Critical Care Medicine

Impact on Patient Outcomes of Pharmacist Participation in Multidisciplinary Critical Care Teams: A Systematic Review and Meta-Analysis Objectives: The objective of this systematic review and meta-analysis was to assess the effects of including critical care pharmacists in multidisciplinary ICU teams on clinical outcomes including mortality, ICU length of stay, and adverse drug events. Data Sources: PubMed, EMBASE, and references from previous relevant systematic studies. Study Selection: We included randomized controlled trials and nonrandomized studies that reported clinical outcomes such as mortality, ICU length of stay, and adverse drug events in groups with and without critical care pharmacist interventions. Data Extraction: We extracted study details, patient characteristics, and clinical outcomes. Data Synthesis: From the 4,725 articles identified as potentially eligible, 14 were included in the analysis. Intervention of critical care pharmacists as part of the multidisciplinary ICU team care was significantly associated with the reduced likelihood of mortality (odds ratio, 0.78; 95% CI, 0.73–0.83; p < 0.00001) compared with no intervention. The mean difference in ICU length of stay was –1.33 days (95% CI, –1.75 to –0.90 d; p < 0.00001) for mixed ICUs. The reduction of adverse drug event prevalence was also significantly associated with multidisciplinary team care involving pharmacist intervention (odds ratio for preventable and nonpreventable adverse drug events, 0.26; 95% CI, 0.15–0.44; p < 0.00001 and odds ratio, 0.47; 95% CI, 0.28–0.77; p = 0.003, respectively). Conclusions: Including critical care pharmacists in the multidisciplinary ICU team improved patient outcomes including mortality, ICU length of stay in mixed ICUs, and preventable/nonpreventable adverse drug events. Drs. Lee and Ryu contributed equally to this work as co-first authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by the Korean Hospital Pharmaceutical Education & Research Center (No. KSHPERC-18-01). The authors have disclosed that they have no potential conflicts of interest. For information regarding this article, E-mail: eykimjcb777@cau.ac.kr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Adjusting for Disease Severity Across ICUs in Multicenter Studies Objectives: To compare methods to adjust for confounding by disease severity during multicenter intervention studies in ICU, when different disease severity measures are collected across centers. Design: In silico simulation study using national registry data. Setting: Twenty mixed ICUs in The Netherlands. Subjects: Fifty-five–thousand six-hundred fifty-five ICU admissions between January 1, 2011, and January 1, 2016. Interventions: None. Measurements and Main Results: To mimic an intervention study with confounding, a fictitious treatment variable was simulated whose effect on the outcome was confounded by Acute Physiology and Chronic Health Evaluation IV predicted mortality (a common measure for disease severity). Diverse, realistic scenarios were investigated where the availability of disease severity measures (i.e., Acute Physiology and Chronic Health Evaluation IV, Acute Physiology and Chronic Health Evaluation II, and Simplified Acute Physiology Score II scores) varied across centers. For each scenario, eight different methods to adjust for confounding were used to obtain an estimate of the (fictitious) treatment effect. These were compared in terms of relative (%) and absolute (odds ratio) bias to a reference scenario where the treatment effect was estimated following correction for the Acute Physiology and Chronic Health Evaluation IV scores from all centers. Complete neglect of differences in disease severity measures across centers resulted in bias ranging from 10.2% to 173.6% across scenarios, and no commonly used methodology—such as two-stage modeling or score standardization—was able to effectively eliminate bias. In scenarios where some of the included centers had (only) Acute Physiology and Chronic Health Evaluation II or Simplified Acute Physiology Score II available (and not Acute Physiology and Chronic Health Evaluation IV), either restriction of the analysis to Acute Physiology and Chronic Health Evaluation IV centers alone or multiple imputation of Acute Physiology and Chronic Health Evaluation IV scores resulted in the least amount of relative bias (0.0% and 5.1% for Acute Physiology and Chronic Health Evaluation II, respectively, and 0.0% and 4.6% for Simplified Acute Physiology Score II, respectively). In scenarios where some centers used Acute Physiology and Chronic Health Evaluation II, regression calibration yielded low relative bias too (relative bias, 12.4%); this was not true if these same centers only had Simplified Acute Physiology Score II available (relative bias, 54.8%). Conclusions: When different disease severity measures are available across centers, the performance of various methods to control for confounding by disease severity may show important differences. When planning multicenter studies, researchers should make contingency plans to limit the use of or properly incorporate different disease measures across centers in the statistical analysis. 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. Dr. Brakenhoff and Dr. Plantinga 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). Dr. de Keizer institution received funding from National Intensive Care Evaluation foundation, during the conduct of the study (grants and advisory board member). Dr. Groenwold was supported financially by the Netherlands Organisation for Scientific Research (project 917.16.430). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: N.L.Plantinga@umcutrecht.nl Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Recommendation of New Medical Alarms Based on Audibility, Identifiability, and Detectability in a Randomized, Simulation-Based Study Objectives: Accurate and timely identification of existing audible medical alarms is not adequate in clinical settings. New alarms that are easily heard, quickly identifiable, and discernable from one another are indicated. The "auditory icons" (brief sounds that serve as metaphors for the events they represent) have been proposed as a replacement to the current international standard. The objective was to identify the best performing icons based on audibility and performance in a simulated clinical environment. Design: Three sets of icon alarms were designed using empirical methods. Subjects participated in a series of clinical simulation experiments that examined the audibility, identification accuracy, and response time of each of these icon alarms. A statistical model that combined the outcomes was used to rank the alarms in overall efficacy. We constructed the "best" and "worst" performing sets based on this ranking and prospectively validated these sets in a subsequent experiment with a new subject sample. Setting: Experiments were conducted in simulated ICU settings at the University of Miami. Subjects: Medical trainees were recruited from a convenience sample of nursing students and anesthesia residents at the institution. Interventions: In Experiment 1 (formative testing), subjects were exposed to one of the three sets of alarms; identical setting and instruments were used throughout. In Experiment 2 (summative testing), subjects were exposed to one of the two sets of alarms, assembled from the best and worst performing alarms from Experiment 1. Measurements and Main Results: For each alarm, we determined the minimum sound level to reach audibility threshold in the presence of background clinical noise, identification accuracy (percentage), and response time (seconds). We enrolled 123 medical trainees and professionals for participation (78 with < 6 yr of training). We identified the best performing icon alarms for each category, which matched or exceeded the other candidate alarms in identification accuracy and response time. Conclusions: We propose a set of eight auditory icon alarms that were selected through formative testing and validated through summative testing for adoption by relevant regulatory bodies and medical device manufacturers. This work was performed at the University of Miami. 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 Association for the Advancement of Medical Instrumentation. Drs. Bennett's, Dudaryk's, Edworthy's, and McNeer's institution received funding from Association for the Advancement of Medical Instrumentation. Dr. Crenshaw disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: mcneer@miami.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

A 360° Rotational Positioning Protocol of Organ Donors May Increase Lungs Available for Transplantation Objectives: To evaluate the improvement in lung donation and immediate lung function after the implementation of a 360° rotational positioning protocol within an organ procurement organization in the Midwest. Design: Retrospective observational study. Setting: The Midwest Transplant Network from 2005 to 2017. Rotational positioning of donors began in 2008. Subjects: Potential deceased lung donors. Interventions: A 360° rotational protocol. Presence of immediate lung function in recipients, change in PaO2:FIO2 ratio during donor management, initial and final PaO2:FIO2 ratio, and proportion of lungs donated were measured. Outcomes were compared between rotated and nonrotated donors. Measurements and Main Results: A total of 693 donors were analyzed. The proportion of lung donations increased by 10%. The difference between initial PaO2:FIO2 ratio and final PaO2:FIO2 ratio was significantly different between rotated and nonrotated donors (36 ± 116 vs 104 ± 148; p < 0.001). Lungs transplanted from rotated donors had better immediate function than those from nonrotated donors (99.5% vs 68%; p < 0.001). Conclusions: There was a statistically significant increase in lung donations after implementing rotational positioning of deceased donors. Rotational positioning significantly increased the average difference in PaO2:FIO2 ratios. There was also superior lung function in the rotated group. The authors recommend that organ procurement organizations consider adopting a rotational positioning protocol for donors to increase the lungs available for transplantation. 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). University of Missouri Kansas City and Midwest Transplant Network are sponsoring institutions. Dr. Whitt received funding from Midwest Transplant Network. Dr. Wilkins disclosed that he is the administrative Medical Director for, and is also a member of, Midwest Transplant Network. The remaining authors have disclosed that they do not have any potential conflicts of interest For information regarding this article, E-mail: mendezmar@umkc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Clinician Perception of a Machine Learning–Based Early Warning System Designed to Predict Severe Sepsis and Septic Shock Objective: To assess clinician perceptions of a machine learning–based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). Design: Prospective observational study. Setting: Tertiary teaching hospital in Philadelphia, PA. Patients: Non-ICU admissions November–December 2016. Interventions: During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert's helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. Measurements and Main Results: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient's risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. Conclusions: In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning–based sepsis alerts. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Ginestra, Dr. Schweickert, Ms. Meadows, Mr. Lynch, and Ms. Pavan helped with data collection; Dr. Ginestra helped with analysis and interpretation of the data, and drafting of the article; and all authors helped with conception and design, and critical revision of the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http;/journals.lww.com/ccmjournal). Dr. Umscheid's contribution to this project was supported, in part, by the National Center for Research Resources (grant no: UL1RR024134), which is now at the National Center for Advancing Translational Sciences (grant no: UL1TR000003). Presented as a poster at the 2017 Society of Hospital Medicine Annual Meeting, Las Vegas, NV. Dr. Schweickert has received funding from the American College of Physicians and Arjo. Dr. Umscheid's institution has received funding from the National Institutes of Health, Food and Drug Administration, and Agency for Healthcare Research and Quality Evidence-based Practice Center contracts, and he has received funding from the Patient-Centered Outcomes Research Institute Advisory Panel and Northwell Health (grand rounds honoraria). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Craig A. Umscheid, MD, MS, Office of Clinical Excellence, University of Chicago Medicine, American School Building, 850 E. 58th Street, Suite 123, Office 128, MC 1135, Chicago, IL 60637. E-mail: craigumscheid@medicine.bsd.uchicago.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Calorie Intake During Status Epilepticus and Outcome: A 5-Year Cohort Study Objectives: Recommendations regarding nutrition during status epilepticus are lacking, and it is unclear whether restriction of calorie intake would result in beneficial effects or potential harm. We thus aimed to investigate associations between daily calorie intake and outcome in adult status epilepticus patients deriving from a 5-year cohort with a systematic and prospective collection of nutritional data. Design: Retrospective observational study. Setting: Medical ICUs at a tertiary academic medical care center. Patients: Consecutive patients with status epilepticus treated at the ICUs from 2012 to 2016 were included. Interventions: None. Measurements and Main Results: All patients with status epilepticus were monitored regarding nutrition support provided according to the guidelines. Relative risks of no return to baseline were estimated by Poisson regression with robust error variance and adjusted for potential confounders. Of 203 patients, 86 (42%) had return to baseline. Metabolic characteristics of patients with and without return to baseline did not differ. Patients without return to baseline received more calories and proteins per status epilepticus day, and increasing nutritional support was associated with ventilator-associated pneumonia (relative risk, 1.19; 95% CI, 1.09–1.28). Multivariable regression analysis revealed significant increases in relative risks for no return to baseline with every percent of days with nutrition (relative risk, 1.35; 95% CI, 1.05–1.74), with every 100 kcal (relative risk, 1.01; 95% CI, 1.002–1.01), and gram of protein intake (relative risk, 1.01; 95% CI, 1.001–1.01) per status epilepticus day, independent of potential confounders (including fatal etiology, duration and severity of status epilepticus, Charlson comorbidity index, and treatment with anesthetics). Conclusions: Our results indicate that increased calorie intake during status epilepticus is independently associated with unfavorable outcome. These findings require further validation and investigations into potential mediators, such as induction of ketogenesis, immunomodulating effects, and/or reduction of ICU-associated complications, such as infections. Drs. Rybitschka and Sutter planned the work, acquired and interpreted the data, and wrote the manuscript. Dr. Semmlack, Mr. Kaplan, Dr. De Marchis, Dr. Rüegg, and Dr. Marsch interpreted the data, revised the manuscript, and substantially contributed to the inaugural draft. All authors approved the final submitted version. Mr. Kaplan has provided unsponsored grand rounds, published books on EEG, status epilepticus, and epilepsy for which he received honoraria, has consulted for Cadwell, has been on the board of the ABCN, ICCN, and the ACNS. Dr. Semmlack disclosed government work. Mr. Kaplan has provided unsponsored grand rounds; published books on electroencephalography (EEG), status epilepticus, and epilepsy for which he received honoraria; has consulted for Cadwell; and has been on the board of the ABCN, ICCN, and the ACNS. Dr. De Marchis is supported by the Swiss National Science Foundation; Science Funds of the University Hospital Basel and University of Basel; Bangerter-Rhyner Foundation; the Swisslife Jubiläumsstiftung for Medical Research; the Swiss Neurological Society; the Fondazione Dr. Ettore Balli; De Quervain research grant; and the Thermo Fisher GmbH. He received travel honoraria by Bayer and speaker honoraria by Medtronic and BMS/Pfizer. Dr. Rüegg received unconditional research grants from UCB-pharma. He received honoraria from serving on the scientific advisory boards of Desitin, Eisai, GlaxoSmithKline (GSK), and UCB-pharma; travel grants from GSK, Janssen-Cilag, and UCB-pharma; and speaker fees from UCB-pharma and from serving as a consultant for Eisai, GlaxoSmithKline, Janssen-Cilag, Pfizer, Novartis, and UCB-pharma. He does not hold any stocks of any pharmaceutical industries or manufacturers of medical devices. He received funding from Sandoz Switzerland; Novartis Oncology, Switzerland; Desitin GmbH, Switzerland; Editor Swiss EEG-Bulletin, support of UCB Switzerland and EGI USA Portland, currently Philips, Eindhoven, The Netherlands; and the Swiss Society of Clinical Neurophysiology and Swiss Neurological Society. He received funding from UCB-pharma, Novartis, and Swiss National Science Foundation Grants: grant number 320030_169379/1 and coapplicant for grants numbers 33CM30_125115/1 and 33CM30_140338/1; he disclosed that he is the president of the Swiss League against Epilepsy (no payments), Editor of EPILEPTOLOGIE (Journal of the Swiss League against Epilepsy) (no payments), and Editor of the Swiss EEG Bulletin (payments from UCB); he received honoraria from serving on the scientific advisory boards of Desitin, Eisai, GSK, and UCB-pharma; travel grants from GSK, Janssen-Cilag, and UCB-pharma; and speaker fees from UCB-pharma. Dr. Sutter received research grants from the Swiss National Foundation (No 320030_169379), the Research Fund of the University Basel, the Scientific Society Basel, and the Bangerter-Rhyner Foundation. He received personal grants from UCB-pharma and holds stocks from Novartis, Roche, and Johnson & Johnson. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at the University Hospital Basel, Basel, Switzerland. The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. For information regarding this article, E-mail: raoul.sutter@usb.ch Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Assessing Competence in Central Venous Catheter Placement by Pediatric Critical Care Fellows: A National Survey Study Objectives: To describe the current approach to initial training, ongoing skill maintenance, and assessment of competence in central venous catheter placement by pediatric critical care medicine fellows, a subset of trainees in whom this skill is required. Design: Cross-sectional internet-based survey with deliberate sampling. Setting: United States pediatric critical care medicine fellowship programs. Subjects: Pediatric critical care medicine program directors of Accreditation Council for Graduate Medical Education-accredited fellowship programs. Interventions: None. Measurements and Main Results: A working group of the Education in Pediatric Intensive Care Investigators research collaborative conducted a national study to assess the degree of standardization of training and competence assessment of central venous catheter placement across pediatric critical care medicine fellowship programs. After piloting, the survey was sent to all program directors (n = 67) of Accreditation Council for Graduate Medical Education-accredited pediatric critical care medicine programs between July 2017 and September 2017. The response rate was 85% (57/67). Although 98% of programs provide formalized central venous catheter placement training for first-year fellows, only 42% of programs provide ongoing maintenance training as part of fellowship. Over half (55%) of programs use a global assessment tool and 33% use a checklist-based tool when evaluating fellow central venous catheter placement competence under direct supervision. Only two programs (4%) currently use an assessment tool previously published and validated by the Education in Pediatric Intensive Care group. A majority (82%) of responding program directors believe that a standardized approach to assessment of central venous catheter competency across programs is important. Conclusions: Despite national mandates for skill competence by many accrediting bodies, no standardized system currently exists across programs for assessing central venous catheter placement. Most pediatric critical care medicine programs use a global assessment and decisions around the ability of a fellow to place a central venous catheter under indirect supervision are largely based upon subjective assessment of performance. Further investigation is needed to determine if this finding is consistent in other specialties/subspecialties, if utilization of standardized assessment methods can improve program directors' abilities to ensure trainee competence in central venous catheter insertion in the setting of variable training approaches, and if these findings are consistent with other procedures across critical care medicine training programs, adult and pediatric. 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 UL1 TR000445 NCATS/NIH (Research Electronic Data Capture [REDCap]). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: boyerd@email.chop.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Epidemiology of Hospital-Onset Versus Community-Onset Sepsis in U.S. Hospitals and Association With Mortality: A Retrospective Analysis Using Electronic Clinical Data Objectives: Prior studies have reported that hospital-onset sepsis is associated with higher mortality rates than community-onset sepsis. Most studies, however, have used inconsistent case-finding methods and applied limited risk-adjustment for potential confounders. We used consistent sepsis criteria and detailed electronic clinical data to elucidate the epidemiology and mortality associated with hospital-onset sepsis. Design: Retrospective cohort study. Setting: 136 U.S. hospitals in the Cerner HealthFacts dataset. Patients: Adults hospitalized in 2009–2015. Interventions: None. Measurements and Main Results: We identified sepsis using Centers for Disease Control and Prevention Adult Sepsis Event criteria and estimated the risk of in-hospital death for hospital-onset sepsis versus community-onset sepsis using logistic regression models. In patients admitted without community-onset sepsis, we estimated risk of death associated with hospital-onset sepsis using Cox regression models with sepsis as a time-varying covariate. Models were adjusted for baseline characteristics and severity of illness. Among 2.2 million hospitalizations, there were 95,154 sepsis cases: 83,620 (87.9%) community-onset sepsis and 11,534 (12.1%) hospital-onset sepsis (0.5% of hospitalized cohort). Compared to community-onset sepsis, hospital-onset sepsis patients were younger (median 66 vs 68 yr) but had more comorbidities (median Elixhauser score 14 vs 11), higher Sequential Organ Failure Assessment scores (median 4 vs 3), higher ICU admission rates (61% vs 44%), longer hospital length of stay (median 19 vs 8 d), and higher in-hospital mortality (33% vs 17%) (p < 0.001 for all comparisons). On multivariate analysis, hospital-onset sepsis was associated with higher mortality versus community-onset sepsis (odds ratio, 2.1; 95% CI, 2.0–2.2) and patients admitted without sepsis (hazard ratio, 3.0; 95% CI, 2.9–3.2). Conclusions: Hospital-onset sepsis complicated one in 200 hospitalizations and accounted for one in eight sepsis cases, with one in three patients dying in-hospital. Hospital-onset sepsis preferentially afflicted ill patients but even after risk-adjustment, they were twice as likely to die as community-onset sepsis patients; in patients admitted without sepsis, hospital-onset sepsis tripled the risk of death. Hospital-onset sepsis is an important target for surveillance, prevention, and quality improvement initiatives. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). This work was funded by the Centers for Disease Control and Prevention (U54CK000484), the Agency for Healthcare Research and Quality (K08HS025008 to Dr. Rhee), and intramural funds from the National Institutes of Health Clinical Center and National Institute of Allergy and Infectious Diseases (to Dr. Kadri). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, or the National Institutes of Health. Dr. Rhee received support for article research from the Agency for Healthcare Research and Quality and the Centers for Disease Control and Prevention (CDC). Drs. Rhee and Klompas received funding from UptoDate. Dr. Fram's institution received funding from Harvard Pilgrim Health Care Institute; he received funding from Commonwealth Informatics; and he disclosed work for hire. Dr. Kadri received support for article research from the National Institutes of Health, and he disclosed government work. Dr. Klompas' institution received funding from the CDC and Massachusetts Department of Public Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: crhee@bwh.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Frailty and Associated Outcomes and Resource Utilization Among Older ICU Patients With Suspected Infection Objectives: Suspected infection and sepsis are common conditions seen among older ICU patients. Frailty has prognostic importance among critically ill patients, but its impact on outcomes and resource utilization in older patients with suspected infection is unknown. We sought to evaluate the association between patient frailty (defined as a Clinical Frailty Scale ≥ 5) and outcomes of critically ill patients with suspected infection. We also evaluated the association between frailty and the quick Sequential Organ Failure Assessment score. Design: Analysis of a prospectively collected registry. Setting: Two hospitals within a single tertiary care level hospital system between 2011 and 2016. Patients: We analyzed 1,510 patients 65 years old or older (at the time of ICU admission) and with suspected infection at the time of ICU admission. Of these, 507 (33.6%) were categorized as "frail" (Clinical Frailty Scale ≥ 5). Interventions: None. Measurements and Main Results: The primary outcome was in-hospital mortality. A total of 558 patients (37.0%) died in-hospital. Frailty was associated with increased risk of in-hospital death (adjusted odds ratio, 1.81 [95% CIs, 1.34–2.49]). Frailty was also associated with higher likelihood of discharge to long-term care (adjusted odds ratio, 2.06 [95% CI, 1.50–2.64]) and higher likelihood of readmission within 30 days (adjusted odds ratio, 1.83 [95% CI, 1.38–2.34]). Frail patients had increased ICU resource utilization and total costs. The combination of frailty and quick Sequential Organ Failure Assessment greater than or equal to 2 further increased the risk of death (adjusted odds ratio, 7.54 [95% CI, 5.82–9.90]). Conclusions: The presence of frailty among older ICU patients with suspected infection is associated with increased mortality, discharge to long-term care, hospital readmission, resource utilization, and costs. This work highlights the importance of clinical frailty in risk stratification of older ICU patients with suspected infection. Drs. Fernando, McIsaac, Perry, Rochwerg, Bagshaw, and Kyeremanteng designed the study. Drs. Fernando, Dave, and Kyeremanteng gathered the data. Drs. Fernando, McIsaac, Perry, Rochwerg, Bagshaw, Thavorn, Seely, Forster, Fiest, Tran, Reardon, Tanuseputro, and Kyeremanteng analyzed the data. All authors wrote the manuscript. 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. Bagshaw is supported by a Canada Research Chair in Critical Care Nephrology. Dr. Seely holds patents related to multiple organ variability analysis and has shares in Therapeutic Monitoring Systems. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: sfernando@qmed.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Impact of Structured Pathways for Postcardiac Arrest Care: A Systematic Review and Meta-Analysis Objectives: Recent research has demonstrated value in selected therapeutic and prognostic interventions delivered to patients following cardiac arrest. The aim of this work was to determine if the implementation of a structured care pathway, which combines different interventions, could improve outcomes in survivors of cardiac arrest. Data Sources: PubMed and review of citations in retrieved articles. Study Selection: Randomized trials and prospective observational studies conducted in adult cardiac arrest patients, which evaluated the impact on outcome of a structured care pathway, defined as an organized set of interventions designed specifically for postcardiac arrest patients. Data Extraction: Data collected included study characteristics and methodologic quality, populations enrolled, interventions that were part of the cardiac arrest structured care pathway, and outcomes. The principal outcome was favorable functional status defined as a Cerebral Performance Category score of 1–2 at or after hospital discharge. Data Synthesis: The systematic search retrieved 481 articles of which nine (total, 1,994 patients) were selected for systematic review, and six (1,422 patients) met criteria for meta-analysis. Interventions in the care pathways included early coronary angiography with or without percutaneous coronary intervention (eight studies), targeted temperature management (nine studies), and protocolized management in the ICU (seven studies). Neurologic prognostication was not a part of any of the structured pathways. Meta-analysis found significantly higher odds of achieving a favorable functional outcome in patients who were treated in a structured care pathway, when compared with standard care (odds ratio, 2.35; 95% CI, 1.46–3.81). Conclusions: Following cardiac arrest, patients treated in a structured care pathway may have a substantially higher likelihood of favorable functional outcome than those who receive standard care. These findings suggest benefit of a highly organized approach to postcardiac arrest care, in which a cluster of evidence-based interventions are delivered by a specialized interdisciplinary team. Given the overall low certainty of evidence, definitive recommendations will need confirmation in additional high-quality studies. 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. Storm has a relationship with C. R. Bard GmbH (Wachhausstrasse, Karlsruhe, Germany) by having received honoraria and taking expert witness and with Zoll GmbH (Emil-Hoffmann-Straße, Köln, Germany) by having received honoraria. Dr. Leithner has received honoraria from Bard Medical and Edwards Lifesciences GmbH (Edisonstraße, Unterschleißheim, Germany) for work in a Critical Event Committee. Dr. Krannich has no conflict of interest related to this publication but independent from this publication and the presented topic, however, Dr. Krannich has a financial relationship to Pfizer GmbH (Linkstraße, Berlin, Germany). Dr. Suarez is the Chair of the Data and Safety Monitoring Board of the Impact of Fever Prevention in brain Injured Patients (INTREPID) Study (ClinicalTrials.gov Identifier: NCT02996266) funded by C. R. Bard (Murray Hill, NJ). Dr. Stevens has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: rstevens@jhmi.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182