critical care

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.

The Effectiveness of α2Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study Objectives: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. Design: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11–16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. Setting: Two tertiary PICUs. Patients: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. Interventions: None. Measurements and Main Results: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72–75%) of the study time compared with the unexposed group at 70% (95% CI, 67–72%) giving a ratio of 1.06 (95% CI, 1.02–1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3–11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 μg/kg/hr (95% CI, –0.68 to 1.18 μg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. Conclusions: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use. 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 project received funding from the Children's Fund for Health at Children's University Hospital, Temple Street, Dublin, Ireland. The authors disclosed that they have no potential conflicts of interest. This work was carried out at the Royal College of Surgeons in Ireland. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For information regarding this article, E-mail: johnhayden@rcsi.ie Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial Objectives: To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa. Design: Randomized, controlled, unblinded study. Setting: Two ICUs of two university hospitals. Patients: Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation. Interventions: Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s). Measurements and Main Results: Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601–16,031 U] vs 20,710 U [95% CI, 15,343–27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5–53.2 s] vs 55.5 s [95% CI, 50.4–61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07–0.18] vs 0.27 [95% CI, 0.17–0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes. Conclusions: Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation. The complete list of board members for the International ECMO Network (ECMONet) is: Laurent Brochard, Daniel Brodie, Alain Combes, Eddy Fan, Niall Ferguson, John Fraser, Carol Hodgson, Alain Mercat, Thomas Mueller, Vin Pellegrino, Antonio Pesenti, Marco Ranieri, Art Slutsky, Danny McAuley, and Michael Quintel. Drs. Aubron and McQuilten have contributed equally to this work and are 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). This study was funded by an Australian and New Zealand College of Anaesthestists Project Grant (2015/007). This work was also supported by the Australian National Health and Medical Research Council (NHMRC) Centre of Research Excellence for Patient Blood Management in Critical Illness and Trauma (APP1040971). Dr. McQuilten is supported by a NHMRC Early Career Fellowship (APP1111485). Dr. McQuilten disclosed that she is employed by Monash University Transfusion Research Unit that has received financial support from Alexion, Amgen, Bayer, Celgene, CSL Behring, Janssen-Cilag, Takeda, Novartis, Australian Red Cross Blood Service, New Zealand Blood Service, Department of Health Victoria (Australia), and Myeloma Foundation of Australia. None of these funding sources had any involvement the design or conduct of this study. Drs. Board's and McIlroy's institutions received funding from Australia and New Zealand College of Anaesthetists. Dr. Board disclosed off-label product use of heparin low-dose protocol. Dr. Buhr's institution received funding from Alfred Health and the Intensive Care Foundation (research grant). Dr. Hodgson disclosed that she is employed by Monash University and she holds a Heart Foundation of Australia Future Leader Fellowship. Dr. Pellegrino received accommodation support for European ECMONet meetings where the work was presented during development. Dr. Tran received funding from Novartis, Shire, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: cecile.aubron@chu-brest.fr; cecile.aubron@monash.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Fresh Red Cells for Transfusion in Critically Ill Adults: An Economic Evaluation of the Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Clinical Trial Objectives: Trials comparing the effects of transfusing RBC units of different storage durations have considered mortality or morbidity as outcomes. We perform the first economic evaluation alongside a full age of blood clinical trial with a large population assessing the impact of RBC storage duration on quality-of-life and costs in critically ill adults. Design: Quality-of-life was measured at 6 months post randomization using the EuroQol 5-dimension 3-level instrument. The economic evaluation considers quality-adjusted life year and cost implications from randomization to 6 months. A generalized linear model was used to estimate incremental costs (2016 U.S. dollars) and quality-adjusted life years, respectively while adjusting for baseline characteristics. Setting: Fifty-nine ICUs in five countries. Patients: Adults with an anticipated ICU stay of at least 24 hours when the decision had been made to transfuse at least one RBC unit. Interventions: Patients were randomized to receive either the freshest or oldest available compatible RBC units (standard practice) in the hospital transfusion service. Measurements and Main Results: EuroQol 5-dimension 3-level utility scores were similar at 6 months—0.65 in the short-term and 0.63 in the long-term storage group (difference, 0.02; 95% CI, –0.00 to 0.04; p = 0.10). There were no significant differences in resource use between the two groups apart from 3.0 fewer hospital readmission days (95% CI, –5.3 to –0.8; p = 0.01) during follow-up in the short-term storage group. There were no significant differences in adjusted total costs or quality-adjusted life years between the short- and long-term storage groups (incremental costs, –$2,358; 95% CI, –$5,586 to $711) and incremental quality-adjusted life years: 0.003 quality-adjusted life years (95% CI, –0.003 to 0.008). Conclusions: Without considering the additional supply cost of implementing a freshest available RBC strategy for critical care patients, there is no evidence to suggest that the policy improves quality-of-life or reduces other costs compared with standard transfusion practice. This work was performed at the Centre for Health Economics, Monash Business School, Monash University, Caulfield, VIC, Australia. 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 full list of board members of the Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Investigators is provided in the Supplementary Appendix (Supplemental Digital Content 1,http://links.lww.com/CCM/E540). The TRANSFUSE trial was supported, in part, by grants from the Australian National Health and Medical Research Council (APP102064 and APP1040971), the Health Research Council of New Zealand (12/575), and the Irish Health Research Board (HRA-DI-2015–589 and CTN-2014-012) and by funding from the Australian Red Cross Blood Service. Ms. Higgins's and Ms. Murray's institutions received funding from Australian National Health and Medical Research Council (NHMRC) and Australian Red Cross Blood Service. Drs. Cooper's and Gantner's institutions received funding from NHMRC, Health Research Council of New Zealand, and Irish Health Research Board, and they received other support from Australian Red Cross Blood Service. Dr. Cooper received funding from Eustralis Pharmaceuticals (consulting) and National Blood Authority, Australia. Dr. French's institution received funding from NHMRC. Dr. Irving's institution received funding from the Australian Government (via the National Blood Authority). Dr. McQuilten's institution received funding from Abbvie, Celgene, Janssen-Cilag, CSL Biotherapies, and Gilead Sciences (for research undertaken by the Transfusion Research Unit). The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Zoe K. McQuilten, PhD, Department of Epidemiology and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, VIC 3004, Australia. E-mail: zoe.mcquilten@monash.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182,alsfakia@gmail.com