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A Hogewoning,1,* AJAE Van de Loo,1,* M Mackus,1 SJ Raasveld,1 R De Zeeuw,1 ER Bosma,1 NH Bouwmeester,1 KA Brookhuis,2 J Garssen,1,3 JC Verster1,4 1Division of Pharmacology, Utrecht University, Utrecht, 2Faculty of Behavioral and Social Sciences, Groningen University, Groningen, 3Nutricia Research, Utrecht, the Netherlands; 4Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia *These authors contributed equally to this work Background: A number of social drinkers claim that they do not experience next-day hangovers despite consuming large quantities of alcohol. The aim of this study was to investigate the characteristics of drinkers who claim to be hangover immune and compare them with drinkers who do report having hangovers. Methods: A total of 36 social drinkers participated in a naturalistic study consisting of a hangover day (alcohol consumed) and a control day (no alcohol consumed). Data were collected on alcohol consumption, demographics, sleep, next-day adverse effects, and mood. Data from drinkers with a hangover (N=18) were compared with data from drinkers who claim to be hangover immune (N=18). Results: Drinkers with a hangover reported drowsiness-related symptoms, symptoms related to reduced cognitive functioning, and classic hangover symptoms such as headache, nausea, dizziness, weakness, and stomach pain. Corresponding mood changes comprised increased feelings of depression, anger–hostility, fatigue, and reduced vigor–activity. In contrast, hangover-immune drinkers reported relatively few hangover symptoms, with only mild corresponding severity scores. The reported symptoms were limited to drowsiness-related symptoms such as sleepiness and being tired. The classic hangover symptoms were usually not reported by these drinkers. Conclusion: In contrast to drinkers with a hangover, for those who claim to be hangover immune, next-day adverse effects of alcohol consumption are limited to a mild increase in drowsiness-related symptoms. Keywords: alcohol, hangover, symptoms, mood, immunity

Background: Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study., Study Design and Methods: A patient-level comparison of CVC-related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test., Results: Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044-0.51) for the cutoff point grade 1 (i.e., self-limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review., Discussion: Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment., (© 2024 The Author(s). Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice., Objective: To evaluate and describe ICU RBC transfusion practices worldwide., Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks., Exposure: ICU stay., Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused., Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL., Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Background: Evidence-based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single-center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients., Methods: This international mixed-method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post-cardiotomy) and non-surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion., Results: Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st-3rd quartile 3-8), patients received a median total of eight RBC units (1st-3rd quartile 3-17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO-run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders., Conclusion: RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Thrombocytopenia, hemorrhage and platelet transfusion are common in patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO). However, current literature is limited to small single-center experiences with high degrees of heterogeneity. Therefore, we aimed to ascertain in a multicenter study the course and occurrence rate of thrombocytopenia, and to assess the association between thrombocytopenia, hemorrhage and platelet transfusion during VA ECMO., Methods: This was a sub-study of a multicenter (N = 16) study on transfusion practices in patients on VA ECMO, in which a retrospective cohort (Jan-2018-Jul-2019) focusing on platelets was selected. The primary outcome was thrombocytopenia during VA ECMO, defined as mild (100-150·10 9 /L), moderate (50-100·10 9 /L) and severe (< 50·10 9 /L). Secondary outcomes included the occurrence rate of platelet transfusion, and the association between thrombocytopenia, hemorrhage and platelet transfusion, assessed through mixed-effect models., Results: Of the 419 patients included, median platelet count at admission was 179·10 9 /L. During VA ECMO, almost all (N = 398, 95%) patients developed a thrombocytopenia, of which a significant part severe (N = 179, 45%). One or more platelet transfusions were administered in 226 patients (54%), whereas 207 patients (49%) suffered a hemorrhagic event during VA ECMO. In non-bleeding patients, still one in three patients received a platelet transfusion. The strongest association to receive a platelet transfusion was found in the presence of severe thrombocytopenia (adjusted OR 31.8, 95% CI 17.9-56.5). After including an interaction term of hemorrhage and thrombocytopenia, this even increased up to an OR of 110 (95% CI 34-360)., Conclusions: Thrombocytopenia has a higher occurrence than is currently recognized. Severe thrombocytopenia is strongly associated with platelet transfusion. Future studies should focus on the etiology of severe thrombocytopenia during ECMO, as well as identifying indications and platelet thresholds for transfusion in the absence of bleeding., Trial Registration: This study was registered at the Netherlands Trial Registry at February 26th, 2020 with number NL8413 and can currently be found at https://trialsearch.who.int/Trial2.aspx?TrialID=NL8413., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO., Design: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications., Setting: Sixteen international ICUs., Patients: Adult patients on VA-ECMO or VV-ECMO., Interventions: None., Measurements and Main Results: Of 420 VA-ECMO patients, 59% ( n = 247) received plasma, 20% ( n = 82) received fibrinogen concentrate, 17% ( n = 70) received TXA, and 7% of patients ( n = 28) received PCC. Fifty percent of patients ( n = 208) suffered bleeding complications and 27% ( n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p < 0.001), fibrinogen concentrate (28% vs 11%, p < 0.001), and TXA (23% vs 10%, p < 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% ( n = 81) received plasma, 6% ( n = 12) fibrinogen concentrate, 7% ( n = 14) TXA, and 5% ( n = 10) PCC. Thirty-nine percent ( n = 80) of VV-ECMO patients suffered bleeding complications and 23% ( n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p < 0.001), fibrinogen concentrate (13% vs 2%, p < 0.01), and TXA (11% vs 2%, p < 0.01)., Conclusions: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided., Competing Interests: Dr. van der Velde received a speaker fee from Hamilton Medical. Author Marcella C.A. Müller received a speaker fee from Werfen. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: This study reports on survival and health related quality of life (HRQOL) after extracorporeal membrane oxygenation (ECMO) treatment and the associated costs in the first year., Materials and Methods: Prospective observational cohort study patients receiving ECMO in the intensive care unit during August 2017 and July 2019. We analyzed all healthcare costs in the first year after index admission. Follow-up included a HRQOL analysis using the EQ-5D-5L at 6 and 12 months., Results: The study enrolled 428 patients with an ECMO run during their critical care admission. The one-year mortality was 50%. Follow up was available for 124 patients at 12 months. Survivors reported a favorable mean HRQOL (utility) of 0.71 (scale 0-1) at 12 months of 0.77. The overall health status (VAS, scale 0-100) was reported as 73.6 at 12 months. Mean total costs during the first year were $204,513 ± 211,590 with hospital costs as the major factor contributing to the total costs. Follow up costs were $53,752 ± 65,051 and costs of absenteeism were $7317 ± 17,036., Conclusions: At one year after hospital admission requiring ECMO the health-related quality of life is favorable with substantial costs but considering the survival might be acceptable. However, our results are limited by loss of follow up. So it may be possible that only the best-recovered patients returned their questionnaires. This potential bias might lead to higher costs and worse HRQOL in a real-life scenario., Competing Interests: Declaration of Competing Interest Dirk W. Donker received speaker fee from Getinge-Maquet and Xenios NovaLung Fresenius. Dirk W. Donker has research cooperation's with Getinge-Maquet and Xenios NovaLung Fresenius. Roberto Lorusso is consultant for Medtronic, LivaNova, and Getinge. He is part of the Medical Advisory Board of Eurosets and Xenios. All honoraria are paid to the university for research funding. Dinis dos Reis Miranda received speaking fees from Xenios. The remaining authors have disclosed that they do not have any conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This scoping review aims to identify and describe knowledge gaps and research priorities in veno-arterial extracorporeal membrane oxygenation (VA-ECMO)., Methods: An expert panel was recruited consisting of eight international experts from different backgrounds. First, a list of priority topics was made. Second, the panel developed structured questions using population, intervention, comparison and outcomes (PICO) format. All PICOs were scored and prioritized. For every selected PICO, a structured literature search was performed., Results: After an initial list of 49 topics, eight were scored as high-priority. For most of these selected topics, current literature is limited to observational studies, mainly consisting of retrospective cohorts. Only for ECPR and anticoagulation, randomized controlled trials (RCTs) have been performed or are ongoing. Per topic, a summary of the literature is stated including recommendations for further research., Conclusions: This scoping review identifies and presents an overview of knowledge gaps and research priorities in VA-ECMO. Current literature is mostly limited to observational studies, although with increasing attention for this patient population, more RCTs are finishing or ongoing. Translational research, from preclinical trials to high-quality or randomized controlled trials, is important to improve the standard practices in this critically ill patient population. Take-home message This scoping review identifies and presents an overview of research gaps and priorities in VA-ECMO. Translational research, from preclinical trials to high-quality or randomized controlled trials, is important to improve the standard practices in this critically ill patient population., (© 2022. The Author(s).)

Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated., Objectives: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19-induced ARDS and to assess the possible impact of COVID-19 on mortality., Design Setting and Participants: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a "control" non-COVID ARDS cohort from January 2018 to July 2019., Main Outcomes and Measures: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19-related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables., Results: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19-associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27; 95% CI, 0.82-1.98; p = 0.30)., Conclusions and Relevance: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS., Competing Interests: Dr. Broman is a member of the Medical Advisory Boards of Eurosets Srl., Medolla, Italy, and Xenios AG, Heilbronn, Germany. Dr. Taccone is a member of the Medical Advisory Boards of Eurosets Srl., Medolla, Italy, and Xenios AG, Heilbronn, Germany. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS., Methods: All adult patients who were successfully weaned from ECLS and were screened for DVT following decannulation were included in this observational cohort study. The incidence of post-ECLS-DVT was assessed and the cannula-associated DVT rate was compared with that of patients without ECLS after central venous catheter (CVC) removal. The correlation between the level of anticoagulation, risk factors, and post-ECLS-DVT was determined., Results: We included 30 ECLS patients and 53 non-ECLS patients. DVT was found in 15 patients (50%) of which 10 patients had a DVT in a cannulated vein. No correlation between the level of anticoagulation and DVT was found. V-V ECLS mode was the only independent risk factor for post-ECLS-DVT (OR 5.5; 95%CI 1.16-26.41). We found no difference between the ECLS and non-ECLS cohorts regarding cannula-associated DVT rate (33% vs. 32%)., Conclusion: Post-ECLS-DVT is a common finding that occurs in half of all patients supported with ECLS. The incidence of cannula-associated DVT was equal to CVC-associated DVT in critically ill patients without ECLS. V-V ECLS was an independent risk factor for post-ECLS-DVT., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome., Methods: We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2-2.5 times baseline aPTT, 1.5-2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months., Discussion: We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO., Trial Registration: ClinicalTrials.gov NCT04536272 . Registered on 2 September 2020. Netherlands Trial Register NL7969., (© 2022. The Author(s).)

Objectives: Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding., Data Sources: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019)., Data Selection: Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events., Data Extraction: Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach., Data Synthesis: Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty., Conclusions: Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety., Competing Interests: Dr. Oczkowski received payment as a methodology consultant for the American Thoracic Society. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objectives: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation., Design: Mixed method approach combining multicenter retrospective study and survey., Setting: Sixteen ICUs worldwide., Patients: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019., Interventions: None., Measurements and Main Results: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients., Conclusions: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation., Competing Interests: Dr. Lorusso’s institution received funding from Medtronic, Livanova, Eurosets, and Getinge. Dr. Dos Reis Miranda’s institution received funding from Xenios. Dr. Donker receives speaker fees from Getinge-Maquet and Xenios NovaLung Fresenius and research cooperation with Getinge-Maquet and Xenios NovaLung Fresenius. Dr. Broman received funding from Eurosets and Xenios. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: To develop evidence-based clinical practice recommendations regarding transfusion practices and transfusion in bleeding critically ill adults., Methods: A taskforce involving 15 international experts and 2 methodologists used the GRADE approach to guideline development. The taskforce addressed three main topics: transfusion support in massively and non-massively bleeding critically ill patients (transfusion ratios, blood products, and point of care testing) and the use of tranexamic acid. The panel developed and answered structured guideline questions using population, intervention, comparison, and outcomes (PICO) format., Results: The taskforce generated 26 clinical practice recommendations (2 strong recommendations, 13 conditional recommendations, 11 no recommendation), and identified 10 PICOs with insufficient evidence to make a recommendation., Conclusions: This clinical practice guideline provides evidence-based recommendations for the management of massively and non-massively bleeding critically ill adult patients and identifies areas where further research is needed., (© 2021. The Author(s).)

Background: To report and compare the characteristics and outcomes of COVID-19 patients on extracorporeal membrane oxygenation (ECMO) to non-COVID-19 acute respiratory distress syndrome (ARDS) patients on ECMO., Methods: We performed an international retrospective study of COVID-19 patients on ECMO from 13 intensive care units from March 1 to April 30, 2020. Demographic data, ECMO characteristics and clinical outcomes were collected. The primary outcome was to assess the complication rate and 28-day mortality; the secondary outcome was to compare patient and ECMO characteristics between COVID-19 patients on ECMO and non-COVID-19 related ARDS patients on ECMO (non-COVID-19; January 1, 2018 until July 31, 2019)., Results: During the study period 71 COVID-19 patients received ECMO, mostly veno-venous, for a median duration of 13 days (IQR 7-20). ECMO was initiated at 5 days (IQR 3-10) following invasive mechanical ventilation. Median PaO 2 /FiO 2 ratio prior to initiation of ECMO was similar in COVID-19 patients (58 mmHg [IQR 46-76]) and non-COVID-19 patients (53 mmHg [IQR 44-66]), the latter consisting of 48 patients. 28-day mortality was 37% in COVID-19 patients and 27% in non-COVID-19 patients. However, Kaplan-Meier curves showed that after a 100-day follow-up this non-significant difference resolves. Non-surviving COVID-19 patients were more acidotic prior to initiation ECMO, had a shorter ECMO run and fewer received muscle paralysis compared to survivors., Conclusions: No significant differences in outcomes were found between COVID-19 patients on ECMO and non-COVID-19 ARDS patients on ECMO. This suggests that ECMO could be considered as a supportive therapy in case of refractory respiratory failure in COVID-19.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

Introduction: The aim of this study was to investigate the usefulness of ethyl glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state., Methods: Thirty-sixhealthy social drinkers participated in this study, being of naturalistic design. Eighteen participants experience regular hangovers (the hangover group), whereas the other 18 claim to not experience a hangover (the hangover-immune group). On a control day (alcohol-free) day and a post-alcohol day, urine EtG and EtS concentrations were determined and hangover severity assessed., Results: Urinary EtG and EtS concentrations were significantly increased on post-alcohol day compared to the control day (p = .0001). Both EtG and EtS concentrations did not significantly correlate with the overall hangover score, nor with the estimated peak blood alcohol concentrations and number of alcoholic drinks. EtG correlated significantly only with the individual hangover symptom "headache" (p = .033; r = .403). No significant correlations were found with the EtG to EtS ratio. EtG and EtS concentrations significantly correlated with urine ethanol concentrations., Conclusions: Although urine EtG and EtS concentration did not significantly correlate to estimated peak blood alcohol concentrations or the number of alcoholic drinks consumed, a significant correlation was found with urine ethanol concentration. However, urine EtG and EtS concentrations did not significantly correlate with overall hangover severity., (© 2017 The Authors. Human Psychopharmacology: Clinical & Experimental Published by John Wiley & Sons Ltd.)