Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members—A Multicenter, Multinational, Before-and-After Intervention Trial Objectives: To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members. Design: Prospective, before-and-after intervention evaluation. Setting: Two U.S. academic medical ICU’s, and one Italian academic medical/surgical ICU. Subjects: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. Interventions: A novel intervention titled “Family Care Rituals” during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay. Measurements and Main Results: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge. Conclusions: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients. This research was completed at following institutions: Rhode Island Hospital, Rush Medical Center, Azienda Ospedaliero-Universitaria Careggi. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The James M Cox Foundation provide support for this trial in the form of grant funding for study coordination, travel, supplies, and statistical analysis. Dr. Amass’s institution received funding from the National Heart, Lung, and Blood Institute (grant T32 HL134625), and he received support for article research from the National Institutes of Health. Drs. Amass’s, OMahoney’s, Caine’s, and Palmisciano’s institutions received funding from the James M. Cox Foundation. Dr. Villa received funding from Baxter and Pall. Dr. OMahoney received support for article research from the Family Foundation Grant. Ms. McFadden, Mr. Walsh, Ms. Caine, and Ms. Palmisciano received support for article research from James M. Cox Foundation. Dr. De Gaudio’s institution received funding from MSD Italia and Pall, and he received funding from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Timothy H. Amass, MD, ScM, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine. Department of Veterans Affairs, Eastern Colorado Health System. 1700 N. Wheeling Street, Office F2-266, Denver, CO 80045 E-mail: tim.amass@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Alive and Ventilator Free: A Hierarchical, Composite Outcome for Clinical Trials in the Acute Respiratory Distress Syndrome Objectives: Survival from acute respiratory distress syndrome is improving, and outcomes beyond mortality may be important for testing new treatments. The “ventilator-free days” score, is an established composite that equates ventilation on day 28 to death. A hierarchical outcome treating death as a worse than prolonged ventilation would enhance face validity, but performance characteristics and reporting of such an outcome are unknown. We therefore evaluated the performance of a novel hierarchical composite endpoint, the Alive and Ventilator Free score. Design: Using data from four Acute Respiratory Distress Syndrome Network clinical trials, we compared Alive and Ventilator Free to the ventilator-free days score. Alive and Ventilator Free compares each patient with every other patient in a win-lose-tie for each comparison. Duration of mechanical ventilation is only compared if both patients survived. We evaluated power of Alive and Ventilator Free versus ventilator-free days score under various circumstances. Setting: ICUs within the Acute Respiratory Distress Syndrome Network. Patients: Individuals enrolled in four Acute Respiratory Distress Syndrome Network trials. Interventions: None for this analysis. Measurements and Main Results: Within the four trials (n = 2,410 patients), Alive and Ventilator Free and ventilator-free days score had similar power, with Alive and Ventilator Free slightly more powerful when a mortality difference was present, and ventilator-free days score slightly more powerful with a difference in duration of mechanical ventilation. Alive and Ventilator Free less often found in favor of treatments that increased mortality and increased days free of ventilation among survivors. Conclusions: A hierarchical composite endpoint, Alive and Ventilator Free, preserves statistical power while improving face validity. Alive and Ventilator Free is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes. Approaches to interpretation of differences in Alive and Ventilator Free are also presented. Drs. Novack, Beitler, and Brown were involved in drafting the work. Drs. Yitshak-Sade, Thompson, Schoenfeld, Rubenfeld, and Talmor were involved in critical revision for important intellectual content. Drs. Novack, Beitler, Yitshak-Sade, and Brown were involved in statistical analysis. All authors were involved in substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. All authors were involved in final approval of the version to be published. All authors were involved in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the National Institutes of Health. Dr. Novack received funding from Cardiomed Consultants LLC. Drs. Beitler’s and Schoenfeld’s institution received funding from the National Institutes of Health (NIH). Drs. Beitler, Thompson, Schoenfeld, and Brown received support for article research from the NIH. Dr. Thompson’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) and Department of Defense; reports consulting for Bayer, Boehringer Ingelheim, and GlaxoSmithKline; and authorship for UpToDate, all outside the submitted work. Drs. Talmor (1UM1HL108724) and Beitler (K23HL133489) received funding from NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Samuel.Brown@imail.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Neuroprognostication Practices in Postcardiac Arrest Patients: An International Survey of Critical Care Providers Objectives: To characterize approaches to neurologic outcome prediction by practitioners who assess prognosis in unconscious cardiac arrest individuals, and assess compliance to available guidelines. Design: International cross-sectional study. Setting: We administered a web-based survey to members of Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology who manage unconscious cardiac arrest patients to characterize practitioner demographics and current neuroprognostic practice patterns. Subjects: Physicians that are members of aforementioned societies who care for successfully resuscitated cardiac arrest individuals. Interventions: Not applicable. Measurements and Main Results: A total of 762 physicians from 22 countries responses were obtained. A significant proportion of respondents used absent corneal reflexes (33.5%) and absent pupillary reflexes (36.2%) at 24 hours, which is earlier than the recommended 72 hours in the standard guidelines. Certain components of the neurologic examination may be overvalued, such as absent motor response or extensor posturing, which 87% of respondents considered being very or critically important prognostic indicators. Respondents continue to rely on myoclonic status epilepticus and neuroimaging, which were favored over median nerve somatosensory evoked potentials for prognostication, although the latter has been demonstrated to have a higher predictive value. Regarding definitive recommendations based on poor neurologic prognosis, most physicians seem to wait until the postarrest timepoints proposed by current guidelines, but up to 25% use premature time windows. Conclusions: Neuroprognostic approaches to hypoxic-ischemic encephalopathy vary among physicians and are often not consistent with current guidelines. The overall inconsistency in approaches and deviation from evidence-based recommendations are concerning in this disease state where mortality is so integrally related to outcome prediction. Drs. Maciel and Barden contributed equally for this article and shared first authorship. This study was conducted at Yale University School of Medicine. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Maciel received funding from Claude D. Pepper Older Americans Independence Center Junior Scholar award that supports preclinical studies of mechanisms of secondary brain injury in a rodent cardiac arrest model. Dr. Dhakar received funding from Adamas Pharmaceuticals and research support from Marinus Pharmaceuticals and UCB Biopharma for clinical trials. Dr. Greer’s institution received funding from National Institutes of Neurological Disorders and Stroke/National Institutes of Health, he received funding form medical-legal consultation, and he serves as Editor-in-Chief of Seminars in Neurology and has received compensation for medico-legal consultation. The remaining authors have disclosed that they do not have any potential conflicts of interest. ORCID 0000-0002-8763-5839 (to Dr. Maciel), ORCID 0000-0002-4901-4177 (to Dr. Barden), ORCID 0000-0002-7325-1148 (to Dr. Youn), ORCID 0000-0001-9275-2784 (to Dr. Dhakar), and ORCID 0000-0002-2026-8333 (to Dr. Gree). For information regarding this article, E-mail: carolina.maciel@neurology.ufl.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Effect of Best Practice Advisories on Sedation Protocol Compliance and Drug-Related Hazardous Condition Mitigation Among Critical Care Patients Objectives: To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions. Design: Retrospective observational cohort study. Setting: Two adult ICUs at two academic medical centers that share the same sedation protocol. Patients: Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol. Interventions: Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions. Measurements and Main Results: The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre–best practice advisory group; n = 694 in the post–best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6–60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45–3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9–47.1) absolute increase and a 74% (95% CI, 1.39–2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8–28.3) sooner than pre–best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses. Conclusions: Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Zullo is supported by award 5K12HS022998 from the Agency for Healthcare Research and Quality. He is supported, in part, by a research grant from Sanofi Pasteur to Brown University on unrelated work that aims to understand the epidemiology of infections in long-term care facilities. He is also supported by a Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship in Health Services Research and Development. Dr. Amass’ institution received funding from National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (grant number: T32HL134625), and the Brown University Respiratory Research Training Program, and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: rgreene1@lifespan.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Formyl Peptide Receptor-1 Blockade Prevents Receptor Regulation by Mitochondrial Danger-Associated Molecular Patterns and Preserves Neutrophil Function After Trauma Objectives: Trauma predisposes to systemic sterile inflammation (systemic inflammatory response syndrome) as well as infection, but the mechanisms linking injury to infection are poorly understood. Mitochondrial debris contains formyl peptides. These bind formyl peptide receptor-1, trafficking neutrophils to wounds, initiating systemic inflammatory response syndrome, and wound healing. Bacterial formyl peptides, however, also attract neutrophils via formyl peptide receptor-1. Thus, mitochondrial formyl peptides might suppress neutrophils antimicrobial function. Also, formyl peptide receptor-1 blockade used to mitigate systemic inflammatory response syndrome might predispose to sepsis. We examined how mitochondrial formyl peptides impact neutrophils functions contributing to antimicrobial responses and how formyl peptide receptor-1 antagonists affect those functions. Design: Prospective study of human and murine neutrophils and clinical cohort analysis. Setting: University research laboratory and level 1 trauma center. Patients: Trauma patients, volunteer controls. Animal Subjects: C57Bl/6, formyl peptide receptor-1, and formyl peptide receptor-2 knockout mice. Interventions: Human and murine neutrophils functions were activated with autologous mitochondrial debris, mitochondrial formyl peptides, or bacterial formyl peptides followed by chemokines or leukotrienes. The experiments were repeated using formyl peptide receptor-1 antagonist cyclosporin H, “designer” human formyl peptide receptor-1 antagonists (POL7178 and POL7200), or anti-formyl peptide receptor-1 antibodies. Mouse injury/lung infection model was used to evaluate effect of formyl peptide receptor-1 inhibition. Measurements and Main Results: Human neutrophils cytosolic calcium, chemotaxis, reactive oxygen species production, and phagocytosis were studied before and after exposure to mitochondrial debris, mitochondrial formyl peptides, and bacterial formyl peptides. Mitochondrial formyl peptide and bacterial formyl peptides had similar effects on neutrophils. Responses to chemokines and leukotrienes were suppressed by prior exposure to formyl peptides. POL7200 and POL7178 were specific antagonists of human formyl peptide receptor-1 and more effective than cyclosporin H or anti-formyl peptide receptor-1 antibodies. Formyl peptides inhibited mouse neutrophils responses to chemokines only if formyl peptide receptor-1 was present. Formyl peptide receptor-1 blockade did not inhibit neutrophils bacterial phagocytosis or reactive oxygen species production. Cyclosporin H increased bacterial clearance in lungs after injury. Conclusions: Formyl peptides both activate and desensitize neutrophils. Formyl peptide receptor-1 blockade prevents desensitization, potentially both diminishing systemic inflammatory response syndrome and protecting the host against secondary infection after tissue trauma or primary infection. This work was performed at Beth Israel Deaconess Medical Center. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by Department of Defense Focused Program Award W81XWH-16-1-0464 (Drs. Yaffe, Otterbein, and Hauser) and National Institute of Allergy Infectious Diseases grant 1R03AI35346-01 (Dr. Itagaki). Dr. Itagaki has a grant from National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIH), 1R03AI135346-01. Drs. Itagaki, Kaczmarek, Wang, Gong, Gao, and Otterbein received support for article research from the NIH. Dr. Yaffe’s institution received funding from Department of Defense (DoD); he received funding from The American Association for the Advancement of Science Science Signaling and Applied Biomath; and he received support for article research from the DoD. Drs. Wang, Gong, and Gao disclosed government work. Dr. Otterbein received funding from HillHurst Biopharmaceuticals (stock options). Drs. Hauser and Otterbein share a grant from DoD, W81XWH-16-1-0464. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kitagaki@bidmc.harvard.edu; cjhauser@bidmc.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis Objectives: Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. Data Sources: Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. Study Selection and Data Extraction: Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. Data Synthesis: We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31–6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09–2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51–4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day). Conclusions: Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from National Institute for Health Research Nottingham Biomedical Research Centre, (Nottingham University Hospitals National Health Service Trust and University of Nottingham), Nottingham, United Kingdom. This article is based on a Cochrane Review published in the Cochrane Database of Systematic Reviews (CDSR) 2019; issue 2, DOI: 10.1002/14651858.CD010406. (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review. Dr. Lansbury disclosed that this work is part of an ongoing program undertaken by the Nottingham Biomedical Research Centre funded by the National Institute for Health Research (NIHR); she is the Head of the World Health Organization Collaborating Centre for Pandemic Influenza and Research at the University of Nottingham, which has a grant from the World Health Organization to provide technical assistance for the prevention and control of seasonal influenza; she has salary support funded by the NIHR; and she received support for article research from the NIHR. Dr. Rodrigo received salaries funded, in part, by an unrestricted grant from Pfizer and the NIHR. Professor Leonardi-Bee disclosed that she was a coapplicant on an educational grant from Hoffmann-La Roche to carry out research in the area of pandemic influenza. Hoffmann-La Roche did not support any aspects of this work. She also undertook consultancy work for the U.K. Food Standards Agency in 2013–2015 and for a Breast Milk Substitute manufacturer in 2017 to help them design a healthcare claim trial. Professor Nguyen-Van-Tam’s institution received funding from the NIHR. He disclosed that the University of Nottingham Health Protection Research Group currently holds an unrestricted educational grant for influenza research from F. Hoffmann-La Roche, but this did not support any aspect of this work. He also disclosed that he is a former employee of SmithKline Beecham plc (now GlaxoSmithKline), Roche Products, and Aventis-Pasteur MSD (now Sanofi-Pasteur MSD), all prior to 2005, with no outstanding pecuniary interests by way of shareholdings, share options, or accrued pension rights. He is currently on secondment to the Department of Health and Social Care (U.K. government); he received support for article research from NIHR, Nottingham Biomedical Research Centre; and he disclosed off-label product use of corticosteroids. Professor Lim’s institution received funding from NIHR Biomedical Research Centre and Pfizer (unrestricted investigator-initiated research grant for pneumococcal pneumonia) and the NIHR (corticosteroids in pandemic influenza clinical trial). This work was performed at the University of Nottingham, Nottingham, United Kingdom. Address requests for reprints to: Louise E. Lansbury, MBBS, PhD, Department of Epidemiology and Public Health, University of Nottingham, Room B104 Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, United Kingdom. E-mail: louise.lansbury@nottingham.ac.uk Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Suppression of Superoxide-Hydrogen Peroxide Production at Site IQ of Mitochondrial Complex I Attenuates Myocardial Stunning and Improves Postcardiac Arrest Outcomes Objectives: Cardiogenic shock following cardiopulmonary resuscitation for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of postcardiopulmonary resuscitation mortality. The pathophysiology of this shock is unclear, and effective therapies for improving clinical outcomes are lacking. Design: Laboratory investigation. Setting: University laboratory. Subjects: C57BL/6 adult female mice. Interventions: Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 4, 8, 12, or 16-minute potassium chloride-induced cardiac arrest followed by 90 seconds of cardiopulmonary resuscitation. Mice were then blindly randomized to a single IV injection of vehicle (phosphate-buffered saline) or suppressor of site IQ electron leak, an inhibitor of superoxide production by complex I of the mitochondrial electron transport chain. Suppressor of site IQ electron leak and vehicle were administered during cardiopulmonary resuscitation. Measurements and Main Results: Using a murine model of asystolic cardiac arrest, we discovered that duration of cardiac arrest prior to cardiopulmonary resuscitation determined postresuscitation success rates, degree of neurologic injury, and severity of myocardial dysfunction. Post-cardiopulmonary resuscitation cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening. Furthermore, left ventricular function recovered within 72 hours of cardiopulmonary resuscitation, indicative of myocardial stunning. Postcardiopulmonary resuscitation, the myocardium exhibited increased reactive oxygen species and evidence of mitochondrial injury, specifically reperfusion-induced reactive oxygen species generation at electron transport chain complex I. Suppressor of site IQ electron leak, which inhibits complex I-dependent reactive oxygen species generation by suppression of site IQ electron leak, decreased myocardial reactive oxygen species generation and improved postcardiopulmonary resuscitation myocardial function, neurologic outcomes, and survival. Conclusions: The severity of cardiogenic shock following asystolic cardiac arrest is dependent on the length of cardiac arrest prior to cardiopulmonary resuscitation and is mediated by myocardial stunning resulting from mitochondrial electron transport chain complex I dysfunction. A novel pharmacologic agent targeting this mechanism, suppressor of site IQ electron leak, represents a potential, practical therapy for improving sudden cardiac arrest resuscitation outcomes. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by National Institutes of Health RO1HL133675 (to Dr. Sharp). Dr. Archer is supported by the Canadian Institutes of Health Research, The Henderson Foundation, and the Queen’s Cardiopulmonary Unit. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wsharp@medicine.bsd.uchicago.edu This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners Objectives: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. Design: Multinational internet-assisted survey. Setting: Critical care practitioners involved with 14 societies in 80 countries. Subjects: Intensivists, nephrologists, advanced practice providers, ICU and dialysis nurses. Intervention: A cross-sectional survey. Measurement and Main Results: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2–22.0 yr). Two third of practitioners (71.0%; regional range, 55.0–95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0–111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0–365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7–47.8%) assessed hourly net fluid balance during continuous renal replacement therapy. Hemodynamic instability was reported in 20% (range, 20–38%) of patients and practitioners decreased the rate of fluid removal (70.3%); started or increased the dose of a vasopressor (51.5%); completely stopped fluid removal (35.8%); and administered a fluid bolus (31.6%), with significant regional variation. Compared with physicians, nurses were most likely to report patient intolerance to net ultrafiltration (73.4% vs 81.3%; p = 0.002), frequent interruptions (40.4% vs 54.5%; p < 0.001), and unavailability of trained staff (11.9% vs 15.6%; p = 0.04), whereas physicians reported unavailability of dialysis machines (14.3% vs 6.1%; p < 0.001) and costs associated with treatment as barriers (12.1% vs 3.0%; p < 0.001) with significant regional variation. Conclusions: Our study provides new knowledge about the presence and extent of international practice variation in net ultrafiltration. We also identified barriers and specific targets for quality improvement initiatives. Our data reflect the need for evidence-based practice guidelines for net ultrafiltration. Dr. Murugan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, and involved in drafting of the article, statistical analysis, and study supervision. Drs. Murugan, Ostermann, Peng, Puttarajappa, Weisbord, Palevsky, Kellum, and Bellomo were involved in study concept and design. Drs. Murugan, Ostermann, Peng, Kitamura, Romagnoli, Di Lullo, Srisawat, Todi, Bellomo, and Ronco were involved in acquisition of data. Drs. Murugan, Ostermann, Weisbord, Palevsky, Kellum, Bellomo, and Ronco were involved in analysis and interpretation of data. Drs. Murugan, Ostermann, Peng, and Kitamura were involved in administrative, technical, or material support. All authors were involved in critical revision of the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Murugan received grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases and Bioporto and funding from AM Pharma and La Jolla unrelated to this study. Dr. Romagnoli received funding from Baxter, MSD, and Masimo. Dr. Hoste’s institution received funding from AM Pharma and Sopachem. Dr. Bagshaw received funding from Baxter. Dr. Weisbord received funding from Saghmos Therapeutics. Drs. Weisbord and Palevsky disclosed government work. Dr. Palevsky’s institution received funding from Dascena, and he received funding from Baxter, Novartis, and GE Healthcare. Dr. Kellum received funding from Baxter (grant and consulting) and NxStage (consulting). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: muruganr@upmc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Conditional Survival With Increasing Duration of ICU Admission: An Observational Study of Three Intensive Care Databases Objectives: Prolonged admissions to an ICU are associated with high resource utilization and personal cost to the patient. Previous reports suggest increasing length of stay may be associated with poor outcomes. Conditional survival represents the probability of future survival after a defined period of treatment on an ICU providing a description of how prognosis evolves over time. Our objective was to describe conditional survival as length of ICU stay increased. Design: Retrospective observational cohort study of three large intensive care databases. Setting: Three intensive care databases, two in the United States (Medical Information Mart for Intensive Care III and electronic ICU) and one in United Kingdom (Post Intensive Care Risk-Adjusted Alerting and Monitoring). Patients: Index admissions to intensive care for patients 18 years or older. Interventions: None. Measurements and Main Results: A total of 11,648, 38,532, and 165,125 index admissions were analyzed from Post Intensive Care Risk-Adjusted Alerting and Monitoring, Medical Information Mart for Intensive Care III and electronic ICU databases respectively. In all three cohorts, conditional survival declined over the first 5–10 days after ICU admission and changed little thereafter. In patients greater than or equal to 75 years old conditional survival continued to decline with increasing length of stay. Conclusions: After an initial period of 5–10 days, probability of future survival does not decrease with increasing length of stay in unselected patients admitted to ICUs. These findings were consistent between the three populations and suggest that a prolonged admission to an ICU is not a reason for a pessimism in younger patients but may indicate a poor prognosis in the older population. Drs. Marshall, Young, and Watkinson designed the study. Drs. Marshall and Hatch and Mr. Gerry conducted the analysis. All authors were responsible for interpreting the data and drafting of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). This publication has been made possible through access to a research database that was created with support from the Health Innovation Challenge Fund (HICF-0510-006; WT-094951), a parallel funding partnership between the Department of Health and Wellcome Trust. Access was granted by the owners of the research database, the University of Oxford Critical Care Research Group. Dr. Young’s institution received funding from Health Innovation Challenge Fund (joint venture of Wellcome Trust and U.K. Department of Health. Dr. Watkinson’s institution received funding from Drayson Health and National Institute for Health Research (NIHR) Biomedical Research Center, Oxford, and he received funding from Drayson Health. Dr. Hatch is funded by an NIHR Academic Clinical Fellowship. Gerry is funded by an NIHR Doctoral Fellowship (DRF-2016-09-073). Dr. Watkinson has developed an electronic observations application for which Drayson Health (now Sensyne Health) has purchased a sole license. The company has a research agreement with the University of Oxford and pay personal fees. No other authors have financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, nor other relationships or activities that could appear to have influenced the submitted work. Dr. Marshall has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: dominic.marshall@bath.edu This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Investigating Swallowing and Tracheostomy Following Critical Illness: A Scoping Review Objectives: Tracheostomy and dysphagia often coexist during critical illness; however, given the patient’s medical complexity, understanding the evidence to optimize swallowing assessment and intervention is challenging. The objective of this scoping review is to describe and explore the literature surrounding swallowing and tracheostomy in the acute care setting. Data Sources: Eight electronic databases were searched from inception to May 2017 inclusive, using a search strategy designed by an information scientist. We conducted manual searching of 10 journals, nine gray literature repositories, and forward and backward citation chasing. Study Selection: Two blinded reviewers determined eligibility according to inclusion criteria: English-language studies reporting on swallowing or dysphagia in adults (≥ 17 yr old) who had undergone tracheostomy placement while in acute care. Patients with head and/or neck cancer diagnoses were excluded. Data Extraction: We extracted data using a form designed a priori and conducted descriptive analyses. Data Synthesis: We identified 6,396 citations, of which 725 articles were reviewed and 85 (N) met inclusion criteria. We stratified studies according to content domains with some featuring in multiple categories: dysphagia frequency (n = 38), swallowing physiology (n = 27), risk factors (n = 31), interventions (n = 21), and assessment comparisons (n = 12) and by patient etiology. Sample sizes (with tracheostomy) ranged from 10 to 3,320, and dysphagia frequency ranged from 11% to 93% in studies with consecutive sampling. Study design, sampling method, assessment methods, and interpretation approach varied significantly across studies. Conclusions: The evidence base surrounding this subject is diverse, complicated by heterogeneous patient selection methods, design, and reporting. We suggest ways the evidence base may be developed. This work was performed at the School of Audiology and Speech Sciences, University of British Columbia; University of Alberta Hospitals, Edmonton, AB, Canada. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by Dr. Skoretz’ School of Audiology and Speech Sciences startup funds from the University of British Columbia’s (UBC) Faculty of Medicine and UBC’s student Work Learn program. Dr. Dawson’s institution received funding from Queen Elizabeth Hospital Birmingham Charities. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sskoretz@audiospeech.ubc.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.