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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.

BACKGROUND: Subjects with severe hypoxemic respiratory failure have shown a high mortality in previous studies. METHODS: All adult ICU patients requiring mechanical ventilation from 2005 to 2010 at Mayo Clinic were screened for severe hypoxemia (Murray lung injury score of ≥ 3). Extracorporeal membrane oxygenation, prone positioning, high-frequency oscillatory ventilation (HFOV), and inhaled vasodilators were considered as rescue strategies. A propensity-based scoring was created for the indication or predilection to use each strategy. A model was created to evaluate the association of each rescue strategy with hospital mortality. RESULTS: Among 1,032 subjects with severe hypoxemia, 239 subjects received some form of rescue strategy (59 received a combination of therapies, and 180 received individual therapies). Inhaled vasodilators were the most common, followed by HFOV. Rescue strategies were used in younger subjects with severe oxygenation deficits. Subjects receiving rescue strategies had higher mortality and longer ICU stays. None of the strategies individually or in combination showed a significant association with hospital mortality after adjusting covariates by propensity scoring. Adjusted Odds ratios and respective 95% CI were as follows: HFOV 0.67 (0.35–1.27), extracorporeal membrane oxygenation 0.63 (0.18–1.92), prone position 1.07 (0.49–2.28), and inhaled vasodilators 1.17 (0.78–1.77). CONCLUSIONS: In this retrospective comparative effectiveness study, there was no association of rescue strategies with hospital mortality in subjects with severe hypoxemia.

Ventilator-associated events (VAEs) are associated with increased risk of poor outcomes, including death. Bundle practices including thromboembolism prophylaxis, stress ulcer prophylaxis, oral care, and daily sedation breaks and spontaneous breathing trials aim to reduce rates of VAEs and are endorsed as quality metrics in the intensive care units. We sought to create electronic search algorithms (digital signatures) to evaluate compliance with ventilator bundle components as the first step in a larger project evaluating the ventilator bundle effect on VAE. We developed digital signatures of bundle compliance using a retrospective cohort of 542 ICU patients from 2010 for derivation and validation and testing of signature accuracy from a cohort of random 100 patients from 2012. Accuracy was evaluated against manual chart review. Overall, digital signatures performed well, with median sensitivity of 100% (range, 94.4%–100%) and median specificity of 100% (range, 100%–99.8%). Automated ascertainment from electronic medical records accurately assesses ventilator bundle compliance and can be used for quality reporting and research in VAE.