Emergency Department to ICU Time Is Associated With Hospital Mortality: A Registry Analysis of 14,788 Patients From Six University Hospitals in the Netherlands Objectives: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. Design, Setting, and Patients: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality. Interventions: None. Measurements and Main Results: A total of 14,788 patients were included. The median emergency department to ICU time was 2.0 hours (interquartile range, 1.3–3.3 hr). Emergency department to ICU time was correlated to adjusted hospital mortality (p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI, 1.02–1.64 (2.4–3.7 hr) and odds ratio, 1.54; 95% CI, 1.11–2.14 (> 3.7 hr), both compared with the reference category (< 1.2 hr). For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to adjusted ICU mortality (p = 0.20). Conclusions: Prolonged emergency department to ICU time (> 2.4 hr) is associated with increased hospital mortality after ICU admission, mainly driven by patients who had a higher Acute Physiology and Chronic Health Evaluation IV probability. We hereby provide evidence that rapid admission of the most critically ill patients to the ICU might reduce hospital mortality. 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). Drs. Termorshuizen’s and de Keizer’s institutions received funding from National Intensive Care Evaluation registry, and they received funding from Amsterdam UMC. Dr. Termorshuizen received funding from Mental Health Care Institute, GGZ Rivierduinen and Utrecht University, Utrecht Institute for Pharmaceutical Sciences. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: c.groenland@erasmusmc.nl This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Focused Subspecialty Critical Care Training Is Superior for Trainees and Patients No abstract available

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients Objectives: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. Design: Multicenter, prospective cohort study. Setting: The emergency department and ICUs of 15 medical centers. Patients: Mechanically ventilated adult emergency department patients. Interventions: None. Measurements and Main Results: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of –3 to –5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, –0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, –0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26–4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74–2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10–2.73). Conclusions: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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. Roberts’ institution received funding from National Heart, Lung, and Blood Institute (NHLBI) K23HL126979. Drs. Roberts, Pappal, Lokhandwala, and Tonna received support for article research from the National Institutes of Health (NIH). Dr. Knight received funding from Bard Medical and Genentech (speaker bureau for both). Dr. Pappal’s institution received funding from National Center for Advancing Translational Sciences of the NIH under Award Number UL1 TR002345. Dr. Johnson’s institution received funding from NHLBI and Medic One Foundation; he received funding from the NIH (U01HL123008-02). Dr. Lokhandwala was supported by NIH/NHLBI T32 HL007287-39. Dr. Hough’s institution received funding from the NIH (U01HL123008-02). Dr. Tonna was supported by a career development award (K23HL141596) from the NHLBI of the NIH, and, in part, by the University of Utah Study Design and Biostatistics Center, with funding in part from the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through Grant 5UL1TR001067-02 (formerly 8UL1TR000105 and UL1RR025764); he received funding from NIH/NSF and Philips Healthcare. Dr. Carpenter disclosed he is a Member of American College of Emergency Physicians Clinical Policy Committee, a Chair of Schwartz-Reisman Emergency Medicine Research Institute International Advisory Board, and a Speaker for Best Evidence in Emergency Medicine (continuing medical education [CME] product) and for Emergency Medical Abstracts (CME product). Dr. Avidan received funding from UptoDate. Dr. Kollef received funding from the Barnes-Jewish Hospital Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at Washington University School of Medicine in St. Louis, University of Iowa, Cooper University Hospital, University of New Mexico, The Cleveland Clinic, MedStar Washington Hospital Center, Christiana Care Health System, University of Cincinnati, Henry Ford Health System, University of Arizona/Banner University Medical Center-Tucson, Lahey Hospital & Medical Center, University of Washington Harborview Medical Center, University of Utah Health, University of Pennsylvania, Michigan Medicine. For information regarding this article, E-mail: fullerb@wustl.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Evaluation and Predictors of Fluid Resuscitation in Patients With Severe Sepsis and Septic Shock Objectives: Rapid fluid resuscitation has become standard in sepsis care, despite “low-quality” evidence and absence of guidelines for populations “at risk” for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived “at-risk” volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume “overload” by bedside examination. Design: Retrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics. Setting: Urban, tertiary care center between January 1, 2014, and May 31, 2017. Patients: Emergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock. Interventions: Administration of IV fluids by bolus. Measurements and Main Results: In total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46–0.83), male (odds ratio, 0.66; CI, 0.49–0.87), obese (odds ratio, 0.18; CI, 0.13–0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13–0.40), heart failure (odds ratio, 0.42; CI, 0.29–0.60), or documented volume “overload” (odds ratio, 0.30; CI, 0.20–0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03–2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02–1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5–3.6), without differential effects for “at-risk” groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05). Conclusions: Failure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation. 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 Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number 5UL1TR002389-02 that funds the Institute for Translational Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: maward@medicine.wisc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury Objectives: There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome. Design: Multicenter prospective registry. Setting: Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network. Patients: Eight-hundred one spinal cord injury patients enrolled by participating centers. Interventions: Appropriate spinal cord injury treatment at individual centers. Measurements and Main Results: A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32–0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17–36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35–13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19–17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31–14.32) measured using the Spinal Cord Independence Measure subscores. Conclusions: Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury. Drs. Jiang and Jaja contributed equally to this work and are co-first authors. 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). Christopher Reeve Foundation supports the North American Clinical Trials Network for the Treatment of Spinal Cord Injury and the AOSpine Spinal Cord Injury Knowledge Forum. Dr. Grossman received funding from InSightec. Dr. Guest’s institution received funding from North American Clinical Trials Network (NACTN); he received funding from the California Institute of Regenerative Medicine and Abbvie; and he received support for article research from NACTN. Dr. Shaffrey’s institution received funding from NACTN and Zimmer-Biomet, and he received funding from Medtronic, NuVasive, EOS, and Siemens. Dr. Toups’s institution received funding from the Department of Defense Joint Warfare Medical Research Program grant. Dr. Fehlings received funding from Fortuna Fix; he disclosed that the Christopher Reeve Foundation supports the NACTN for the Treatment of Spinal Cord Injury; and he would like to acknowledge support from the Gerry and Tootsie Halbert Chair in Neural Repair and Regeneration and the DeZwirek Family Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: michael.fehlings@uhn.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Comparing the McGrath Mac Video Laryngoscope and Direct Laryngoscopy for Prehospital Emergency Intubation in Air Rescue Patients: A Multicenter, Randomized, Controlled Trial Objectives: Tracheal intubation in prehospital emergency care is challenging. The McGrath Mac Video Laryngoscope (Medtronic, Minneapolis, MN) has been proven to be a reliable alternative for in-hospital airway management. This trial compared the McGrath Mac Video Laryngoscope and direct laryngoscopy for the prehospital setting. Design: Multicenter, prospective, randomized, controlled equivalence trial. Setting: Oesterreichischer Automobil- und Touring Club (OEAMTC) Helicopter Emergency Medical Service in Austria, 18-month study period. Patients: Five-hundred fourteen adult emergency patients (≥ 18 yr old). Interventions: Helicopter Emergency Medical Service physicians followed the institutional algorithm, comprising a maximum of two tracheal intubation attempts with each device, followed by supraglottic, then surgical airway access in case of tracheal intubation failure. No restrictions were given for tracheal intubation indication. Measurements Main Results: The Primary outcome was the rate of successful tracheal intubation; equivalence range was ± 6.5% of success rates. Secondary outcomes were the number of attempts to successful tracheal intubation, time to glottis passage and first end-tidal CO2 measurement, degree of glottis visualization, and number of problems. The success rate for the two devices was equivalent: direct laryngoscopy 98.5% (254/258), McGrath Mac Video Laryngoscope 98.1% (251/256) (difference, 0.4%; 99% CI, –2.58 to 3.39). There was no statistically significant difference with regard to tracheal intubation times, number of attempts or difficulty. The view to the glottis was significantly better, but the number of technical problems was increased with the McGrath Mac Video Laryngoscope. After a failed first tracheal intubation attempt, immediate switching of the device was significantly more successful than after the second attempt (90.5% vs 57.1%; p = 0.0003), regardless of the method. Conclusions: Both devices are equivalently well suited for use in prehospital emergency tracheal intubation of adult patients. Switching the device following a failed first tracheal intubation attempt was more successful than a second attempt with the same device. Drs. Kreutziger and Trimmel drafted, initiated, and designed the study, analyzed and interpreted the data, and drafted the article. Drs. Hornung, Harrer, Urschl, and Doppler assisted in collecting the data and revised the article. Dr. Voelckel participated in concept and design of the study, data interpretation, and critically revised the article. All authors read and approved the final 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). Supported, in part, by OEAMTC Helicopter Emergency Medical Service, who paid patient insurance premiums. Dr. Trimmel disclosed that the study was funded in part by Oesterreichischer Automobil- und Touring Club, the motorist association of Austria (OEAMTC) Helicopter Emergency Medical Service (patient insurance fees). The remaining authors have disclosed that they do not have any potential conflicts of interest. Ethics Committee Approval: The study was approved by the Ethics Committee of the State of Lower Austria (GS1-EK-3/124–2016). For information regarding this article, E-mail: Helmut.Trimmel@meduniwien.ac.at This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Association Between Sepsis and Microvascular Brain Injury Objectives: Many survivors of sepsis suffer long-term cognitive impairment, but the mechanisms of this association remain unknown. The objective of this study was to determine whether sepsis is associated with cerebral microinfarcts on brain autopsy. Design: Retrospective cohort study. Setting and Subjects: Five-hundred twenty-nine participants of the Adult Changes in Thought, a population-based prospective cohort study of older adults carried out in Kaiser Permanente Washington greater than or equal to 65 years old without dementia at study entry and who underwent brain autopsy. Measurements and Main Results: Late-life sepsis hospitalization was identified using administrative data. We identified 89 individuals with greater than or equal to 1 sepsis hospitalization during study participation, 80 of whom survived hospitalization and died a median of 169 days after discharge. Thirty percent of participants with one or more sepsis hospitalization had greater than two microinfarcts, compared with 19% participants without (χ2p = 0.02); 20% of those with sepsis hospitalization had greater than two microinfarcts in the cerebral cortex, compared with 10% of those without (χ2p = 0.01). The adjusted relative risk of greater than two microinfarcts was 1.61 (95% CI, 1.01–2.57; p = 0.04); the relative risk for having greater than two microinfarcts in the cerebral cortex was 2.12 (95% CI, 1.12–4.02; p = 0.02). There was no difference in Braak stage for neurofibrillary tangles or consortium to establish a registry for Alzheimer’s disease score for neuritic plaques between, but Lewy bodies were less significantly common in those with sepsis. Conclusions: Sepsis was specifically associated with moderate to severe vascular brain injury as assessed by microvascular infarcts. This association was stronger for microinfarcts within the cerebral cortex, with those who experienced severe sepsis hospitalization being more than twice as likely to have evidence of moderate to severe cerebral cortical injury in adjusted analyses. Further study to identify mechanisms for the association of sepsis and microinfarcts is needed. Dr. Ehlenbach 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. Dr. Ehlenbach helped in study concept and design, statistical analysis, and drafting of the article. Drs. Ehlenbach and Larson helped in administrative, technical, or material support and study supervision of the article. Drs. Ehlenbach, Montine, and Larson helped in obtained funding. All authors helped in acquisition, analysis, or interpretation of data and critical revision of the article for important intellectual content. Supported, in part, by the National Institutes of Health (NIH), National Institute of Aging, The Atlantic Philanthropies, The John A. Hartford Foundation, and the Starr Foundation (K23AG038352, principal investigator [PI] Dr. Ehlenbach). Additional support provided by P50AG005136 (PI Dr. Grabowski) and NIH U01AG006781 (PI Dr. Larson). Dr. Ehlenbach’s institution received funding from the National Institutes of Health (NIH). Dr. Larson’s institution received funding from the National Institute on Aging, and he received funding from UptoDate (royalties). Drs. Ehlenbach, Sonnen, Montine, and Larson report grants from the NIH paid to their institutions. For information regarding this article, E-mail: wjehlenb@wisc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Core Outcome Measures for Research in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation for Acute Respiratory or Cardiac Failure: An International, Multidisciplinary, Modified Delphi Consensus Study Objectives: Research evaluating outcomes in critically ill patients with acute respiratory and cardiac failure supported with extracorporeal membrane oxygenation has increased significantly. The objective was to identify a core set of outcomes that are essential to include in all clinical research evaluating the use of either venoarterial or venovenous extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events. Design: A three-round modified Delphi process. Subjects: Patients, caregivers, multidisciplinary clinicians, researchers, industry partners, and research funders were included. Setting: Participants represented key extracorporeal membrane oxygenation organizations, including the Extracorporeal Life Support Organization, the International Extracorporeal Membrane Oxygenation Network, clinicians from high volume extracorporeal membrane oxygenation centers, and extracorporeal membrane oxygenation researchers or former extracorporeal membrane oxygenation patients from five continents. Interventions: We used recommended standards for the development of a core outcome set. Outcome measures identified from systematic reviews of the literature and from qualitative studies of survivors were mapped to the domains identified by the Core Outcome Measures in Effectiveness Trials initiative separately for venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. Measurements and Main Results: Participant response rates were 40 of 47 (85%), 35 of 37 (95%), and 64 of 69 (93%) for survey rounds 1, 2, and 3, respectively, with participants representing 10 different countries on five continents. After the third round survey, 8 outcome measures met consensus for both venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation. Conclusions: This study identified core outcomes to assess in all research evaluating the use of extracorporeal membrane oxygenation, including adverse events specific to this intervention, permitting standardization of outcome reporting for the first time. Identifying appropriate measurement instruments to evaluate these outcomes is an important next step to enable synthesis of extracorporeal membrane oxygenation research. This work was performed at the Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, VIC, Australia. Drs. Hodgson, Brodie, and Fan conceived of the study. All authors designed the study and assisted with data acquisition and interpretation. All authors drafted and revised the article for intellectual content. All authors approved the final version and are accountable for the accuracy and integrity of the data. 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 International Extracorporeal Membrane Oxygenation (ECMO) Network and The Hearts of ECMO. Dr. Hodgson reports grants from Hearts of ECMO and the Heart Foundation of Australia during the conduct of the study. Dr. Pellegrino received funding from Xenios. Dr. Brodie reports receiving research support from ALung Technologies, personal fees from Baxter, anticipated personal fees from BREETHE, unpaid advising for Hemovent, and he disclosed off-label product use of ECMO. Dr. Fan is supported by a New Investigator Award from the Canadian Institutes of Health Research and has received personal fees from Abbott, ALung Technologies, and MC3 Cardiopulmonary outside the submitted work. The remaining authors have disclosed that they do not have any conflicts of interest. For information regarding this article, E-mail: carol.hodgson@monash.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

End-of-Life Decision-Making for ICU Patients With Limited English Proficiency: A Qualitative Study of Healthcare Team Insights Objectives: Research indicates that the increasing population of over 25 million people in the United States who have limited English proficiency experience differences in decision-making and subsequent care at end of life in the ICU when compared with the general population. The objective of this study was to assess the perceptions of healthcare team members about the factors that influence discussions and decision-making about end of life for patients and family members with limited English proficiency in the ICU. Design: Qualitative study using semistructured interviews with ICU physicians, nurses, and interpreters. Setting: Three ICUs at Mayo Clinic Rochester. Subjects: Sixteen ICU physicians, 12 ICU nurses, and 12 interpreters. Intervention: None. Measurements and Main Results: We conducted 40 semistructured interviews. We identified six key differences in end-of-life decision-making for patients with limited English proficiency compared with patients without limited English proficiency: 1) clinician communication is modified and less frequent; 2) clinician ability to assess patient and family understanding is impaired; 3) relationship building is impaired; 4) patient and family understanding of decision-making concepts (e.g., palliative care) is impaired; 5) treatment limitations are often perceived to be unacceptable due to faith-based and cultural beliefs; and 6) patient and family decision-making styles are different. Facilitators of high-quality decision-making in patients with limited English proficiency included: 1) premeeting between clinician and interpreter; 2) interpretation that communicates empathy and caring; 3) bidirectional communication of cultural perspectives; 4) interpretation that improves messaging including appropriate word choice; and 5) clinician cultural humility. Conclusions: End-of-life decision-making is significantly different for ICU patients with limited English proficiency. Participants identified several barriers and facilitators to high-quality end-of-life decision-making for ICU patients and families with limited English proficiency. Awareness of these factors can facilitate interventions to improve high-quality, compassionate, and culturally sensitive decision-making for patients and families with limited English proficiency. This work was performed at the Mayo Clinic, Rochester, MN. 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 TL1 TR002380 from the National Center for Advancing Translational Sciences and from the Mayo Clinic Critical Care Research Committee. Dr. Barwise and Ms. Nyquist received funding from an institutional critical care research committee grant (Mayo Clinic Critical Care Research Committee). This study was supported by the National Center for Advancing Translational Sciences Grant Number TL1 TR002380. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Dr. Thorsteinsdottir’s institution received funding from National Institute on Aging K23 AG051679 training award, and she received support for article research from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Amelia K. Barwise, MBBCh, BAO, MS, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: barwise.amelia@mayo.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

A Machine Learning Algorithm to Predict Severe Sepsis and Septic Shock: Development, Implementation, and Impact on Clinical Practice Objectives: Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes. Design: Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. Setting: Tertiary teaching hospital system in Philadelphia, PA. Patients: All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184). Interventions: A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. Measurement and Main Result: Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic blood pressure less than 90 mm Hg. The algorithm demonstrated a sensitivity of 26% and specificity of 98%, with a positive predictive value of 29% and positive likelihood ratio of 13. The alert resulted in a small statistically significant increase in lactate testing and IV fluid administration. There was no significant difference in mortality, discharge disposition, or transfer to ICU, although there was a reduction in time-to-ICU transfer. Conclusions: Our machine learning algorithm can predict, with low sensitivity but high specificity, the impending occurrence of severe sepsis and septic shock. Algorithm-generated predictive alerts modestly impacted clinical measures. Next steps include describing clinical perception of this tool and optimizing algorithm design and delivery. Drs. Giannini, Ginestra, Chivers, Draugelis, Schweickert, Fuchs, Meadows, Lynch, Donnelly, Pavan, Fishman, Hanson, and Umscheid contributed to conception and design. Drs. Giannini, Ginestra, Chivers, Draugelis, Hanish, Meadows, Lynch and Donnelly contributed to data collection. Drs. Giannini, Ginestra, Chivers, Draugelis, and Umscheid contributed to analysis and interpretation of data. Drs. Giannini, Ginestra, Chivers, and Umscheid contributed to drafting of article. Drs. Giannini, Ginestra, and Umscheid contributed to critical revision of 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). Supported, in part, by the National Center for Research Resources (grant no. UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no. UL1TR000003). Dr. Umscheid received support for article research from the National Institutes of Health. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Schweickert received funding from Arjo, Hill Rom, the Society of Critical Care Medicine (consulting), and American College of Physicians. Dr. Umscheid’s institution received funding from National Center for Research Resources (grant no. UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no. UL1TR000003); Agency for Healthcare Research and Quality Contracts Evidence-based Practice Center; and the U.S. Food and Drug Administration. He received funding from PCORI Advisory Panel and Northwell Health (honoraria for grand rounds). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Craig A. Umscheid, MD, MS, Office of Clinical Excellence, University of Chicago Medicine, American School Building, 850 E. 58th Street, Suite 123, Office 128, MC 1135, Chicago, IL 60637. E-mail: craigumscheid@medicine.bsd.uchicago.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.