (OR 0.72; 0.53-0.97; p<0.03). Inhaled beta agonists showed similar unadjusted protective effect; 9.7% of users and 14.4% of non-users developed ARDS (OR 0.64; 0.48-0.86; p=0.003). After adjusting for risk factors, comorbidities and severity of illness in the multiple logistic regression model, use of inhaled beta agonists, but not inhaled corticosteroids, remained independently associated with decreased risk of ARDS (OR 0.48; 0.31-0.72; p<0.001 versus 0.87; 0.57-1.29; p=0.49). The estimated protective effects were more pronounced among patients with pneumonia compared to those without pneumonia., Conclusion: Prehospital use of inhaled beta agonists but not inhaled corticosteroids was significantly associated with decreased incidence of ARDS among hospitalized patients at risk, once adjusted for baseline characteristics, predisposing and comorbid conditions, as well as severity of illness., (Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.)

Objective: To investigate the impact of a sequence of educational interventions in a one-day course on focused transthoracic echocardiography (FOTE) by anesthesia and critical care practitioners., Design: A prospective analysis of the educational data., Setting: Educational setting in two academic medical centers and a medical meeting workshop organized by one of these institutions., Participants: Fifty-six anesthesia and critical care providers, divided into three groups, participated separately in a FOTE training course., Interventions: All participants received a sequence of educational intervention as follows: A standardized, multiple-choice pretest; a lecture on cardiac and lung ultrasound; and a FOTE "hands-on" training session. The same standardized test was administered and graded as a posttest., Measurements and Main Results: Fifty-six professionals attended the course in three separate groups: The first were cardiothoracic anesthesia fellows (n = 16) (group 1), the second included critical care practitioners (n = 21) (group 2), and the third were general anesthesiologists (n = 19) (group 3). Parasternal views were most difficult to obtain for all groups (58.1, 63.8, and 58%, respectively). The mean written test scores increased from 14.9±2 to 21.0±2.3 in group 1; from 12.3±3.8 to 19.2±3.7 in group 2; 12±3.5 to 21±2.4 in group 3, (p = 0.0003, 0.00005, 0.0001, respectively)., Conclusions: A FOTE training course improves image acquisition skills and knowledge to the same level independently of professional background and level of experience in critical care ultrasound., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited., Methods: This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center., Results: Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups., Conclusions: Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone.