Gajic, Ognjen

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 F io 2 (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.

Objective: The Lung Injury Prediction Score identifies patients at risk for acute respiratory distress syndrome in the emergency department, but it has not been validated in non-emergency department hospitalized patients. We aimed to evaluate whether Lung Injury Prediction Score identifies non-emergency department hospitalized patients at risk of developing acute respiratory distress syndrome at the time of critical care contact. Design: Retrospective study. Setting: Five academic medical centers. Patients: Nine hundred consecutive patients (≥ 18 yr old) with at least one acute respiratory distress syndrome risk factor at the time of critical care contact. Interventions: None. Measurements and Main Results: Lung Injury Prediction Score was calculated using the worst values within the 12 hours before initial critical care contact. Patients with acute respiratory distress syndrome at the time of initial contact were excluded. Acute respiratory distress syndrome developed in 124 patients (13.7%) a median of 2 days (interquartile range, 2–3) after critical care contact. Hospital mortality was 22% and was significantly higher in acute respiratory distress syndrome than non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001). Increasing Lung Injury Prediction Score was significantly associated with development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI, 1.21–1.42) and the composite outcome of acute respiratory distress syndrome or death (odds ratio, 1.26; 95% CI, 1.18–1.34). A Lung Injury Prediction Score greater than or equal to 4 was associated with the development of acute respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26–7.72), composite outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95% CI, 1.68–3.49), and acute respiratory distress syndrome after accounting for the competing risk of death (hazard ratio, 3.71; 95% CI, 2.05–6.72). For acute respiratory distress syndrome development, the Lung Injury Prediction Score has an area under the receiver operating characteristic curve of 0.70 and a Lung Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses only 10% of acute respiratory distress syndrome cases), 31% specificity, 17% positive predictive value, and 95% negative predictive value. Conclusions: In a cohort of non-emergency department hospitalized patients, the Lung Injury Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can identify patients at increased risk of acute respiratory distress syndrome and/or death at the time of critical care contact but it does not perform as well as in the original emergency department cohort.

Objectives: Approximately half of ICU admissions are comprised of patients older than 65 years old. Mild cognitive impairment is a common disorder affecting 10–20% of patients in the same age group. A need exists for exploring mild cognitive impairment and risk of critical illness. As mild cognitive impairment may be a contributor to poorer overall health or be a result of it, we sought to determine whether the presence of mild cognitive impairment independently increases the risk of critical illness admissions. Design: Data from the Mayo Clinic Study of Aging were analyzed. All study participants underwent prospective comprehensive cognitive testing and expert panel consensus diagnosis of both cognitive function and clinical state at baseline and subsequent visits. Comparisons were made between those with normal cognitive function and mild cognitive impairment regarding baseline health and frequency of critical illness. Setting: Single-center population-based cohort out of Olmsted County, MN. Participants: All individuals 70–89 years old were screened for prospective enrollment in the Mayo Clinic Study of Aging. Patients with preexisting dementia and ICU admission within 3 years of entry to the study were excluded from this analysis. Interventions: None. Measurements and Main Results: Of 2,425 patients analyzed from the Mayo Clinic Study of Aging, 1,734 patients (71%) were included in the current study. Clinical factors associated with baseline mild cognitive impairment included age, male gender, stroke, and poorer health self-rating. Using a Cox regression model adjusting for these and a priori variables of baseline health, the presence of mild cognitive impairment remained a significant predictor of ICU admission (hazard ratio, 1.50 [1.15–1.96]; p = 0.003). Conclusions and Relevance: The presence of mild cognitive impairment is independently associated with increased critical illness admission. Further prospective studies are needed to analyze the impact of critical illness on cognitive function.

Introduction Acute respiratory failure (ARF) often presents and progresses outside of the intensive care unit. However, recognition and treatment of acute critical illness is often delayed with inconsistent adherence to evidence-based care known to decrease the duration of mechanical ventilation (MV) and complications of critical illness. The goal of this trial is to determine whether the implementation of an electronic medical record-based early alert for progressive respiratory failure coupled with a checklist to promote early compliance to best practice in respiratory failure can improve the outcomes of patients at risk for prolonged respiratory failure and death. Methods and analysis A pragmatic stepped-wedged cluster clinical trial involving 6 hospitals is planned. The study will include adult hospitalised patients identified as high risk for MV >48 hours or death because they were mechanically ventilated outside of the operating room or they were identified as high risk for ARF on the Accurate Prediction of PROlonged VEntilation (APPROVE) score. Patients with advanced directives limiting intubation will be excluded. The intervention will consist of (1) automated identification and notification of clinician of high-risk patients by APPROVE or by invasive MV and (2) checklist of evidence-based practices in ARF (Prevention of Organ Failure Checklist—PROOFCheck). APPROVE and PROOFCheck will be developed in the pretrial period. Primary outcome is hospital mortality. Secondary outcomes include length of stay, ventilator and organ failure-free days and 6-month and 12-month mortality. Predefined subgroup analysis of patients with limitation of aggressive care after study entry is planned. Generalised estimating equations will be used to compare patients in the intervention phase with the control phase, adjusting for clustering within hospitals and time. Ethics and dissemination The study was approved by the institutional review boards. Results will be published in peer-reviewed journals and presented at international meetings. Trial registration number NCT02488174.

Abstract Rationale The management of severe and refractory hypoxemia in critically ill adult patients is practice based. Variability across individual practitioners and institutions is not well documented. Objectives To conduct a nationwide survey of critical care physicians in the United States regarding accepted definitions and management strategies for severe and refractory hypoxemia. Methods A web-based survey was distributed to a stratified random sample of adult intensivists listed in the American Medical Association Physician Masterfile. The survey was generated by using a mixed-methods approach. Measurements and Main Results: In the survey, 4,865 e-mails were sent and 791 (16.3%) were opened. Among those who opened the e-mail message, 50% (n = 396) responded, representing 8.1% of total surveys sent. Seventy-two percent stated that their institutions lacked a protocol for identification and management of severe or refractory hypoxemia in the setting of acute respiratory failure. While the majority of respondents used low-Vt ventilation (81%), high positive end-expiratory pressure (86%), recruitment maneuvers (89%), and either bolus or infusion neuromuscular blockade (94%), there was marked variability in the use of specific rescue strategies as tier 1 or 2 interventions: prone position (27.8% vs. 47.8%, respectively), extracorporeal membrane oxygenation (2.3% vs. 51.2%, respectively), airway pressure release ventilation (49% vs. 34.5%, respectively), inhaled vasodilators (30.1% vs. 40%, respectively), and high-frequency oscillatory ventilation (7.8% vs. 40%, respectively). The variability was partly explained by providers’ expertise with particular rescue strategies (77.7%), advance directives (70.1%), the training of allied health staff (62.3%), and institutional availability (53.8%). Conclusions U.S. adult critical care physicians predominantly employ lung-protective ventilation for severe hypoxemia. A wide variation in other rescue strategies is noted, which is partly explained by user expertise and availability. Less than 30% institutions have formal protocols for management of refractory hypoxemia.

Abstract Rationale Respiratory failure represents a major risk for morbidity and mortality. Although generally managed in the intensive care unit (ICU), respiratory failure often begins elsewhere. Checklists of care processes to minimize the duration of mechanical ventilation and adverse events are routinely used in the ICU, but are uncommonly used outside the ICU. Objectives To develop consensus among a multidisciplinary expert panel on care practices to include in a checklist of best practices for critically ill patients with respiratory failure before and after ICU admission. Methods A multidisciplinary expert panel was assembled. The panel was tasked with creating a checklist of care processes aimed at decreasing progression to respiratory failure, duration of mechanical ventilation, mortality in mechanical ventilation, and adverse events. Over the course of multiple teleconferences and e-mail communications, the Prevention of Organ Failure Checklist list was reviewed, refined, and voted upon. Items that received greater than 75% of the vote were included in the final checklist. Measurements and Main Results: Using a modified Delphi process, the expert panel was able to compile Prevention of Organ Failure Checklist into 20 items that aimed to decrease mechanical ventilation by assessing the causes of acute respiratory failure, ventilation strategies, sedation, and general critical care processes, as well as to avoid unwanted or nonbeneficial interventions. Conclusions The modified Delphi process identified readily available preventative interventions suitable for checklist implementation in patients with or progressing to respiratory failure even before ICU admission.

Objectives: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. Design: Retrospective cohort study. Setting: Mayo Clinic, Rochester, MN. Patients: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. Interventions: None. Measurements and Main Results: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell transplantation (5.0%). Acute respiratory distress syndrome developed in 75 patients (15.6%) undergoing allogeneic hematopoietic stem cell transplantation and 58 patients (2.7%) undergoing autologous hematopoietic stem cell transplantation. Median time to acute respiratory distress syndrome development was 55.4 days (interquartile range, 15.1–139 d) in allogeneic hematopoietic stem cell transplantation and 14.2 days (interquartile range, 10.5–124 d) in autologous hematopoietic stem cell transplantation. Twenty-eight-day mortality was 46.6%. At 12 months following hematopoietic stem cell transplantation, 89 patients (66.9%) who developed acute respiratory distress syndrome had died. Only 7 of 133 acute respiratory distress syndrome cases met criteria for engraftment syndrome and 15 for diffuse alveolar hemorrhage. Conclusions: Acute respiratory distress syndrome is a frequent complication following hematopoietic stem cell transplantation, dramatically influencing patient-important outcomes. Most cases of acute respiratory distress syndrome following hematopoietic stem cell transplantation do not meet criteria for a more specific post-transplantation pulmonary syndrome. These findings highlight the need to better understand the risk factors underlying acute respiratory distress syndrome in this population, thereby facilitating the development of effective prevention strategies.