Quantifiable Bleeding in Children Supported by Extracorporeal Membrane Oxygenation and Outcome Objectives: To evaluate the association between bleeding from chest tubes and clinical outcomes in children supported by extracorporeal membrane oxygenation. Design: Secondary analysis of a large observational cohort study. Setting: Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Collaborative Pediatric Critical Care Research Network. Patients: Critically ill children supported by extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Daily chest tube bleeding, results from hemostatic assays, transfusion volumes, 90-day PICU-free days, and mortality were collected prospectively by trained bedside extracorporeal membrane oxygenation specialists and research coordinators. Extracorporeal membrane oxygenation was employed in the care of 514 consecutive patients. Sixty percent of patients had at least one episode of chest tube bleeding (median chest tube blood volume over the entire extracorporeal membrane oxygenation course was 123 mL/kg [interquartile range, 47–319 mL/kg]). Twenty-six percent had at least 1 day of bleeding from the chest tube greater than 100 mL/kg/d. The number of days with chest tube bleeding greater than 60 mL/kg/d was independently associated with increased in-hospital mortality (adjusted odds ratio, 1.43; 95% CI, 1.05–1.97; p = 0.02) and decreased PICU-free days (beta coefficient, –4.2; 95% CI, –7.7 to –0.6; p = 0.02). The total amount of bleeding from chest tube were independently associated with increased mortality (per mL/kg/extracorporeal membrane oxygenation run; adjusted odds ratio, 1.002; 95% CI, 1.000–1.003; p = 0.04). Fibrinogen, weight, indication for extracorporeal membrane oxygenation, and need for hemodialysis were independently associated with chest tube bleeding, whereas platelet count, coagulation tests, heparin dose, and thrombotic events were not. Conclusions: In children supported by extracorporeal membrane oxygenation, chest tube bleeding above 60 mL/kg/d was independently associated with worse clinical outcome. Low fibrinogen was independently associated with chest tube bleeding, whereas platelet count and hemostatic tests were not. Further research is needed to evaluate if interventions to prevent or stop chest tube bleeding influence the clinical outcome. 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 Collaborative Pediatric Critical Care Research Network was funded by the National Institute of Child Health and Human Development (NICHD). This article does not necessarily reflect the opinions or views of the Bleeding and Thrombosis During Extracorporeal Membrane Oxygenation Investigators or the NICHD. Dr. Dalton received funding from Innovative Extracorporeal Membrane Oxygenation Concepts, 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. For information regarding this article, E-mail: man9026@med.cornell.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

RBC Transfusion Strategies in the ICU: A Concise Review Objectives: To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU. Data Sources: Source data were obtained from a PubMed literature review. Study Selection: English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies. Data Extraction: Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice. Data Synthesis: Approximately 30–50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion. Conclusions: The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients. New affiliation for Dr. Murphy: Division of Pulmonary Diseases and Critical Care Medicine, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA. Drs. Cable and Murphy received support for article research from the National Institutes of Health (NIH). Dr. Cable’s institution received funding from NIH/National Institute of General Medical Sciences T32 GM-095442. Dr. Roback’s institution received funding from the NIH and Zipline Medical, and he received funding from CSL Plasma and Castle Medical. Dr. Murphy’s institution received funding from the NIH. Dr. Razavi disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: david.j.murphy@emory.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Enteral Nutrition Can Be Given to Patients on Vasopressors No abstract available

Nurse Practitioners and Physician Assistants in Acute and Critical Care: A Concise Review of the Literature and Data 2008–2018 Objectives: To provide a concise review of the literature and data pertaining to the use of nurse practitioners and physician assistants, collectively called advanced practice providers, in ICU and acute care settings. Data Sources: Detailed search strategy using the databases PubMed, Ovid MEDLINE, and the Cumulative Index of Nursing and Allied Health Literature for the time period from January 2008 to December 2018. Study Selection: Studies addressing nurse practitioner, physician assistant, or advanced practice provider care in the ICU or acute care setting. Data Extraction: Relevant studies were reviewed, and the following aspects of each study were identified, abstracted, and analyzed: study population, study design, study aims, methods, results, and relevant implications for critical care practice. Data Synthesis: Five systematic reviews, four literature reviews, and 44 individual studies were identified, reviewed, and critiqued. Of the research studies, the majority were retrospective with others being observational, quasi-experimental, or quality improvement, along with two randomized control trials. Overall, the studies assessed a variety of effects of advanced practice provider care, including on length of stay, mortality, and quality-related metrics, with a majority demonstrating similar or improved patient care outcomes. Conclusions: Over the past 10 years, the number of studies assessing the impact of advanced practice providers in acute and critical care settings continue to increase. Collectively, these studies identify the value of advanced practice providers in patient care management, continuity of care, improved quality and safety metrics, patient and staff satisfaction, and on new areas of focus including enhanced educational experience of residents and fellows. 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. Kleinpell received funding from the Society of Critical Care Medicine (SCCM) (past 2017 president). Dr. Constantine disclosed that he was on the Board of the Council of Surgical and Perioperative Safety and chaired the safety committee for the Surgery Section of the SCCM and the SCCM Advanced Practice Provider Resource Committee. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Ruth M. Kleinpell, PhD, RN, Vanderbilt University School of Nursing, 461 21st Avenue, South 407 GH, Nashville, TN 37240. E-mail: ruth.kleinpell@vanderbilt.edu 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.

National Trends in Timing of Death Among Patients With Septic Shock, 1994–2014 Objectives: To assess trends in timing of mortality among patients with septic shock. Design: Retrospective cohort study. Setting: Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project’s National Inpatient Sample, 1994–2014. Patients: Hospitalized adults (≥ 18 yr) with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with septic shock; secondary analysis: adults with International Classification of Diseases, 9th Edition, Clinical Modification codes consistent with acute respiratory failure receiving invasive mechanical ventilation and patients with both septic shock and acute respiratory failure receiving invasive mechanical ventilation. Interventions: None. Measurements and Main Results: From 1994 to 2014, 48-hour mortality rates decreased among patients with septic shock (21.2% to 10.8%) and septic shock with acute respiratory failure receiving invasive mechanical ventilation (19.1% to 13.4%) but increased among patients with acute respiratory failure receiving invasive mechanical ventilation (7.9% to 9.8%; p value for all trends, < 0.001). Three-to-14-day mortality decreased among patients with septic shock (22.1% to 15.5%), septic shock with acute respiratory failure receiving invasive mechanical ventilation (28.7% to 22.4%) and acute respiratory failure receiving invasive mechanical ventilation (16.8% to 15.0%; p value for all trends, < 0.001). Mortality after 14 days decreased among all groups (septic shock: 12.6% to 6.7%; septic shock with acute respiratory failure receiving invasive mechanical ventilation: 20.3% to 11.3%; and acute respiratory failure receiving invasive mechanical ventilation: 12.7% to 5.8%; p value for all trends, < 0.001). Cox proportional hazard ratio for declining risk in mortality per year (adjusted for patient and hospital characteristics) was 0.96 (95% CI, 0.96–0.96) for septic shock, 0.97 (0.97–0.97) for acute respiratory failure receiving invasive mechanical ventilation and septic shock, and 0.99 (0.99–0.99) for acute respiratory failure receiving invasive mechanical ventilation. Conclusions: Septic shock 48-hour, 3–14-day and greater than 14-day mortality declined markedly over two decades; in contrast, patients with acute respiratory failure only experienced marked decreases in greater than 14-day in-hospital mortality rates. 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. Law received funding from National Institutes of Health (NIH)/National Institute on Aging (1F32AG058352). Dr. Stevens received funding from Agency for Healthcare Research and Quality (5K08HS024288) and Doris Duke Charitable Foundation. Dr. Walkey received funding from NIH/National Heart, Lung, and Blood Institute (1R01HL136660 and 1R01HL139751) and Boston University School of Medicine Department of Medicine Career Investment Award. For information regarding this article, E-mail: alaw1@bidmc.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Antibiotic Exposure Profiles in Trials Comparing Intensity of Continuous Renal Replacement Therapy Objectives: To determine whether the probability of target attainment over 72 hours of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, meropenem) antibiotics were substantially influenced between intensive and less-intensive continuous renal replacement therapy groups in the Acute Renal Failure Trial Network trial and The RENAL Replacement Therapy Study trial. Design: The probability of target attainment was calculated using pharmacodynamic targets of percentage of time that free serum concentrations (fT): 1) were above the target organism’s minimum inhibitory concentration (≥ fT > 1 × minimum inhibitory concentration); 2) were above four times the minimum inhibitory concentration (≥ % fT > 4 × minimum inhibitory concentration); and 3) were always above the minimum inhibitory concentration (≥ 100% fT > minimum inhibitory concentration) for the first 72 hours of antibiotic therapy. Demographic data and effluent rates from the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials were used. Optimal doses were defined as the dose achieving greater than or equal to 90% probability of target attainment. Setting: Monte Carlo simulations using demographic data from Acute Renal Failure Trial Network and RENAL Replacement Therapy Study trials. Patients: Virtual critically ill patients requiring continuous renal replacement therapy. Interventions: None. Measurements and Main Results: The pharmacodynamic target of fT greater than 1 × minimum inhibitory concentration led to similarly high rates of predicted response with antibiotic doses often used in continuous renal replacement therapy. Achieving 100% fT greater than minimum inhibitory concentration is a more stringent benchmark compared with T greater than 4 × minimum inhibitory concentration with standard antibiotic dosing. The intensity of effluent flow rates (less intensive vs intensive) did not substantially influence the probability of target attainment of antibiotic dosing regimens regardless of pharmacodynamic target. Conclusions: Antibiotic pharmacodynamic target attainment rates likely were not meaningfully different in the low- and high-intensity treatment arms of the Acute Renal Failure Trial Network and RENAL Replacement Therapy Study Investigators trials. This work was performed at University of Michigan College of Pharmacy, Ann Arbor, MI. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: muellerb@umich.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

The Case for Broad Subspecialty Training No abstract available

One-Year Outcomes Following Tracheostomy for Acute Respiratory Failure Objectives: Tracheostomy utilization has dramatically increased recently. Large gaps exist between expected and actual outcomes resulting in significant decisional conflict and regret. We determined 1-year patient outcomes and healthcare utilization following tracheostomy to aid in decision-making and resource allocation. Design: Retrospective cohort study. Setting: All California hospital discharges from 2012 to 2013 with follow-up through 2014. Patients: Nonsurgical patients who received a tracheostomy for acute respiratory failure. Interventions: None. Measurements and Main Results: Our primary outcome was 30-day, 90-day, and 1-year mortality. We also determined hospitals readmissions rates and healthcare utilization in the first year following tracheostomy. We identified 8,343 tracheostomies during the study period. One-year mortality following tracheostomy was high, 46.5%. Older adults (≥ 65 yr) had significantly higher mortality compared with younger patients (< 65 yr) (54.7% vs 36.5%; p < 0.0001). Median survival for older adults was 175 days (95% CI, 150–202 d) compared with greater than 1 year for younger adults (adjusted hazard ratio, 1.25; 95% CI, 1.14–1.36). Within 1 year of tracheostomy, 60.3% of patients required hospital readmission. Older adults were more likely to be readmitted in the first year after tracheostomy compared with younger adults (66.1% vs 55.2%; adjusted hazard ratio, 1.19; 95% CI, 1.09–1.29). Total short-term acute care hospital costs (index and readmissions) in the first year after tracheostomy were high (mean, $215,369; SD, $160,874). Conclusions: Long-term outcomes following tracheostomy are extremely poor with high mortality, morbidity, and healthcare resource utilization especially among older patients. Some subsets of younger patients may have better outcomes compared with the general tracheostomy population. Short-term acute care costs were extremely high in the first year following tracheostomy. If extended to the entire U.S. population, total short-term acute care hospital costs approach $11 billion dollars per year for tracheostomy-related to acute respiratory failure. These findings may aid families and surrogates in the decision-making process. This work was performed at National Jewish Health. Dr. Mehta was involved in study design, data analysis, interpretation, and article preparation; he takes full responsibility for the content of the article, data analysis, and data interpretation; he 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 analysis; and he was responsible for drafting of the article. Dr. Walkey involved in data interpretation and article preparation. Dr. Curran-Everett involved in statistical and data interpretation. Dr. Douglas involved in study design, data interpretation, and article preparation. Drs. Mehta and Douglas were responsible for the study design. Drs. Mehta and Curran-Everett were responsible for the statistical analysis. All authors participated in data interpretation and contributed to critical revisions 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). Drs. Mehta, Curran-Everett, Douglas received support for article research from the National Institutes of Health (NIH) (K12HL137862, RHL089897B, and R01NR016459). Dr. Walkey’s institution received funding from the NIH (R01HL136660), and he received funding from UptoDate. For information regarding this article, E-mail: mehtaa@njhealth.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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