Critical Care Medicine

Monocyte Distribution Width: A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency Department Patients Objectives: Most septic patients are initially encountered in the emergency department where sepsis recognition is often delayed, in part due to the lack of effective biomarkers. This study evaluated the diagnostic accuracy of peripheral blood monocyte distribution width alone and in combination with WBC count for early sepsis detection in the emergency department. Design: An Institutional Review Board approved, blinded, observational, prospective cohort study conducted between April 2017 and January 2018. Setting: Subjects were enrolled from emergency departments at three U.S. academic centers. Patients: Adult patients, 18–89 years, with complete blood count performed upon presentation to the emergency department, and who remained hospitalized for at least 12 hours. A total of 2,212 patients were screened, of whom 2,158 subjects were enrolled and categorized per Sepsis-2 criteria, such as controls (n = 1,088), systemic inflammatory response syndrome (n = 441), infection (n = 244), and sepsis (n = 385), and Sepsis-3 criteria, such as control (n = 1,529), infection (n = 386), and sepsis (n = 243). Interventions: The primary outcome determined whether an monocyte distribution width of greater than 20.0 U, alone or in combination with WBC, improves early sepsis detection by Sepsis-2 criteria. Secondary endpoints determined monocyte distribution width performance for Sepsis-3 detection. Measurements and Main Results: Monocyte distribution width greater than 20.0 U distinguished sepsis from all other conditions based on either Sepsis-2 criteria (area under the curve, 0.79; 95% CI, 0.76–0.82) or Sepsis-3 criteria (area under the curve, 0.73; 95% CI, 0.69–0.76). The negative predictive values for monocyte distribution width less than or equal to 20 U for Sepsis-2 and Sepsis-3 were 93% and 94%, respectively. Monocyte distribution width greater than 20.0 U combined with an abnormal WBC further improved Sepsis-2 detection (area under the curve, 0.85; 95% CI, 0.83–0.88) and as reflected by likelihood ratio and added value analyses. Normal WBC and monocyte distribution width inferred a six-fold lower sepsis probability. Conclusions: An monocyte distribution width value of greater than 20.0 U is effective for sepsis detection, based on either Sepsis-2 criteria or Sepsis-3 criteria, during the initial emergency department encounter. In tandem with WBC, monocyte distribution width is further predicted to enhance medical decision making during early sepsis management in the emergency department. 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. 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 a grant from Beckman Coulter. Drs. Crouser’s, Parrillo’s, Bicking’s, Peck-Palmer’s, Julian’s, Kleven’s, Raj’s, and Procopio’s institutions received funding from Beckman Coulter. Dr. Crouser’s institution received funding from Foundation for Sarcoidosis Research and the National Institutes of Health (NIH), received funding from ATyr Pharmaceutical (consulting), and disclosed that he designed the trial in coordination with Beckman Coulter. Dr. Parrillo received funding from National Heart, Lung, and Blood Institute-NIH Heart Failure Network, consulting fees for some of the work performed, and Asahi-Kasei America (consulting). Dr. Seymour’s institution received funding from the NIH and received support for article research from the NIH. Drs. Seymour, Angus, and Esguerra received funding from Beckman Coulter. Drs. Bicking, Esguerra, Kleven, Raj, Procopio, and Tejidor disclosed off-label product use of Beckman Coulter equipment used to measure monocyte distribution width, the entity under study and described in the article. Dr. Esguerra received speaker honoraria for presenting data related to the pilot study to audiences internationally in Brussels and in Hong Kong. Dr. Peck-Palmer’s institution received funding from Roche Diagnostics. Dr. Magari disclosed that he and his spouse are Beckman Coulter employees. Drs. Magari and Tejidor disclosed work for hire. Drs. Careaga and Tejidor disclosed that they are Beckman Coulter employees. For information regarding this article, E-mail: elliott.crouser@osumc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study Objectives: Midodrine is an α1-agonist approved for orthostatic hypotension. Recently, it has received attention as an oral vasopressor to facilitate ICU discharge. The purpose of this study was to identify the incidence of continuation of newly initiated midodrine upon ICU and hospital discharge and identify risk factors associated with its occurrence. Design: Single-center retrospective study. Setting: ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. Patients: Adult patients admitted to any ICU who received new midodrine for hypotension and survived to discharge. Interventions: None. Measurements and Main Results: During the study period, 1,010 patients were newly started on midodrine and survived to ICU discharge. Midodrine was continued in 67% (672/1,010) of patients at ICU discharge. Admission to cardiovascular surgery ICU and mixed medical/surgical ICU was a risk factor for midodrine continuation at ICU discharge (odds ratio, 3.94 [2.50–6.21] and 2.03 [1.29–3.20], respectively). At hospital discharge, 34% (311/909) of patients were continued on midodrine therapy. History of congestive heart failure predicted midodrine continuation at hospital discharge (odds ratio, 1.49 [1.05–2.12]). Hypertension and use of mechanical ventilation were associated with a decreased odds of midodrine prescription at both ICU and hospital discharge. Of those discharged from the ICU or hospital on midodrine, 50% were concomitantly prescribed antihypertensives. Discharge from the ICU on midodrine was associated with a significantly shorter ICU length of stay (7.5 ± 8.9 vs 10.6 ± 13.4 d) and reduced risk of in-hospital mortality (hazard ratio, 0.47 [95% CI, 0.32–0.70]; p < 0.001), despite no difference in baseline severity of illness scores. In contrast, patients discharged from the hospital on midodrine had a higher risk of 1-year mortality (hazard ratio, 1.60 [95% CI, 1.26–2.04]; p < 0.001). Conclusions: This study established a high prevalence of midodrine continuation in transitions of care. The risks and benefits of this practice remain unclear. Future studies should explore the impact of this practice on patient outcomes and resource utilization. These insights could be used to model interventions for proper tapering, discontinuation, or follow-up of new start midodrine. This work was performed at the Mayo Clinic, Rochester, MN. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Nei and Barreto disclosed off-label product use of midodrine. Dr. Barreto received funding from Fast Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: barreto.erin@mayo.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Association Between Critical Care Admissions and Cognitive Trajectories in Older Adults Objectives: Patients requiring admission to an ICU may subsequently experience cognitive decline. Our objective was to investigate longitudinal cognitive trajectories in older adults hospitalized in ICUs. We hypothesized that individuals hospitalized for critical illness develop greater cognitive decline compared with those who do not require ICU admission. Design: A retrospective cohort study using prospectively collected cognitive scores of participants enrolled in the Mayo Clinic Study of Aging and ICU admissions retrospectively ascertained from electronic medical records. A covariate-adjusted linear mixed effects model with random intercepts and slopes assessed the relationship between ICU admissions and the slope of global cognitive z scores and domains scores (memory, attention/executive, visuospatial, and language). Setting: ICU admissions and cognitive scores in the Mayo Clinic Study of Aging from October 1, 2004, to September 11, 2017. Patients: Nondemented participants age 50 through 91 at enrollment in the Mayo Clinic Study of Aging with an initial cognitive assessment and at least one follow-up visit. Interventions: None. Measurements and Main Results: Of 3,673 participants, 372 had at least one ICU admission with median (25–75th percentile) follow-up after first ICU admission of 2.5 years (1.2–4.4 yr). For global cognitive z score, admission to an ICU was associated with greater decline in scores over time compared with participants not requiring ICU admission (difference in annual slope = –0.028; 95% CI, –0.044 to –0.012; p < 0.001). ICU admission was associated with greater declines in memory (–0.029; 95% CI, –0.047 to –0.011; p = 0.002), attention/executive (–0.020; 95% CI, –0.037 to –0.004; p = 0.016), and visuospatial (–0.013; 95% CI, –0.026 to –0.001; p = 0.041) domains. ICU admissions with delirium were associated with greater declines in memory (interaction p = 0.006) and language (interaction p = 0.002) domains than ICU admissions without delirium. Conclusions: In older adults, ICU admission was associated with greater long-term cognitive decline compared with patients without ICU admission. These findings were more pronounced in those who develop delirium while in the ICU. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs. Schulte, Warner, Rabinstein, and Sprung contributed to conception and design of the work, interpretation of data, analysis and interpretation of data, drafting of the work and revisions for important intellectual content, final approval. Drs. Martin, Mielke, Knopman, Petersen, Weingarten, and Warner contributed to critical revisions of the work for important intellectual content and final approval: Dr. Deljou contributed to acquisition and interpretation of data. Drs. Hanson and Schroeder contributed to data analysis, statistical work, critical revisions of the work for important intellectual content, and final approval. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the National Institutes of Health grants U01 AG006786 (principal investigator [PI]: to R.C.P), P50 AG016574 (PI: to R.C.P), RF1 AG55151 (PI: to M.M.M), by the Robert H. and Clarice Smith and Abigail van Buren Alzheimer’s Disease Research Program, the Rochester Epidemiology Project (R01 AG034676) and the Mayo Clinic Center for Translational Sciences Activities (CTSA), grant number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). In addition, this study was supported, in part, by CTSA Grant Number KL2 TR002379 to M.A.W from NCATS. Drs. Schulte, Mielke, Knopman, and Petersen received support for article research from the National Institutes of Health. Dr. Martin disclosed that he serves on the Board of Directors for the American Society of Anesthesiologists (ASA), he receives an annual stipend from ASA for contributions to the Patient Safety Continuing Medical Education Editorial Board, and he and Mayo Clinic owns equity and receives royalties for work licensed through Mayo Clinic to Nevro, Inc, a publicly held company, for contributions related to the use of nerve signal modulation to treat central, autonomic, and peripheral nervous system disorders, including pain. Dr. Mielke’s institution received funding from Biogen and Lunbeck, and she received funding from Eli Lilly. Dr. Knopman received funding from Washington University (Data Safety Monitoring Board activities). Dr. Petersen’s institution received funding from National Institute on Aging; he received funding from Roche (consultant), Merck (consultant), Genentech (DSMB), Biogen, Eisai, and GE Healthcare; and he received other support from benefactors through the Mayo Clinic. Dr. Weingarten received funding from Medtronic (served as chairman of the clinical event committee of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial, which examined postoperative capnography monitoring) and Merck (received an investigator-initiated, unrestricted grant to study the effects of sugammadex on return of postoperative bowel function), and he disclosed work for hire. Dr. Warner’s institution received funding from Center for Translational Sciences Activities Grant Number KL2 TR002379 from the National Center for Advancing Translational Science. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: schulte.phillip@mayo.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Early Enteral Nutrition in Patients Undergoing Sustained Neuromuscular Blockade: A Propensity-Matched Analysis Using a Nationwide Inpatient Database Objectives: Whether enteral nutrition should be postponed in patients undergoing sustained treatment with neuromuscular blocking agents remains unclear. We evaluated the association between enteral nutrition initiated within 2 days of sustained neuromuscular blocking agent treatment and in-hospital mortality. Design: Retrospective administrative database study from July 2010 to March 2016. Setting: More than 1,200 acute care hospitals covering approximately 90% of all tertiary-care emergency hospitals in Japan. Patients: Mechanically ventilated patients, who had undergone sustained treatment with neuromuscular blocking agents in an ICU, were retrospectively reviewed. We defined patients who received sustained treatment with neuromuscular blocking agents as those who received either rocuronium at greater than or equal to 250 mg/d or vecuronium at greater than or equal to 50 mg/d for at least 2 consecutive days. Interventions: Enteral nutrition started within 2 days from the initiation of neuromuscular blocking agents (defined as early enteral nutrition). Measurements and Main Results: We identified 2,340 eligible patients during the 69-month study period. Of these, 378 patients (16%) had received early enteral nutrition. One-to-three propensity score matching created 374–1,122 pairs. The in-hospital mortality rate was significantly lower in the early than late enteral nutrition group (risk difference, –6.3%; 95% CI, –11.7% to –0.9%). There was no significant difference in the rate of hospital pneumonia between the two groups (risk difference, 2.8%; 95% CI, –2.7% to 8.3%). Length of hospital stay among survivors was significantly shorter in the early compared with the late enteral nutrition group (risk difference, –11.4 d; 95% CI, –19.1 to –3.7 d). There was no significant difference between the two groups in length of ICU stay or length of mechanical ventilation among survivors. Conclusions: According to this retrospective database study, early enteral nutrition may be associated with lower in-hospital mortality with no increase in-hospital pneumonia in patients undergoing sustained treatment with neuromuscular blocking agents. 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 the Ministry of Health, Labour and Welfare of Japan (H30-Policy-Designated-004 and H29-ICT-Genral-004) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (17H04141). Dr. Ohbe received support for article research from the Ministry of Health, Labour and Welfare of Japan and the Ministry of Education, Culture, Sports, Science and Technology of Japan. Dr. Yasunaga’s institution received funding from the Ministry of Health, Labour and Welfare, Japan and the Ministry of Education, Culture, Sports, Science and Technology, Japan. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at The University of Tokyo. For information regarding this article, E-mail: hohbey@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Trends and Outcomes in Sepsis Hospitalizations With and Without Atrial Fibrillation: A Nationwide Inpatient Analysis Objectives: Atrial fibrillation is frequently seen in sepsis-related hospitalizations. However, large-scale contemporary data from the United States comparing outcomes among sepsis-related hospitalizations with versus without atrial fibrillation are limited. The aim of our study was to assess the frequency of atrial fibrillation and its impact on outcomes of sepsis-related hospitalizations. Design: Retrospective cohort study. Setting: The National Inpatient Sample databases (2010–2014). Patients: Primary discharge diagnosis of sepsis with and without atrial fibrillation were identified using prior validated International Classification of Diseases, 9th Edition, Clinical Modification codes. Interventions: None. Measurements and Main Results: Overall, 5,808,166 hospitalizations with the primary diagnosis of sepsis, of which 19.4% (1,126,433) were associated with atrial fibrillation. The sepsis-atrial fibrillation cohort consisted of older (median [interquartile range] age of 79 yr [70–86 yr] vs 67 yr [53–79 yr]; p < 0.001) white (80.9% vs 68.8%; p < 0.001) male (51.1% vs 47.5%; p < 0.001) patients with an extended length of stay (median [interquartile range] 6 d [4–11 d] vs 5 d [3–9 d]; p < 0.001) and higher hospitalization charges (median [interquartile range] $44,765 [$23,234–$88,657] vs $35,737 [$18,767–$72,220]; p < 0.001) as compared with the nonatrial fibrillation cohort. The all-cause mortality rate in the sepsis-atrial fibrillation cohort was significantly higher (18.4% and 11.9%; p = 0.001) as compared with those without atrial fibrillation. Although all-cause mortality (20.4% vs 16.6%) and length of stay (median [interquartile range] 7 d [4–11 d] vs 6 d [4–10 d]) decreased between 2010 and 2014, hospitalization charges increased (median [interquartile range] $41,783 [$21,430–$84,465] vs $46,251 [$24,157–$89,995]) in the sepsis-atrial fibrillation cohort. The greatest predictors of mortality in the atrial fibrillation-sepsis cohort were African American race, female gender, advanced age, and the presence of medical comorbidities. Conclusions: The presence of atrial fibrillation among sepsis-related hospitalizations is a marker of poor prognosis and increased mortality. Although we observed rising trends in sepsis and sepsis-atrial fibrillation–related hospitalizations during the study period, the rate and odds of mortality progressively decreased. 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: rsachdeva@msm.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome Objectives: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. Design: Controlled, randomized, double-blinded laboratory study. Setting: Animal research laboratories. Subjects: Adult Wistar male rats (n = 110). Interventions: Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed. Measurements and Main Results: After argon inhalation for 24 hours immediately following “severe permanent ischemia” induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed. Conclusions: Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion. 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 a DREAM Award from the Department of Anesthesiology at Duke University Medical Center. Dr. Sheng’s institution received funding from the National Institutes of Health (NIH). Drs. Sheng and Turner received support for article research from the NIH. Dr. Yang received support for article research from departmental funds. Dr. Hoffmann received support for article research from the Department of Duke Anesthesiology DREAM award, and he disclosed off-label product use of noble gas argon. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: ulrike.hoffmann@duke.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

At-Risk Drinking Is Independently Associated With Acute Kidney Injury in Critically Ill Patients Objectives: Unhealthy use of alcohol and acute kidney injury are major public health problems, but little is known about the impact of excessive alcohol consumption on kidney function in critically ill patients. We aimed to determine whether at-risk drinking is independently associated with acute kidney injury in the ICU and at ICU discharge. Design: Prospective observational cohort study. Setting: A 21-bed polyvalent ICU in a university hospital. Patients: A total of 1,107 adult patients admitted over a 30-month period who had an ICU stay of greater than or equal to 3 days and in whom alcohol consumption could be assessed. Interventions: None. Measurements and Main Results: We assessed Kidney Disease Improving Global Outcomes stages 2–3 acute kidney injury in 320 at-risk drinkers (29%) and 787 non–at-risk drinkers (71%) at admission to the ICU, within 4 days after admission and at ICU discharge. The proportion of patients with stages 2–3 acute kidney injury at admission to the ICU (42.5% vs 18%; p < 0.0001) was significantly higher in at-risk drinkers than in non–at-risk drinkers. Within 4 days and after adjustment on susceptible and predisposing factors for acute kidney injury was performed, at-risk drinking was significantly associated with acute kidney injury for the entire population (odds ratio, 2.15; 1.60–2.89; p < 0.0001) in the subgroup of 832 patients without stages 2–3 acute kidney injury at admission to the ICU (odds ratio, 1.44; 1.02–2.02; p = 0.04) and in the subgroup of 971 patients without known chronic kidney disease (odds ratio, 1.92; 1.41–2.61; p < 0.0001). Among survivors, 22% of at-risk drinkers and 9% of non–at-risk drinkers were discharged with stages 2–3 acute kidney injury (p < 0.001). Conclusions: Our results suggest that chronic and current alcohol misuse in critically ill patients is associated with kidney dysfunction. The systematic and accurate identification of patients with alcohol misuse may allow for the prevention of acute kidney injury. Dr. Gacouin had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Gacouin and Tadié drafted the work. All authors contributed to the conception and design of the work, data acquisition, and analysis. All authors contributed to the interpretation of data for the work. All authors revised it critically for important intellectual content. All authors gave final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. 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: arnaud.gacouin@chu-rennes.fr Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Cardiac Arrest Prior to Venoarterial Extracorporeal Membrane Oxygenation: Risk Factors for Mortality Objectives: Mortality after cardiac arrest remains high despite initiation of venoarterial extracorporeal membrane oxygenation. We aimed to identify pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality in patients with witnessed cardiac arrest and with greater than or equal to 1 minute of cardiopulmonary resuscitation before venoarterial extracorporeal membrane oxygenation. The association between preimplant variables and all-cause mortality at 90 days was analyzed with multivariable logistic regression. Design: Retrospective observational cohort study. Setting: Tertiary medical center. Patients: Seventy-two consecutive patients with cardiac arrest prior to venoarterial extracorporeal membrane oxygenation cannulation. Interventions: None. Measurements and Main Results: Median age was 56 years (interquartile range, 43–56 yr), 75% (n = 54) were men. Out-of-hospital cardiac arrest occurred in 12% (n = 9) of the patients. Initial cardiac rhythm was nonshockable in 57% (n = 41) and shockable in 43% (n = 31) of patients. Median cardiopulmonary resuscitation duration was 21 minutes (interquartile range, 10–73 min; range, 1–197 min]. No return of spontaneous circulation was present in 64% (n = 46) and postarrest cardiogenic shock in 36% (n = 26) of the patients at venoarterial extracorporeal membrane oxygenation cannulation. Median duration of venoarterial extracorporeal membrane oxygenation was 5 days (interquartile range, 2–12 d). The 90-day overall mortality and in-hospital mortality were 57% (n = 41), 53% (n = 38) died during venoarterial extracorporeal membrane oxygenation, and 43% (n = 31) were successfully weaned. All survivors had Cerebral Performance Category score 1–2 at discharge to home. Multivariable logistic regression analysis identified initial nonshockable cardiac arrest rhythm (odds ratio, 12.2; 95% CI, 2.83–52.7; p = 0.001), arterial lactate (odds ratio per unit, 1.15; 95% CI, 1.01–1.31; p = 0.041), and ischemic heart disease (7.39; 95% CI, 1.57–34.7; p = 0.011) as independent risk factors of 90-day mortality, whereas low-flow duration, return of spontaneous circulation, and age were not. Conclusions: In 72 patients with cardiac arrest before venoarterial extracorporeal membrane oxygenation initiation, nonshockable rhythm, arterial lactate, and ischemic heart disease were identified as independent pre-venoarterial extracorporeal membrane oxygenation risk factors of 90-day mortality. The novelty of this study is that the metabolic state, expressed as level of lactate just before venoarterial extracorporeal membrane oxygenation initiation seems more predictive of outcome than cardiopulmonary resuscitation duration or absence of return of spontaneous circulation. 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. This work was performed at the Karolinska University Hospital, SE-17176 Stockholm, Sweden. For information regarding this article, E-mail: thomas.fux@sll.se Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Effect of Increasing Blood Pressure With Noradrenaline on the Microcirculation of Patients With Septic Shock and Previous Arterial Hypertension Objectives: To assess whether an increase in mean arterial pressure in patients with septic shock and previous systemic arterial hypertension changes microcirculatory and systemic hemodynamic variables compared with patients without arterial hypertension (control). Design: Prospective, nonblinded, interventional study. Setting: Three ICUs in two teaching hospitals. Patients: After informed consent, we included patients older than 18 years with septic shock for at least 6 hours, sedated, and under mechanical ventilation. We paired patients with and without arterial hypertension by age. Interventions: After obtaining systemic and microcirculation baseline hemodynamic variables (time 0), we increased noradrenaline dose to elevate mean arterial pressure up to 85–90 mm Hg before collecting a new set of measurements (time 1). Measurements and Main Results: We included 40 patients (20 in each group). There was no significant difference in age between the groups. After the rise in mean arterial pressure, there was a significant increase in cardiac index and a slight but significant reduction in lactate in both groups. We observed a significant improvement in the proportion of perfused vessels (control: 57.2 ± 14% to 66 ± 14.8%; arterial hypertension: 61.4 ± 12.3% to 70.8 ± 7.1%; groups: p = 0.29; T0 and T1: p < 0.001; group and time interaction: p = 0.85); perfused vessels density (control: 15.6 ± 4 mm/mm2 to 18.6 ± 4.5 mm/mm2; arterial hypertension: 16.4 ± 3.5 mm/mm2 to 19.1 ± 3 mm/mm2; groups: p = 0.51; T0 and T1: p < 0.001; group and time interaction: p = 0.70), and microcirculatory flow index (control: 2.1 ± 0.6 to 2.4 ± 0.6; arterial hypertension: 2.1 ± 0.5 to 2.6 ± 0.2; groups: p = 0.71; T0 and T1: p = 0.002; group and time interaction: p = 0.45) in both groups. Conclusions: Increasing mean arterial pressure with noradrenaline in septic shock patients improves density and flow in small vessels of sublingual microcirculation. However, this improvement occurs both in patients with previous arterial hypertension and in those without arterial hypertension. 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 Fundação de Pesquisa do Estado de São Paulo—Grant 2012/19051-1. Drs. Fiorese Coimbra’s, de Freitas’s, Bafi’s, Pinheiro’s, Nunes’s, and Machado’s institution received funding from Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP, a government grant agency from State of São Paulo. Dr. de Azevedo disclosed that he does not have any potential conflicts of interest. Trial registration: ClinicalTrials.gov NCT02519699. For information regarding this article, E-mail: karla.tuanny@hotmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Untangling Infusion Confusion: A Comparative Evaluation of Interventions in a Simulated Intensive Care Setting Objectives: Assess interventions’ impact on preventing IV infusion identification and disconnection mix-ups. Design: Experimental study with repeated measures design. Setting: High fidelity simulated adult ICU. Subjects: Forty critical care nurses. Interventions: Participants had to correctly identify infusions and disconnect an infusion in four different conditions: baseline (current practice); line labels/organizers; smart pump; and light-linking system. Measurements and Main Results: Participants identified infusions with significantly fewer errors when using line labels/organizers (0; 0%) than in the baseline (12; 7.7%) and smart pump conditions (10; 6.4%) (p < 0.01). The light-linking system did not significantly affect identification errors (5; 3.2%) compared with the other conditions. Participants were significantly faster identifying infusions when using line labels/organizers (0:31) than in the baseline (1:20), smart pump (1:29), and light-linking (1:22) conditions (p < 0.001). When disconnecting an infusion, there was no significant difference in errors between conditions, but participants were significantly slower when using the smart pump than all other conditions (p < 0.001). Conclusions: The results suggest that line labels/organizers may increase infusion identification accuracy and efficiency. 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. This work was performed at a Toronto hospital. This study was funded by Health Quality Ontario and the Association for the Advancement of Medical Instrumentation Foundation. Mr. Fan and Dr. Trbovich have received presentation honoraria from Becton Dickinson (BD), and Dr. Trbovich is the principal applicant on a grant (ROR2017-04260JH - North York General Hospital [NYGH]) from BD paid to NYGH (unrelated to this study). Ms. Koczmara’s and Dr. Trbovich’s institutions received funding from Health Quality Ontario (agency of the Ontario Ministry of Health and Long-term Care). Dr. Trbovich’s institution received funding from Association for the Advancement of Medical Instrumentation Foundation. Dr. Trbovich's institution received funding from Becton Dickinson Canada (paid the travel costs for team members to present the research findings to their Alaris infusion product team). Ms. Pinkney, Mr. Fan, Ms. Koczmara, and Dr. Trbovich disclosed work for hire, and they disclosed off-label product use of Nurse Buddy II (Verafied Medical Innovations LLC, American Canyon, CA), and prototype Light Linking System (developed by research team solely for this research study; not for sale and no commercialization plans). Mr. Fan and Dr. Trbovich disclosed working on a project aimed at adapting pre-existing e-learning modules regarding elastomeric infusors for Baxter Canada. Ms. Koczmara received funding from a consulting honorarium paid to Institute for Safe Medication Practices Canada to attend and participate in Hospira Infusion Systems 1-day Conference “Canadian Infusion Pump Safety Collaborative Forum.” Address requests for reprints to: Sonia J. Pinkney, MHSc, PEng, Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, Toronto, ON, M5T 3M6, Canada. E-mail: Sonia.pinkney@uhn.ca Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.