Cell Cycle Biomarkers and Soluble Urokinase-Type Plasminogen Activator Receptor for the Prediction of Sepsis-Induced Acute Kidney Injury Requiring Renal Replacement Therapy: A Prospective, Exploratory Study Objectives: Sepsis-induced acute kidney injury is the dominant acute kidney injury etiology in critically ill patients and is often associated with a need for renal replacement therapy. The indication and timing of renal replacement therapy are controversially discussed. We hypothesized that the product of the G1-cell cycle arrest biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), and the soluble urokinase-type plasminogen activator receptor are of diagnostic value for the prediction of septic acute kidney injury courses requiring renal replacement therapy. Design: In this prospective study, critically ill patients were enrolled immediately after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2] × [IGFBP7] levels over time and serum soluble urokinase-type plasminogen activator receptor levels once at inclusion were measured. The primary endpoint was the development of septic acute kidney injury with the need for renal replacement therapy. Area under the receiver operating characteristic curves, de Long’s tests, and logistic regression models were calculated. Setting: Two ICUs at Heidelberg University Hospital between May 2017 and July 2018. Patients: One-hundred critically ill patients with positive Sepsis-3 criteria. Interventions: None. Measurement and Main Results: Nineteen patients required renal replacement therapy. Diagnostic performance of urinary [TIMP-2] × [IGFBP7] improved over time with the highest area under the receiver operating characteristic curve of 0.89 (95% CI, 0.80–0.98) 24 hours after study inclusion. Soluble urokinase-type plasminogen activator receptor levels at inclusion showed an area under the receiver operating characteristic curve of 0.83 (0.75–0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2] × [IGFBP7] at 24 hours after inclusion by applying a cutoff value of greater than or equal to 0.6 (ng/mL)2/1,000 (sensitivity 90.9, specificity 67.1). Soluble urokinase-type plasminogen activator receptor performed best by using a cutoff value of greater than or equal to 8.53 ng/mL (sensitivity 84.2, specificity 82.7). A combination of newly tested biomarkers with cystatin C resulted in a significantly improved diagnostic accuracy. Cystatin C in combination with [TIMP-2] × [IGFBP7] 24 hours outperformed all standard renal parameters (area under the receiver operating characteristic curve 0.93 [0.86–1.00]). Conclusions: [TIMP-2] × [IGFBP7] and soluble urokinase-type plasminogen activator receptor are promising biomarker candidates for the risk stratification of septic acute kidney injury patients with the need for renal replacement therapy. 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. Nusshag disclosed that he is funded by the Physician Scientist Programme of Heidelberg Faculty of Medicine. Dr. Reiser received funding from the National Institutes of Health (NIH) (grants), Massachusetts General Hospital (consulting), UptoDate (consulting), TRISAQ (equity/stock owner), NEPHCURE (grant), Thermo BCT (grant), Genentech (consulting), Merck (consulting), and Inceptionsci (consulting), and he received support for article research from the NIH. Dr. Brenner received funding from the German Research Foundation and the Heidelberg Foundation of Surgery. Moreover, he received honoraria for lectures from Biotest AG, Baxter Germany GmbH, Schöchl medical education GmbH, Boehringer Ingelheim Pharma GmbH, CSL Behring GmbH, Astellas Pharma GmbH, B. Braun Melsungen AG, and Merck Sharp & Dohme GmbH. He also disclosed that he is an advisory board member of Baxter Germany GmbH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Christian.Nusshag@med.uni-heidelberg.de 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.

Incidence and Outcomes of Sepsis in Korea: A Nationwide Cohort Study From 2007 to 2016 Objectives: This study aimed to estimate the incidence and clinical outcomes of sepsis in Korea from 2007 to 2016. Design: Retrospective observational study. Setting: Nationwide study with population-based healthcare reimbursement claims database. Patients: Using data from the National Health Insurance Service of Korea, patients who were hospitalized with a diagnosis of sepsis from 2007 to 2016 were analyzed. The incidence of sepsis was calculated using mid-year census population and analyzed according to year, age, and sex. The Elixhauser Comorbidity Index score was calculated to adjust for the impact of comorbidities on clinical outcome. In-hospital mortality, hospital length of stay, ICU admission rates, and risk factors for in-hospital mortality were also analyzed. Interventions: None. Measurements and Main Results: The incidence of sepsis increased from 173.8 per 100,000 population in 2007 to 233.6 per 100,000 population in 2016. In-hospital mortality decreased from 30.9% in 2007 to 22.6% in 2016 (p < 0.0001). From 2007 to 2016, hospital length of stay and ICU admission rates associated with sepsis decreased from 26.0 ± 33.5 days to 21.3 ± 24.4 days (p < 0.0001) and from 16.2% to 12.7% (p < 0.0001), respectively. Male sex, age greater than 50 years, Elixhauser Comorbidity Index greater than 10, and mechanical ventilation were identified as risk factors for in-hospital mortality after adjusting for baseline characteristics. Conclusions: The incidence of sepsis in Korea increased from 2007 to 2016, while the associated in-hospital mortality, hospital length of stay, and ICU admission rates decreased. Dr. Ryu is the guarantor of the content of the article. Dr. Oh contributed substantially to the study design, data interpretation, and the writing of the first draft and subsequent revisions of the article. Dr. Cho, Ms. Kim, and Drs. Jang, Choi, and Lee contributed substantially to data analysis and interpretation, and the writing of the article. Dr. Ryu has contributed substantially to the study design, data analysis and interpretation, and the writing of the first draft and subsequent 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). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: hogeol@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

A Prospective Analysis of Motor and Cognitive Skill Retention in Novice Learners of Point of Care Ultrasound Objectives: To identify the time at which point of care ultrasound static image recognition and image acquisition skills decay in novice learners. Setting: The University of Iowa Hospitals and Clinics. Subjects: Twenty-four subjects (23 first-year medical students and one first-year physician assistant student). Design: The subjects completed an initial didactic and hands-on session with immediate testing of learned image acquisition and static image identification skills. Interventions: Retesting occurred at 1, 4, and 8 weeks after the initial training session with no retraining in between. Image acquisition skills were obtained on the same healthy male volunteers, and the students were given no immediate feedback on their performance. The image identification skills were assessed with a 10 question test at each follow-up session. Measurements and Main Results: For pleural ultrasound by 4 weeks, there was a significant decline of the ability to identify A-lines (p = 0.0065). For pleural image acquisition, there was no significant decline in the ability to demonstrate lung sliding. Conversely, cardiac image recognition did not significantly decline throughout the study, while the ability to demonstrate cardiac images at 4 weeks (parasternal short axis view) did (p = 0.0008). Conclusions: Motor and cognitive skills decay at different times for pleural and cardiac images. Future ultrasound curricula should retrain skills at a maximum of 8 weeks from initial training. They should focus more on didactic sessions related to image identification for pleural images, and more hands-on image acquisition training for cardiac images, which represents a novel finding. 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, departmental funds from the Department of Internal Medicine. Dr. Schmidt received funding from McGraw-Hill, UpToDate, and Springer Science. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: charles-rappaport@uiowa.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study Objectives: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. Design: Ancillary investigation of a prospective observational study. Setting: Twenty-one ICUs with 1-year follow-up. Patients: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. Interventions: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. Measurements and Main Results: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25–47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). Conclusions: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge. The complete list of French and euRopean Outcome reGistry in ICUs (FROG-ICU) Investigators is: Etienne Gayat, Alain Cariou, Nicolas Deye, Antoine Vieillard-Baron, Samir Jaber, Charles Damoisel, Qin Lu, Xavier Monnet, Isabelle Rennuit, Elie Azoulay, Marc Léone, Heikel Oueslati, Bertrand Guidet, Diane Friedman, Antoine Tesnière, Romain Sonneville, Philippe Montravers, Sébastien Pili-Floury, Jean-Yves Lefrant, Jacques Duranteau, Pierre-François Laterre, Nicolas Brechot, Karine Chevreul, Morgane Michel, Bernard Cholley, Matthieu Legrand, Jean-Marie Launay, Eric Vicaut, Mervyn Singer, Matthieu Resche-Rigon, and Alexandre Mebazaa. This work was performed at Hôpital Lariboisière, Paris, France; Hôpital Saint-Louis, Paris, France; Hôpital Bichat, Paris, France; Hôpital Beaujon, Paris, France; Hôpital Cochin, Paris, France; Hôpital Bicêtre, Le Kremlin Bicêtre, France; Hôpital Raymond Poincaré, Garches, France; Hôpital Saint-Antoine, Paris, France; Hôpital Nord, Marseille, France; Hôpital de la Pitié-Salpêtrière, Paris, France; Hôpital Saint-Eloi, Montpellier, France; Hôpital Ambroise Paré, Boulogne, France; Hôpital Caremeau, Nîmes, France; Hôpital Jean Minjoz, Besançon, France; Hôpital Saint-Luc, Bruxelles, Belgique. 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). French and euRopean Outcome reGistry in ICU (ClinicalTrials.gov Identifier NCT01367093) was funded by the Programme Hospitalier de la Recherche Clinique (AON 10-216) and by a research grant from the Société Française d’Anesthésie Réanimation. Abbott, Sphingotec, Roche Diagnostics, and Critical Diagnostics provided unrestricted free kits to Assistance Publique-Hôpitaux de Paris to conduct biomarker analyses. Dr. Legrand disclosed French and euRopean Outcome reGistry in ICU (ClinicalTrials.gov Identifier NCT01367093) was funded by the Programme Hospitalier de la Recherche Clinique (AON 10-216) and by a research grant from the Société Française d’Anesthésie Réanimation; he received lecture fees from Alere, Fresenius, and Gilead and Consulting fees from Adrenomed. Dr. Deye’s institution received funding from Zoll and Bard for travel and lecture fees. Dr. Fournier’s institution received funding from Programme Hospitalier de la Recherche Clinique (AON 10-216) and a research grant from the Société Française d’Anesthésie Réanimation. Dr. Monnet received funding from Pulsion Medical Systems, and he received support for article research from Assistance publique hôpitaux de Paris. Dr. Darmon received consulting fees from Sanofi and Gilead-Kite, research support from Astute Medical and Merck Sharp & Dohme, (MSD), and speaker fees from MSD, Gilead-Kite, and Astellas. Dr. Zafrani received funding from Jazz Pharmaceuticals (research grant). Dr. Leone received funding from MSD, Pfizer, Amomed, Aguettant (consulting), Octapharma (lecture), Aspen (lecture), and Orion (lecture). Dr. Pili-Floury received funding from Pfizer. Dr. Sato disclosed work for hire. Dr. Mebazaa has received speaker’s honoraria from Novartis, Orion, Servier, and fee as member of advisory board and/or Steering Committee from Cardiorentis, Adrenomed, Sphingotec, Sanofi, Roche, Abbott, and Bristol-Myers Squibb. Dr. Gayat’s institution received funding from programme hospitalier de recherche clinique 2011, Retia Medical, and Société Française d’Anesthésie Réanimation; he received funding from Adrenomed, Roche Diagnostics and Magnisense, lecture fees from Edwards LifeScience. The remaining authors have disclosed that they do not have any potential conflicts of interest. Trial registration: ClinicalTrials.gov NCT01367093; registered on June 6, 2011. For information regarding this article, E-mail: matthieu.legrand@aphp.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Toward Increased Understanding of the Steroid Controversy in Septic Shock No abstract available

Promoting Family Engagement in the ICU: Experience From a National Collaborative of 63 ICUs Objectives: As part of an improvement program targeting ICU, a national collaborative was launched to help hospitals implement patient- and family-centered care engagement initiatives. Design: Ten-month quality improvement collaborative. Setting: Guided by a national patient and family advisory group, participating teams implemented an individual project including open visitation; integrating families on rounds; establishing a patient and family advisory committee; using patient and family diaries, among others. Subjects: Sixty-three adult and PICU teams from both academic and community hospitals in 34 states participated. Interventions: Monthly team calls, quarterly webinars, newsletters, an online eCommunity, and team reporting assignments were used to facilitate project implementation. Measurements and Main Results: The Family Satisfaction with Care in the ICU 24 was used to assess family satisfaction. Clinician perceptions were assessed with the Institute for Patient- and Family-Centered Care Self-Assessment Inventory. Thematic analysis was used to explore narrative data captured from team reports of project barriers, facilitators, and the experience of participating in the collaborative. A total of 2,530 family member and 3,999 clinician surveys were completed. Postimplementation, family members reported statistically significant increases in overall family satisfaction, satisfaction with decision-making, and satisfaction with quality of care (Family Satisfaction with Care in the ICU mean score change range 0.83–1.24; p ≤ 0.027). Clinicians reported that opportunities for families to participate as members of the care team increased. Major barriers included lack of buy-in and ability to promote change in the clinical setting, managing the workload of implementation, and funding to support initiatives. Conclusions: A national collaborative format was useful to assist ICU teams to implement patient- and family-engagement initiatives. Enlisting stakeholder support, engaging unit-based champions, and highlighting benefits of family engagement can help ICU teams to promote family member involvement and engagement. 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 disclosed that this article reports on the work of a Patient-Centered Outcomes Research Institute (PCORI) Eugene Washington PCORI Engagement Award (6262-SCCM), and disclosed that she served as Society of Critical Care Medicine (SCCM) President-Elect and President during the time of the project. Drs. Kleinpell and Ms. Harmon received support for article research from PCORI. Dr. Zimmerman’s institution received funding from the National Institutes of Health and Immunexpress (research funding), and he received funding from Elsevier Publishing (royalties for co-editing Pediatric Critical Care) and SCCM (travel reimbursement to attend board meetings). Ms. Harmon’s institution received funding from PCORI. Mr. Hanson received funding from Eugene Washington PCORI Engagement Award for the “Improving Care for Critically Ill Patients and Families Through Research Dissemination and Implementation” SCCM Collaborative. Dr. Hwang received funding from SCCM. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Ruth Kleinpell, PhD, RN, Vanderbilt University School of Nursing, 461 21st Avenue South 407 GH, Nashville, TN 37240. E-mail: ruth.kleinpell@vanderbilt.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Racial and Ethnic Disparities in Postcardiac Arrest Targeted Temperature Management Outcomes Objectives: To evaluate racial and ethnic disparities in postcardiac arrest outcomes in patients undergoing targeted temperature management. Design: Retrospective study. Setting: ICUs in a single tertiary care hospital. Patients: Three-hundred sixty-seven patients undergoing postcardiac arrest targeted temperature management, including continuous electroencephalogram monitoring. Interventions: None. Measurements and Main Results: Clinical variables examined in our clinical cohort included race/ethnicity, age, time to return of spontaneous circulation, cardiac rhythm at time of arrest, insurance status, Charlson Comorbidity Index, and time to withdrawal of life-sustaining therapy. CT at admission and continuous electroencephalogram monitoring during the first 24 hours were used as markers of early injury. Outcome was assessed as good (Cerebral Performance Category 1–2) versus poor (Cerebral Performance Category 3–5) at hospital discharge. White non-Hispanic (“White”) patients were more likely to have good outcomes than white Hispanic/nonwhite (“Non-white”) patients (34.4 vs 21.7%; p = 0.015). In a multivariate model that included age, time to return of spontaneous circulation, initial rhythm, combined electroencephalogram/CT findings, Charlson Comorbidity Index, and insurance status, race/ethnicity was still independently associated with poor outcome (odds ratio, 3.32; p = 0.003). Comorbidities were lower in white patients but did not fully explain outcomes differences. Nonwhite patients were more likely to exhibit signs of early severe anoxic changes on CT or electroencephalogram, higher creatinine levels and receive dialysis, but had longer duration to withdrawal of lifesustaining therapy. There was no significant difference in catheterizations or MRI scans. Subgroup analysis performed with patients without early electroencephalogram or CT changes still revealed better outcome in white patients. Conclusions: Racial/ethnic disparity in outcome persists despite a strictly protocoled targeted temperature management. Nonwhite patients are more likely to arrive with more severe anoxic brain injury, but this does not account for all the disparity. This work was performed at Brigham and Women’s Hospital. Dr. Jacobs contributed to acquisition of data, analysis of the data, and drafting the article. Mr. Beers and Ms. Park contributed to acquisition of data. Drs. Scirica and Hsu contributed to acquisition of data and revising the article for intellectual content. Dr. Henderson contributed to revising the article for intellectual content. Dr. Bevers contributed to analysis of the data and revising the article for intellectual content. Dr. Dworetzky contributed to analysis of the data and writing of the article. Dr. Lee contributed to design of the study, acquisition of data, analysis of the data, and drafting the article. Dr. Jacobs is partially supported (80%) by the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) R25NS065743, principal investigator (PI), 2017–2019 (ongoing), she performs contract work (electroencephalogram [EEG] reading) for Carle Foundation Hospital, and she disclosed that she is an inventor on two (unlicensed) patents relating to work she performed during graduate school (United States Patent US 7,935,530 B2. November 28, 2007; United States Patent US 9,630,950. April 25, 2017); she has not received any compensation related to these patents. Drs. Jacobs and Lee received support for article research from the NIH. Ms. Park disclosed work for hire. Dr. Scirica received research grants via Brigham and Women’s Hospital from AstraZeneca, Eisai, Novartis, and Merck, and he has received consulting fees from AbbVie, Allergan, AstraZeneca, Boehringer Ingelheim, Covance, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Medtronic, Merck, NovoNordisk, Sanofi, and equity in Health [at] Scale, outside the submitted work. Dr. Bevers receives research support from the American Academy of Neurology and David Heitman Neurovascular Research Fund (unrelated to the current work), outside the scope of the submitted work; he reports grants and personal fees from Biogen and EBSCO Health, outside the scope of the submitted work; and he reports personal fees for editorial work from Dynamed, LCC, outside the scope of the submitted work. Dr. Dworetzky reads EEGs in her clinical practice (25% effort) and bills for this, performs contract work with SleepMed/DigiTrace, is a consultant for SleepMed (EEG interpretation) and for Best Doctors (clinical consults) & Oxford University Press (royalties). Dr. Lee reads EEGs in his clinical practice (25% effort) and bills for this, performs contract work with SleepMed/DigiTrace and Advance Medical; he was supported by the NIH (NINDS R03NS091864 02, PI, 2015–2018). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jlee38@bwh.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Outcomes in Critically Ill Patients With Traumatic Brain Injury: Ethnicity, Documentation, and Insurance Status Objectives: Disparities in traumatic brain injury outcomes for ethnic minorities and the uninsured have previously been demonstrated; however, outcomes in undocumented immigrants have not been examined. We wanted to determine whether ethnicity, insurance, and documentation status served as risk factors for disparities in traumatic brain injury outcomes between undocumented immigrants and documented residents. Design: Retrospective study. Setting: Patients diagnosed with traumatic brain injury admitted to the surgical/trauma ICU at a level 1 trauma center serving a large immigrant population in New York City from 2009 to 2016. Patients: Four-hundred seventy-one traumatic brain injury patients requiring surgical/trauma ICU admission. Interventions: None. Measurements and Main Results: Undocumented immigrants constituted 29% of the population, were younger (39 vs 57 yr old, respectively; p < 0.0001), Hispanic (83%; p < 0.0001), and uninsured (87%; p < 0.0001). Falls resulted in the majority of traumatic brain injuries in the total population, however, undocumented immigrants were almost twice as likely to be assaulted (p = 0.0032). There was no difference in presence of midline shifts, Injury Severity Score, Glasgow Coma Score, hypotension, hypoxia, and pupillary reactions between undocumented immigrants and documented residents. Undocumented immigrants presented with significantly more effaced basilar cisterns (p = 0.0008). There was no difference in hospital care between undocumented immigrants and documented residents as determined by emergency department to surgical/trauma ICU transfer times (p = 0.967). Undocumented immigrants were more likely to be discharged home (53% vs 33%, respectively; p = 0.0009) and less likely to be sent to rehabilitation (25% vs 32%, respectively; p = 0.0009). After adjusting length of stay and mortality for covariates, undocumented immigrants had shorter length of stay (p < 0.05) and there was no difference in hospital mortality between undocumented immigrants and documented residents. Conclusions: Undocumented immigrants with traumatic brain injuries were more likely to be younger, have shorter length of stay, and experience similar mortality rates to documented residents. Social economic status may play a role in events prior to hospitalization and likely does in disposition outcomes. All work was performed at Elmhurst Hospital Center. The authors have disclosed that they do not have any potential conflicts of interest. Presented, in part, preliminary data at the Society of Critical Care Medicine 47th Critical Care Congress, San Antonio, TX, February 26, 2018. For information regarding this article, E-mail: coritsg@nychhc.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Hyperosmolar Therapy in Pediatric Severe Traumatic Brain Injury—A Systematic Review Objectives: Traumatic brain injury is a leading cause of hospital visits for children. Hyperosmolar therapy is often used to treat severe traumatic brain injury. Hypertonic saline is used predominantly, yet there remains disagreement about whether hypertonic saline or mannitol is more effective. Data Sources: Literature search was conducted using Pubmed, Cochrane, and Embase. Systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study Selection: Retrospective and prospective studies assessing use of hyperosmolar therapy in pediatric patients with severe traumatic brain injury were included. Data Extraction: Two independent authors performed article review. Two-thousand two-hundred thirty unique articles were initially evaluated, 11 were included in the final analysis, with a total of 358 patients. Study quality was assessed using Modified Newcastle-Ottawa Scale and Jadad score. Data Synthesis: Of the 11 studies, all evaluated hypertonic saline and four evaluated both hypertonic saline and mannitol. Nine reported that hypertonic saline lowered intracranial pressure and two reported that mannitol lowered intracranial pressure. The studies varied significantly in dose, concentration, and administrations schedule for both hypertonic saline and mannitol. Five studies were prospective, but only one directly compared mannitol to hypertonic saline. The prospective comparison study found no difference in physiologic outcomes. Clinical outcomes were reported using different measures across studies. For hypertonic saline-treated patients, mechanical ventilation was required for 6.9–9 days, decompressive craniectomy was required for 6.25–29.3% of patients, ICU length of stay was 8.0–10.6 days, in-hospital mortality was 10–48%, and 6-month mortality was 7–17%. In mannitol-treated patients, ICU length of stay was 9.5 days, in-hospital mortality was 56%, and 6-month mortality was 19%. Conclusions: Both hypertonic saline and mannitol appear to lower intracranial pressure and improve clinical outcomes in pediatric severe traumatic brain injury, but the evidence is extremely fractured both in the method of treatment and in the evaluation of outcomes. Given the paucity of high-quality data, it is difficult to definitively conclude which agent is better or what treatment protocol to follow. Ms. Stopa and Ms. Dolmans contributed equally and shared first authorship. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sizzy@partners.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Pro: Selective Digestive Decontamination Is Neither Safe Nor Efficacious for Critically Ill Patients No abstract available