Optimizing Mean Arterial Pressure in Acutely Comatose Patients Using Cerebral Autoregulation Multimodal Monitoring With Near-Infrared Spectroscopy Objectives: This study investigated whether comatose patients with greater duration and magnitude of clinically observed mean arterial pressure outside optimal mean arterial blood pressure have worse outcomes than those with mean arterial blood pressure closer to optimal mean arterial blood pressure calculated by bedside multimodal cerebral autoregulation monitoring using near-infrared spectroscopy. Design: Prospective observational study. Setting: Neurocritical Care Unit of the Johns Hopkins Hospital. Subjects: Acutely comatose patients secondary to brain injury. Interventions: None. Measurements and Main Results: The cerebral oximetry index was continuously monitored with near-infrared spectroscopy for up to 3 days. Optimal mean arterial blood pressure was defined as that mean arterial blood pressure at the lowest cerebral oximetry index (nadir index) for each 24-hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of mean arterial blood pressure outside optimal mean arterial blood pressure and the absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure. A total 91 comatose patients were enrolled in the study. The most common etiology was intracerebral hemorrhage. Optimal mean arterial blood pressure could be calculated in 89 patients (97%), and the median optimal mean arterial blood pressure was 89.7 mm Hg (84.6–100 mm Hg). In multivariate proportional hazard analysis, duration outside optimal mean arterial blood pressure of greater than 80% of monitoring time (adjusted hazard ratio, 2.13; 95% CI, 1.04–4.41; p = 0.04) and absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure of more than 10 mm Hg (adjusted hazard ratio, 2.44; 95% CI, 1.21–4.92; p = 0.013) were independently associated with mortality at 3 months, after adjusting for brain herniation, admission Glasgow Coma Scale, duration on vasopressors and midline shift at septum. Conclusions: Comatose neurocritically ill adults with an absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure greater than 10 mm Hg and duration outside optimal mean arterial blood pressure greater than 80% had increased mortality at 3 months. Noninvasive near-infrared spectroscopy-based bedside calculation of optimal mean arterial blood pressure is feasible and might be a promising tool for cerebral autoregulation oriented-therapy in neurocritical care patients. Drs. Hogue and Ziai are senior 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). Supported, in part, by grant from the American Academy of Neurology/American Brain Foundation. Dr. Rivera-Lara’s institution received funding from American Academy of Neurology/American Brain Foundation and equipment from a Covidien/Medtronic grant. Dr. Brown’s institution received funding from National Institutes of Health (NIH)/National Institute on Aging and Medtronic. Drs. Brown and Hogue received support for article research from the NIH. Dr. Hogue is the PI on an NIH-sponsored clinical study (R01 HL 92259); he received funding from Medtronic/Covidien, Dublin, IR (advisor and lecturer), Merck (Data Safety and Monitoring Board for unrelated drug trial); he serves as a consultant to Medtronic/Covidien and Ornim Medical, Foxborough, MA; he received other support from Medtronic in the form of a near-infrared spectroscopy sensor; and he disclosed off-label product use of autoregulation monitoring. Dr. Ziai received funding form HeadSense. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: lriver14@jhmi.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Are Peripherally Inserted Central Catheters Suitable for Cardiac Output Assessment With Transpulmonary Thermodilution? Objectives: Peripherally inserted central catheters are increasingly used in ICU as an alternative to centrally inserted central catheters for IV infusion. However, their reliability for hemodynamic measurements with transpulmonary thermodilution is currently unknown. We investigated the agreement between transpulmonary thermodilution measurements obtained with bolus injection through peripherally inserted central catheter and centrally inserted central catheter (reference standard) using a transpulmonary thermodilution–calibrated Pulse Contour hemodynamic monitoring system (VolumeView/EV1000). Design: Prospective method-comparison study. Setting: Twenty-bed medical-surgical ICU of a teaching hospital. Patients: Twenty adult ICU patients who required hemodynamic monitoring because of hemodynamic instability and had both peripherally inserted central catheter and centrally inserted central catheter in place. Intervention: The hemodynamic measurements obtained by transpulmonary thermodilution after injection of a cold saline bolus via both centrally inserted central catheter and either a single-lumen 4F or a double-lumen 5F peripherally inserted central catheter using were compared. In order to rule out bias related to manual injection, measurements were repeated using an automated rapid injection system. Measurements and Main Results: A total of 320 measurements were made. Cardiac index was significantly higher when measured with double-lumen 5F peripherally inserted central catheter than with centrally inserted central catheter (mean, 4.5 vs 3.3 L/min/m2; p < 0.0001; bias, 1.24 L/min/m2 [0.27, 2.22 L/min/m2]; bias percentage, 31%). Global end-diastolic index, extravascular lung water index, and stroke volume index were also overestimated (853 ± 240 vs 688 ± 175 mL/m2, 12.2 ± 4.2 vs 9.4 ± 2.9 mL/kg, and 49.6 ± 14.9 vs 39.5 ± 9.6 mL/m2, respectively; p < 0.0001). Lower, albeit significant differences were found using single-lumen 4F peripherally inserted central catheter (mean cardiac index, 4.2 vs 3.7 L/min/m2; p = 0.043; bias, 0.51 L/min/m2 [–0.53, 1.55 L/min/m2]; bias percentage, 12.7%). All differences were confirmed, even after standardization of bolus speed with automated injection. Conclusions: Bolus injection through peripherally inserted central catheter for transpulmonary thermodilution using EV1000 led to a significant overestimation of cardiac index, global end-diastolic index, extravascular lung water index, and stroke volume index, especially when double-lumen 5F peripherally inserted central catheter was used (ClinicalTrial.gov NCT03834675). Drs. D’Arrigo and Sandroni contributed equally. 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 authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sonia.darrigo@virgilio.it; sonia.darrigo@policlinicogemelli.it Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Practice Patterns and Ethical Considerations in the Management of Venovenous Extracorporeal Membrane Oxygenation Patients: An International Survey Objectives: To characterize physicians’ practices and attitudes toward the initiation, limitation, and withdrawal of venovenous extracorporeal membrane oxygenation for severe respiratory failure and evaluate factors associated with these attitudes. Design: Electronic, cross-sectional, scenario-based survey. Setting: Extracorporeal membrane oxygenation centers affiliated with the Extracorporeal Life Support Organization and the International Extracorporeal Membrane Oxygenation Network. Subjects: Attending-level physicians with experience managing adult patients receiving venovenous extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Five-hundred thirty-nine physicians in 39 countries across six continents completed the survey. Factors that influenced the decision to limit extracorporeal membrane oxygenation initiation included older patient age (46.9%), additional organ failures (37.7%), and prolonged mechanical ventilation (35.1%). Patient comorbidities (70.5%), patient’s wishes (56.0%), and etiology of respiratory failure (37.7%) were factors that influenced the decision to withdraw extracorporeal membrane oxygenation. In multivariable analysis, factors associated with increased odds of withdrawing life-sustaining therapies included pulmonary fibrosis, stroke, surrogate’s desire to withdraw, lack of knowledge regarding patient’s or surrogate’s wishes in the setting of fibrosis, not initiating extracorporeal membrane oxygenation in the baseline scenario, and respondent religiosity. Factors associated with decreased odds of withdrawal included practicing in an environment where it is not legally possible to make decisions against patient or surrogate wishes. Most respondents (90.5%) involved other physicians in treatment decisions for extracorporeal membrane oxygenation patients, whereas only 53.2%, 45.3%, and 29.5% of respondents involved surrogates, awake patients, or bedside nurses, respectively. Conclusions: Patient and physician-level factors were associated with decision-making regarding extracorporeal membrane oxygenation initiation and withdrawal, including patient prognosis and knowledge of patient or surrogate wishes. Respondents reported low rates of engaging in shared decision-making when managing patients receiving extracorporeal membrane oxygenation. Drs. Brodie and Schmidt are co-senior authors. International ECMO Network (ECMONet) board members are: Daniel Brodie, Chair of Executive Committee; and Arthur S. Slutsky, Chair of Scientific Committee. Executive Committee Members are: Laurent Brochard, Daniel Brodie, Alain Combes, Eddy Fan, Niall Ferguson, John Fraser, Carol Hodgson, Danny McAuley, Alain Mercat, Thomas Mueller, Vin Pellegrino, Antonio Pesenti, Michael Quintel, V. Marco Ranieri, and Arthur S. Slutsky. Drs. Abrams, Combes, Curtis, Mueller, Serra, Brodie, and Schmidt were responsible for study design and development of the questionnaire. Drs. Abrams, Serra, and Schmidt were responsible for data collection. Drs. Pham, Burns, and Schmidt performed data analysis. Drs. Abrams, Pham, Burns, Brodie, and Schmidt drafted the article. Drs. Pham and Schmidt designed the figures. Drs. Abrams, Pham, Burns, Combes, Curtis, Mueller, Prager, Serra, Slutsky, Brodie, and Schmidt reviewed and edited the article. Dr. Abrams collated edits and prepared the article for submission. All authors approve the final version. The corresponding author (Dr. Schmidt) had full access to all the data in the study and had final responsibility for the decision to submit for publication. 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. Combes reports grants and personal fees from Maquet, grants and personal fees from Baxter, personal fees from Hemovent, outside the submitted work. Dr. Slutsky reports personal fees from Baxter Healthcare, personal fees from Xenios/NovaLung, personal fees from Maquet Critical Care, outside the submitted work. Dr. Brodie reports fees to his university from ALung Technologies, personal fees from Baxter and anticipated fees from Breethe, Inc. unpaid association with Hemovent, outside the submitted work. Dr. Schmidt reports personal fees from Getinge, personal fees from Drager, outside the submitted work. Drs. Abrams and Brodie disclosed off-label product use of extracorporeal membrane oxygenation for severe respiratory failure. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: matthieu.schmidt@aphp.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Clinical Examination for the Prediction of Mortality in the Critically Ill: The Simple Intensive Care Studies-I Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves (AUC). Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. Main Results: A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (AUC = 0.74; 95% CI, 0.71–0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (SAPS-II) (AUC = 0.76; 95% CI, 0.73–0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (APACHE-IV) (AUC = 0.77; 95% CI, 0.74–0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (SOFA) (AUC = 0.67; 95% CI, 0.64–0.71; p < 0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the SAPS-II and APACHE-IV and outperformed the SOFA score. New affiliation for Dr. Eck: Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Drs. Hiemstra, van der Horst, and Keus drafted the manuscript and conducted the analyses. Drs. van der Horst and Keus created the idea of the study. Drs. Eck and Koster developed the protocol and implemented the study. Mr. Wiersema and Dr. Kaufmann contributed substantially to the data collection. Drs. Wetterslev and Snieder contributed to the statistical analyses and design of the detailed statistical analyses plan. Professors Scheeren, Perner, and Pettilä critically reviewed the article. All authors critically reviewed the article and agreed with the final version and findings. 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). Prof dr. Scheeren received research funding and honoraria from Edwards Lifesciences and Masimo Inc. (Irvine, CA) for consulting and lecturing and from Pulsion Medical Systems SE for lecturing in the past. The remaining authors have disclosed that they do not have any potential conflicts of interest. Ethics approval: Medisch Ethische Toetsingscommissie, University Medical Center Groningen; METc M15.168207. ORCID IDs: Dr. Hiemstra: 0000-0001-6547-2138; Dr. Eck: 0000-0001-7440-2465; Mr. Wiersema: 0000-0003-2413-2852; Dr. Kaufmann: 0000-0003-0589-8879; Dr. Koster: 0000-0002-8927-3077; Dr. Scheeren: 0000-0002-9184-4190; Dr. Snieder; 0000-0003-1949-2298; Dr. Perner: 0000-0002-4668-0123; Dr. Wetterslev: 0000-0001-7778-1771; Dr. Keus: 0000-0003-1516-1475; Dr. van der Horst: 0000-0003-3891-8522. For information regarding this article, E-mail: b.hiemstra01@umcg.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.

Association Between the Use of Sodium Bicarbonate and Mortality in Acute Kidney Injury Using Marginal Structural Cox Model Objective: Acute kidney injury with metabolic acidosis is common in critically ill patients. This study assessed the associations between the use of IV sodium bicarbonate and mortality of patients with acute kidney injury and acidosis. Design: The study was conducted by using data from Beth Israel Deaconess Medical Center, which included several ICUs such as coronary care unit, cardiac surgery recovery unit, medical ICU, surgical ICU, and trauma-neuro ICU. Marginal structural Cox model was used to assess the relationship between receipt of sodium bicarbonate and hospital mortality, allowing pH, PaCO2, creatinine, and bicarbonate concentration as time-varying predictors of sodium bicarbonate exposure while adjusting for baseline characteristics of age, gender, Sequential Organ Failure Assessment score, acute kidney injury stage, Elixhauser score, quick Sequential Organ Failure Assessment, and Simplified Acute Physiology Score II. Setting: A large U.S.-based critical care database named Medical Information Mart for Intensive Care. Patients: Patients with Kidney Disease: Improving Global Outcomes acute kidney injury stage greater than or equal to 1 (> 1.5 × baseline creatinine) and one measurement of acidosis (pH ≤ 7.2). Baseline creatinine was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Interventions: None. Measurements and Main Results: Of the 3,406 eligible patients, 836 (24.5%) had received sodium bicarbonate treatment. Patients who received sodium bicarbonate treatment had a higher Sequential Organ Failure Assessment (9 vs 7; p < 0.001), lower pH (7.16 vs 7.18; p < 0.001), and bicarbonate concentration (16.51 ± 7.04 vs 20.57 ± 6.29 mmol/L; p < 0.001) compared with those who did not receive sodium bicarbonate. In the marginal structural Cox model by weighing observations with inverse probability of receiving sodium bicarbonate, sodium bicarbonate treatment was not associated with mortality in the overall population (hazard ratio, 1.16; 95% CI, 0.98–1.42; p = 0.132), but it appeared to be beneficial in subgroups of pancreatitis (hazard ratio, 0.53; 95% CI, 0.28–0.98; p = 0.044) and severe acidosis (pH < 7.15; hazard ratio, 0.75; 95% CI, 0.58–0.96; p = 0.024). Furthermore, sodium bicarbonate appeared to be beneficial in patients with severe bicarbonate deficit (< –50 kg·mmol/L). Conclusions: In the analysis by adjusting for potential confounders, there is no evidence that IV sodium bicarbonate is beneficial for patients with acute kidney injury and acidosis. Although the study suggested potential beneficial effects in some highly selected subgroups, the results need to be validated in experimental trials. Dr. Zhang conceived the study idea and design, drafted the manuscript, and obtained funding. Mr. Mo performed acquisition of data. Drs. Zhang and Ho performed analysis and interpretation of data. Dr. Ho performed critical revision of the manuscript for important intellectual content and statistical analysis. Dr. Hong took administrative, technical, or material support tasks. 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. Zhang received funding from the public welfare research project of Zhejiang province (LGF18H150005) and Scientific research project of Zhejiang Education Commission (Y201737841). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail Zhongheng Zhang at: zh_zhang1984@zju.edu.cn Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

A Core Outcome Set for Critical Care Ventilation Trials Objectives: Our objective was to obtain international consensus on a set of core outcome measures that should be recorded in all clinical trials of interventions intended to modify the duration of ventilation for invasively mechanically ventilated patients in the ICU. Design: A two-stage consensus process was undertaken between December 2015 and January 2018. Stage 1 included an online three-round Delphi study and three consensus meetings. Stage 2 included three consensus meetings. Setting: The setting was international, including Europe, North and South America, Australia, Asia, and Africa. Participants: Organization members representing intensive care survivors and carers; nursing, allied health professionals, and critical care physicians; clinical trials groups and trial investigators; and industry. Interventions: None. Measurements and Main Results: Delphi study outcomes were scored by participants from one (least important) to nine (most important). Consensus criteria for including the outcome in the core set were more than 70% of responses rating the outcome above seven and not more than 15% rating the outcome less than 3. From 222 participants, 183 from 38 organizations in 27 countries contributed to the consensus process. Stage 1: Delphi response rates from 200 participants ranged from 89% to 90% across three rounds. Forty-seven outcomes were ranked as follows: 19 met consensus criteria for inclusion and were considered at three consensus meetings (33 participants). Six outcomes were agreed for the core set as follows: extubation, reintubation, duration of mechanical ventilation, length of stay, health-related quality of life, and mortality. Stage 2: Three consensus meetings (37 participants) agreed on the measures for each outcome. Conclusions: We used rigorous and well-established methods to develop a core outcome set for use in all clinical trials evaluating interventions intended to modify duration of mechanical ventilation. This core outcome set will inform the design of future trials in this field by strengthening methodological quality and improving comparability across trials. This work was performed at the Queen’s University Belfast. All authors substantially contributed to the conception and design of the study; the analysis; interpretation of the data; drafting the work and revising it critically for important intellectual content. All authors provided final approval of the version to be published and agree to be accountable for all aspects of the work. 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 Department of Education and Learning (Northern Ireland) through a funded PhD studentship for Dr. Ringrow. Dr. Ringrow’s institution received funding from Northern Ireland Department for the Economy Doctoral Fellowship. Dr. McAuley received funding from Bayer, GlaxoSmithKline, and Boehringer Ingelheim. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Bronagh Blackwood, RN, PhD, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, Wellcome-Wolfson Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom. E-mail: b.blackwood@qub.ac.uk 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.

Lactated Ringer’s Versus 4% Albumin on Lactated Ringer’s in Early Sepsis Therapy in Cancer Patients: A Pilot Single-Center Randomized Trial Objective: To investigate the effects of the administration of 4% albumin on lactated Ringer’s, when compared with lactated Ringer’s alone, in the early phase of sepsis in cancer patients. Design: Single-center, randomized, double-blind, controlled-parallel trial. Setting: A tertiary care university cancer hospital. Patients: Cancer patients with severe sepsis or septic shock. Interventions: Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer’s solution or lactated Ringer’s solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay. Measurements and Main Results: A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer’s group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer’s group (p = 0.2). No significant differences in secondary outcomes were observed. Conclusions: Adding albumin to early standard resuscitation with lactated Ringer’s in cancer patients with sepsis did not improve 7-day survival. 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 departmental funds only. Dr. Martin received funding from Grifols. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the Cancer Institute of the University of Sao Paulo, Sao Paulo, Brazil. For information regarding this article, E-mail: landoni.giovanni@hsr.it Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Discharge Destination As a Marker of Mobility Impairment in Survivors of Acute Respiratory Distress Syndrome Objectives: Discharge destination is a commonly used surrogate for long-term recovery in rehabilitation studies. We determined the accuracy of discharge destination as a surrogate marker for 6-month mobility impairment in acute respiratory distress syndrome survivors. Design/Setting: Secondary analysis of the Economic Analysis of Pulmonary Artery Catheters study, a long-term observational sub-study of the National Institutes of Health/National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial. Patients: Patients underwent functional assessment using the Health Utilities Index-2 mobility domains at 6 months. A score greater than or equal to 3 (i.e., need for assistive device) defined mobility impairment. Discharge to any institutional care constituted a care facility discharge. We used logistic regression to explore the association between discharge destination and mobility impairment. We generated test characteristics and receiver operating characteristics to assess the accuracy of discharge destination as a surrogate for mobility impairment. Interventions: None. Measurements and Main Results: A total of 591 patients were enrolled in Economic Analysis of Pulmonary Artery Catheters in whom 328 had functional measurements at 6 months with 116 (35%) of these patients discharged to a care facility. Care facility patients were older (mean age 53 vs 44 yr; p < 0.001) and had longer hospital durations (length of stay 29 vs 17 d; p < 0.001). Care facility discharge was associated with greater 6-month mobility impairment. Sensitivity and specificity of discharge to a care facility for mobility impairment were 40.5% (95% CI, 32.0–49.6%) and 79.3% (95% CI, 73.3–84.2%) at 6 months. Discharge destination alone was a poor discriminator of long-term mobility impairment (receiver operating characteristic area under the curve: 0.61 at 6 mo). Conclusions: Discharge to a care facility was strongly associated with mobility impairment 6 months after acute respiratory distress syndrome but discharge destination alone performed poorly as a surrogate for mobility impairment. This work was completed at Louisiana State University Health Sciences Center, New Orleans, LA, and data were collected for the study at the University of Pittsburgh, Pittsburgh, PA. Dr. Jolley performed this data analysis. Dr. Angus and Clermont were responsible for acquisition of the original Economic Analysis of Pulmonary Artery Catheters data. Drs. Angus, Clermont, and Hough, contributed to data interpretation and drafting of the article. All authors contributed to the study design. Supported, in part, by grant from the National Institutes of Health/National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. Dr. Jolley is supported in part by 1 U54 GM104940 from the National Institute of General Medical Sciences which funds the Louisiana Clinical and Translational Science Center and the National Institute of Alcohol Abuse and Alcoholism (1K23AA026315-01A1). Dr. Clermont received funding from the National Institutes of Health (NIH) and the National Science Foundation. Dr. Jolley, Clermont, and Hough received support for article research from the NIH. Dr. Angus has disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Sarah Jolley, MD, MSc, Section of Pulmonary/Critical Care Medicine and Allergy/Immunology, 1901 Perdido Street, Suite 3205, New Orleans, LA 70112. E-mail: sjolle@lsuhsc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Epidemiology and Outcomes of Cancer-Related Versus Non–Cancer-Related Sepsis Hospitalizations Objective: Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non–cancer-related sepsis. Design: Observational cohort. Setting: National Readmissions Database (2013–2014), containing all-payer claims for 49% of U.S. population. Patients: A total of 1,104,363 sepsis hospitalizations. Interventions: We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non–cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non–cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses. Measurements and Main Results: There were 27,481,517 hospitalizations in National Readmissions Database 2013–2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non–cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non–cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non–cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non–cancer-related sepsis (p < 0.001). Conclusions: In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. 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 K08 GM115859 (to Dr. Prescott) and K12 HL138039 (to Dr. Donnelly) from the National Institutes of Health. Dr. Donnelly’s institution received funding from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute. Drs. Donnelly and Prescott received support for article research from the NIH. Dr. Prescott’s institution received funding from the NIH, and she disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: hematthe@med.umich.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Optimal Arterial Blood Oxygen Tension in the Early Postresuscitation Phase of Extracorporeal Cardiopulmonary Resuscitation: A 15-Year Retrospective Observational Study Objectives: Hyperoxia could lead to a worse outcome after cardiac arrest. Few studies have investigated the impact of oxygenation status on patient outcomes following extracorporeal cardiopulmonary resuscitation. We sought to delineate the association between oxygenation status and neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. Design: Retrospective analysis of a prospective extracorporeal cardiopulmonary resuscitation registry database. Setting: An academic tertiary care hospital. Patients: Patients receiving extracorporeal cardiopulmonary resuscitation between 2000 and 2014. Interventions: None. Measurements and Main Results: A total of 291 patients were included, and 80.1% were male. Their mean age was 56.0 years. The arterial blood gas data employed in the primary analysis were recorded from the first sample over the first 24 hours in the ICUs after return of spontaneous circulation. The mean PaO2 after initiation of venoarterial extracorporeal membrane oxygenation was 178.0 mm Hg, and the mean PaO2/FIO2 ratio was 322.0. Only 88 patients (30.2%) demonstrated favorable neurologic status at hospital discharge. Multivariate logistic regression analysis indicated that PaO2 between 77 and 220 mm Hg (odds ratio, 2.29; 95% CI, 1.01–5.22; p = 0.05) and PaO2/FIO2 ratio between 314 and 788 (odds ratio, 5.09; 95% CI, 2.13–12.14; p < 0.001) were both positively associated with favorable neurologic outcomes. Conclusions: Oxygenation status during extracorporeal membrane oxygenation affects neurologic outcomes in patients receiving extracorporeal cardiopulmonary resuscitation. The PaO2 range of 77 to 220 mm Hg, which is slightly narrower than previously defined, seems optimal. The PaO2/FIO2 ratio was also associated with outcomes in our analysis, indicating that both PaO2 and the PaO2/FIO2 ratio should be closely monitored during the early postcardiac arrest phase for postextracorporeal cardiopulmonary resuscitation patients. Drs. W.-J. Chen and Y.-S. Chen contributed equally to this work. 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 authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Yih-Sharng Chen, MD, PhD, Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100, Taiwan. E-mail: yschen1234@gmail.com; Wen-Jone Chen, MD, PhD, Department of Emergency Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist., Taipei City 100, Taiwan. E-mail: wjchen1955@ntu.edu.tw Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.