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Background: Low T3-(/T4-) syndrome, also known as non-thyroidal Illness Syndrome (NTIS) describes a decrease in free serum thyroid hormones without a concomitant increase in TSH, frequently observed in critically ill patients. However, whether NTIS is only a metabolic adaption to stress in critically ill or plays a crucial role as an independent risk factor for ICU mortality, remains unknown. Our study aimed to evaluate NTIS as an independent risk factor for increased ICU mortality., Methods: All patients admitted to the interdisciplinary intensive care unit (ICU) at the University Hospital of Leipzig between 2008 and 2014 were retrospectively analyzed for thyroidal function. Baseline data, information on additional thyroid function tests, disease progression, hospital and ICU length of stay (LOS) and patient outcome were retrospectively analyzed from the hospitals digital information system. For statistical evaluation, univariate analysis, matched pairs analysis and multivariate logistic regression were conducted., Results: One thousand, seven hundred ninety patients were enrolled in the study, of which 665 showed NTIS. Univariate analysis revealed a positive association of NTIS with ICU- and hospital-LOS, need for mechanical ventilation, incidence of sepsis, acute respiratory distress syndrome, acute liver failure and increased ICU mortality. Results of matched pair analysis confirmed these findings. In multivariate logistic regression, NTIS was associated with an increased ICU-LOS, increased duration of mechanical ventilation, acute kidney injury and liver failure, but showed no independent association with increased ICU-mortality., Conclusion: Duration of mechanical ventilation as well as incidence of acute kidney injury, sepsis and acute liver failure were detected as independent predictors of mortality in patients with NTIS. NTIS itself was no independent predictor of increased ICU-mortality., (© 2023. The Author(s).)

Background: Recent data suggest that anesthesiologic interventions-e.g., the choice of the anesthetic regimen or the administration of blood products-might play a major role in determining outcome after tumor surgery. In contrast to adult patients, only limited data are available regarding the potential association of anesthesia and outcome in pediatric cancer patients., Methods: A retrospective multicenter study assessing data from pediatric patients (0-18 years of age) undergoing surgery for nephroblastoma between 2004 and 2018 was conducted at three academic centers in Europe. Overall and recurrence-free survival were the primary outcomes of the study and were evaluated for a potential impact of intraoperative administration of erythrocyte concentrates, the use of regional anesthesia and the choice of the anesthetic regimen. The length of stay on the intensive care unit, the time to hospital discharge after surgery and blood neutrophil-to-lymphocyte ratio were defined as secondary outcomes., Results: In total, data from 65 patients were analyzed. Intraoperative administration of erythrocyte concentrates was associated with a reduction in recurrence-free survival (hazard ratio (HR) 7.59, 95% confidence interval (CI) 1.36-42.2, p = 0.004), whereas overall survival (HR 5.37, 95% CI 0.42-68.4, p = 0.124) was not affected. The use of regional anesthesia and the choice of anesthetic used for maintenance of anesthesia did not demonstrate an effect on the primary outcomes. It was, however, associated with fewer ICU transfers, a shortened time to discharge and a decreased postoperative neutrophil-to-lymphocyte ratio., Conclusions: The current study provides the first evidence for a possible association between blood transfusion as well as anesthesiologic interventions and outcome after pediatric cancer surgery.

Aims: Septic cardiomyopathy is a severe complication of sepsis and septic shock. This study aimed to evaluate the role of thrombomodulin and its lectin-like domain (LLD-TM) in the development of septic cardiomyopathy and the link between LLD-TM, HMGB-1, and toll-like receptors 2/4 (TLR 2/4) to intracellular mechanisms resulting in reduced cardiac function., Materials and Methods: Sepsis was induced using a polymicrobial peritoneal infection model in wildtype and mice lacking the lectin-like domain of thrombomodulin (TM LeD/LeD ), and severity of disease and cardiac function was compared. Cell cultures of cardiomyocytes were prepared from hearts harvested from wildtype and TM LeD/LeD mice. Cultures of neonatal cardiomyocytes were transfected with complete human thrombomodulin or human thrombomodulin deficient of LLD-TM and when TLR-2 and/or TLR-4 were blocked. All cultures were challenged with inflammatory stimuli., Key Findings: Lack of the LLD-TM results in a significant increase in severity of disease, decreased survival and impaired cardiac function in septic mice. In vivo and in vitro analyses of cardiomyocytes displayed high levels of inflammatory cytokines causing cardio-depression. In vitro results showed a strong correlation between elevated HMGB-1 levels and elevated troponin-1 levels. No connection was found between HMGB-1 and TLR-2 and/or -4 signalling pathways. Phospholamban mediated dysregulation of calcium homeostasis resulted in a general impairment after sepsis induction, but showed no connection to LLD-TM., Significance: Lack of LLD-TM results in an increase in general severity of disease, decreased survival and impaired cardiac function in sepsis. TLR-2 and TLR 4 do not participate as mediating factors in the development of septic cardiomyopathy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Cachexia and nutritional problems play a major role in palliative care. Artificial nutrition such as parenteral nutrition is common but its role and indications in terminal patients remain controversial due to lack of data. Therefore, recommendations are vague. Benefits and risks of parenteral nutrition in palliative care as well as the clinical implementation of the guidelines have not been adequately studied yet., Methods: In this single-centre observational study, 72 palliative care patients were followed for 1 month. Patients with and without parenteral nutrition were analysed regarding venous access complications, oedema, weight and health-related quality of life., Results: 93% of all patients showed reduced food intake. 34 (47%) patients received parenteral nutrition. Parenteral nutrition reduced energy deficit but was not associated with quality of life. Complications with the venous accesses for parenteral nutrition were frequent. A relevant proportion of patients with planned parenteral nutrition received no or only a few days of parenteral nutrition. Moreover, patients with parenteral nutrition showed more frequent and pronounced oedema., Conclusion: The benefit-risk balance of palliative parenteral nutrition in end-of-life treatment seems to be questionable. In view of the identified risks, parenteral nutrition in end-of-life care should be initiated with caution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas−kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed. The primary study outcome was the detection of occurrence of early pancreatic graft dysfunction (ePGD), the secondary study outcome was early renal graft dysfunction (eRGD) as well as all other outcome parameters associated with the graft function. In this context, ePGD was defined as pancreas graft-related complications including graft pancreatitis, pancreatic abscess/peritonitis, delayed graft function, graft thrombosis, bleeding, rejection and the consecutive need for re-laparotomy due to graft-related complications within 3 months. With regard to analyzing ePGD, serum levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), pancreatic lipase as well as neutrophil−lymphocyte ratio (NLR) and platelet−lymphocyte ratio (PLR) were measured preoperatively and at postoperative days (POD) 1, 2, 3 and 5. Further, peak serum levels of CRP and lipase during the first 72 h were evaluated. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for ePGD and eRGD. Cut-off levels were calculated with the Youden index. Significant diagnostic biochemical cut-offs as well as other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 105 patients included, 43 patients (41%) and 28 patients (27%) developed ePGD and eRGD following SPKT, respectively. The mean WBC, PCT, NLR, PLR, CRP and lipase levels were significantly higher on most PODs in the ePGD group compared to the non-ePGD group. ROC analysis indicated that peak lipase (AUC: 0.82) and peak CRP levels (AUC: 0.89) were highly predictive for ePGD after SPKT. The combination of both achieved the highest AUC (0.92; p < 0.01) in predicting ePGD. Concerning eRGD, predictive accuracy of all analyzed serological markers was moderate (all AUC < 0.8). Additionally, multivariable analysis identified previous dialysis/no preemptive transplantation (OR 2.4 (95% CI: 1.41−4.01), p = 0.021), donor age (OR 1.07 (95% CI: 1.03−1.14), p < 0.010), donor body mass index (OR 1.32 (95% CI: 1.01−1.072), p = 0.04), donors cerebrovascular cause of death (OR 7.8 (95% CI: 2.21−26.9), p < 0.010), donor length of ICU stay (OR 1.27 (95% CI: 1.08−1.49), p < 0.010), as well as CIT pancreas (OR 1.07 (95% CI: 1.03−1.14), p < 0.010) as clinical relevant prognostic predictors for ePGD. Further, a peak of lipase (OR 1.04 (95% CI: 1.02−1.07), p < 0.010), peak of CRP levels (OR 1.12 (95% CI: 1.02−1.23), p < 0.010), pancreatic serum lipase concentration on POD 2 > 150 IU/L (OR 2.9 (95% CI: 1.2−7.13), p = 0.021) and CRP levels of ≥ 180 ng/mL on POD 2 (OR 3.6 (95% CI: 1.54−8.34), p < 0.01) and CRP levels > 150 ng/mL on POD 3 (OR 4.5 (95% CI: 1.7−11.4), p < 0.01) were revealed as independent biochemical predictive variables for ePGD after transplantation. Conclusions: In the current study, the combination of peak lipase and CRP levels were highly effective in predicting early pancreatic graft dysfunction development following SPKT. In contrast, for early renal graft dysfunction the predictive value of this parameter was less sensitive. Intensified monitoring of these parameters may be helpful for identifying patients at a higher risk of pancreatic ischemia reperfusion injury and various IRI- associated postoperative complications leading to ePGD and thus deteriorated outcome.

Perfluorocarbons are oxygen-carrying, dense liquids initially intended for the use in partial or total liquid ventilation of patients with severe acute respiratory distress syndrome but which did not show beneficial effects in clinical studies. However, perfluorocarbons may be used for lung lavage in severe alveolar proteinosis. In acute respiratory distress syndrome, oxygenation may be so severely compromised that the use of nonoxygenated perfluorocarbons may not be possible. We report a case of severe, nonresolving acute respiratory distress syndrome treated with extracorporeal membrane oxygenation to secure oxygenation, using perfluorocarbon in a single instillation to aid the clearance of debris and proteinacous edema., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Extracorporeal Membrane Oxygenation (ECMO) use is increasing despite limited evidence. The aim of this study was to demonstrate heterogeneity of ECMO use and its association with hospital size and annual frequency in Germany., Methods: This is a database analysis of all ECMO cases in Germany from 2010 to 2016 using the German Diagnosis Related Groups (DRG) coding system for ECMO., Results: During the study period, 510 hospitals performed 29,929 ECMO runs (12,572 vvECMO, 11,504 vaECMO, 1993 pECLA) with an increase over time. Mortality ranged between 58% and 66% for vaECMO cases and 66% and 53% for vvECMO cases. 304 (61%) hospitals performed only one ECMO per year. 78%% of all ECMO runs were performed in centres with more than 20 cases per year and more than half of all ECMO runs were performed in hospitals with >1.000 beds. Mortality for vv and vaECMO was highest in very small hospitals (< 200 beds; 70%; 74%) and very large hospitals (>1000 beds; 60%; 62%)., Conclusions: Use of ECMO is still increasing and a substantial proportion of hospitals performs very few ECMO runs. Small hospitals had a significantly higher mortality, but dependence on hospital size and ECMO mortality was irregular., Competing Interests: The authors have declared that no competing interests exist.

Transfusions of blood and blood products are live-saving, but complications may be fatal. Transfusion related lung injury (TRALI) is rare and pathophysiology not yet entirely understood. Diagnosis is difficult due to the usually life-threatening circumstances associated with transfusions and underlying diseases. In this mini-review article, we introduce two cases of TRALI to discuss the problems and controversies associated with different definitions, epidemiology, pathophysiology, blood products, diagnosis, and treatment. Future directions in the field are highlighted., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare

Introduction: Hemoglobin-based oxygen carriers (HBOC) have been developed as an alternative to blood transfusions. Their nitric-oxide-scavenging properties HBOC also induce vasoconstriction. In acute lung injury, an excess of nitric oxide results in a general vasodilation, reducing oxygenation by impairing the hypoxic pulmonary vasoconstriction. Inhaled nitric oxide (iNO) is used to correct the ventilation perfusion mismatch. We hypothesized that the additional use of HBOC might increase this effect. In a rodent model of ARDS we evaluated the combined effect of HBOC and iNO on vascular tone and gas exchange., Methods: ARDS was induced in anaesthetized Wistar rats by saline lavage and aggressive ventilation. Two groups received either hydroxyethylstarch 10% (HES; n = 10) or the HBOC hemoglobin glutamer-200 (HBOC-200; n = 10) via a central venous infusion. Additionally, both groups received iNO. Monitoring of the right ventricular pressure (RVP) and mean arterial pressure (MAP) was performed with microtip transducers. Arterial oxygenation was measured via arterial blood gas analyses., Results: Application of HBOC-200 led to a significant increase of MAP and RVP when compared to baseline and to the HES group. This effect was reversed by iNO. The application of HBOC and iNO had no effect on the arterial oxygenation over time. No difference in arterial oxygenation was found between the groups., Conclusion: Application of HBOC led to an increase of systemic and pulmonary vascular resistance in this animal model of ARDS. The increase in RVP was reversed by iNO. Pulmonary vasoconstriction by hemoglobin glutamer-200 in combination with iNO did not improve arterial oxygenation in ARDS., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In patients with severely compromised gas exchange, interhospital transportation is frequently necessary due to the need to provide access to specialized care. Risks are inherent during transport, so the anticipated benefits of transportation must be weighed against the possible negative outcome during the transport. The use of specialized teams during transportation can help to reduce adverse events. Diligent planning of the transportation, monitoring and medical staff during transport can decrease adverse events and reduce risks. This article defines the group of patients that may benefit from referral. This article discusses the risks associated with the transportation of patients with severely impaired gas exchange and the risks related to different means of transportation. The decisions required before transportation are described as well as the practical approach starting at the transferring hospital until arrival at the admitting hospital.

Background: The modalities of tracheostomy for critically ill patients are still controversially discussed. Although the use of percutaneous dilatational tracheostomy (PDT) is generally accepted to be a safe procedure, it is still not considered to be suitable for patients requiring a permanent tracheostomy., Methods: This was an observational cohort study investigating long-term outcome parameters of PDT. All patients having received a PDT at the interdisciplinary ICU at the University of Leipzig between October 2008 and August 2009 that survived to discharge were asked for consent to participate ( n = 103). Baseline data, admitting diagnosis, reasons for tracheostomy, and timing for tracheostomy were recorded. Subjects and medical providers were asked for neurological outcome, adverse events, and personal discomfort related to the tracheostomy. The study period was 2 y from the time of tracheostomy., Results: Seventy-one subjects were finally included in the survey. Data of 8 subjects (11%) were incomplete. Reasons for tracheostomy were the need for long-term ventilation (42%), weaning (31%), and neurological deficits (27%). No severe adverse events were registered. Sixty-five percent of all subjects could finally be decannulated. Two subjects remained with their initial tracheostomy, and in 5 subjects (7%) tracheostomy was modified to a surgical tracheostomy. Thirty-seven percent of subjects died during the 2 y. Twenty-five of the surviving subjects (35%) had only minor or moderate neurological and psychological deficits. Complaints were mostly connected to swallowing and breathing., Conclusions: Decannulations after PDT are easily done. Complications after PDT requiring a transformation to a surgical tracheostomy are rare. Elective surgical conversions are not necessary., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

Background: Prone positioning of patients with acute respiratory distress syndrome (ARDS) has been shown to significantly improve survival rates. Prone positioning reduces collapse of dorsal lung segments with subsequent reduction of alveolar overdistension of ventral lung segments, optimizes lung recruitment and enhances drainage. Patients with ARDS treated by extracorporeal membrane oxygenation (ECMO) can also benefit from prone positioning; however, the procedure is associated with a possible higher risk of serious adverse events., Objective: The aim of this study was to evaluate the safety and feasibility of prone positioning for patients with severe ARDS during ECMO therapy., Material and Methods: This study involved a retrospective analysis of all patients placed in a prone position while being treated by venovenous ECMO (vvECMO) for severe hypoxemia in ARDS as bridge to recovery in the interdisciplinary intensive care unit at the University Hospital Leipzig between January 2009 and August 2013. Baseline data, hospital mortality and serious adverse events were documented. Serious adverse events were defined as dislocation or obstruction of endotracheal tube or tracheal cannula, ECMO cannulas and cardiac arrest. Prone positioning was carried out by at least one doctor and three nurses according to a standardized protocol. Results are given as the median (1st and 3rd quartiles)., Results: A total of 26 patients were treated with vvECMO as bridge to recovery due to severe ARDS. Causes for ARDS were pneumonia (n = 20) and aspiration (n = 2) and four patients had different rare causes of ARDS. The median time on ECMO was 8 days (6;11) and during this period 134 turning events were documented. Patients were proned for a median of 5 (3;7) periods with a median duration of 12 h (8;12). No serious adverse events were recorded. The hospital mortality was 42% and mortality during the ECMO procedure was 35%., Conclusion: Prone positioning significantly reduces the mortality of patients with severe ARDS. In this series of 26 patients with severe ARDS during ECMO therapy no serious adverse events were found during the use of prone positioning.

Background: Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it's biochemical mechanisms and effects on inflammatory reactions., Methods: Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO2 = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured., Results: HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3(rd) and 6(th) hour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines., Conclusion: Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials., (Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The aim of the present study was to characterize a murine model of acute respiratory distress syndrome (ARDS) abiding by the Berlin definition of human ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline injection at both time points. Haemodynamics were monitored continuously. Arterial blood gas analyses were performed just before and every 30 min after OA challenge. Ninety minutes after OA challenge, the chest of mice was scanned using micro-computed tomography (CT). Cytokine concentrations were measured in plasma samples. Lungs were harvested 90 min after OA challenge for histology, immunohistochemistry, lung weight measurements and tissue cytokine detection. A histological lung injury score was determined. Eighteen hours after LPS challenge, mice exhibited a severe systemic inflammatory response syndrome. Oxygenation declined significantly after OA injections (Pa o2 /Fi o2 283 ± 73 and 256 ± 71 mmHg at 60 and 90 min, respectively; P < 0.001). Bilateral patchy infiltrates were present on the micro-CT scans. Histology revealed parenchymal damage with accumulation of polymorphonuclear neutrophils, intra-alveolar proteinacous debris and few hyaline membranes. The lung wet : dry ratio indicated damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe local and systemic inflammatory state in plasma and lung tissue. In conclusion, the described two-hit model of ARDS shows a pathological picture of ARDS closely mimicking human ARDS according to the Berlin definition and may facilitate interpretation of prospective experimental results., (© 2014 Wiley Publishing Asia Pty Ltd.)

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Perfluorocarbons (PFCs) are organic liquids derived from hydrocarbons in which some of the hydrogen atoms have been replaced by fluorine atoms. They are chemically and biologically inert substances with a good safety profile. They are stable at room temperature, easy to store, and immiscible in water. Perfluorocarbons have been studied in biomedical research since 1960 for their unique properties as oxygen carriers. In particular, PFCs have been used for liquid ventilation in unusual environments such as deep-sea diving and simulations of zero gravity, and more recently for drug delivery and diagnostic imaging. Additionally, when delivered as emulsions, PFCs have been used as red blood cell substitutes. This narrative review will discuss the multifaceted utilization of PFCs in therapeutics, diagnostics, and research. We will specifically emphasize the potential role of PFCs as red blood cell substitutes, as airway mechanotransducers during artificial placenta procedures, as a means to improve donor organ perfusion during the ex vivo assessment, and as an adjunct in cancer therapies because of their ability to reduce local tissue hypoxia., Competing Interests: Disclosure: M.D.N. is an advisory board member for Eurosets, Medolla Modena, Italy. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

This retrospective cohort study aimed to compare blood component transfusion before and after the implementation of a restrictive transfusion strategy (RTS) in pediatric cardiac Extracorporeal Life Support (ECLS) patients. The study included children admitted to the pediatric cardiac intensive care unit (PCICU) at the Stollery Children's Hospital who received ECLS between 2012 and 2020. Children on ECLS between 2012 and 2016 were treated with standard transfusion strategy (STS), while those on ECLS between 2016 and 2020 were treated with RTS. During the study, 203 children received ECLS. Daily median (interquartile range [IQR]) packed red blood cell (PRBC) transfusion volume was significantly lower in the RTS group; 26.0 (14.4-41.5) vs. 41.5 (26.6-64.4) ml/kg/day, p value <0.001. The implementation of a RTS led to a median reduction of PRBC transfusion of 14.5 (95% CI: 6.70-21.0) ml/kg/day. Similarly, the RTS group received less platelets: median (IQR) 8.4 (4.50-15.0) vs. 17.5 (9.40-29.0) ml/kg/day, p value <0.001. The implementation of a RTS resulted in a median reduction of platelet transfusion of 9.2 (95% CI: 5.45-13.1) ml/kg/day. The RTS resulted in less median (IQR) fluid accumulation in the first 48 hours: 56.7 (2.30-121.0) vs. 140.4 (33.8-346.2) ml/kg, p value = 0.001. There were no significant differences in mechanical ventilation days, PCICU/hospital days, or survival. The use of RTS resulted in lower blood transfusion volumes, with similar clinical outcomes., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Abstract: This study aimed to explore the ameliorating effects of the platelet surface glycoprotein IIb/IIIa receptor antagonist tirofiban on coagulation and fibrinolytic abnormalities in a mouse model of antibody-mediated transfusion-associated acute lung injury (ALI). This is important because ALI is a major cause of death attributable to the occurrence of adverse transfusion reactions. No information on a definite diagnosis or pathological mechanism exists, and targeted treatment options are not available. In this study, wild-type male Balb/c mice aged 8 to 10 weeks were randomly divided into the TRALI model, blank control, tirofiban intervention, and isotype control groups. After different treatment exposures, the mice were observed for 2 h before being killed, and lung tissue samples were collected. To explore the intervention effect of tirofiban, the degree of lung injury was quantified by estimating the lung wet/dry ratio, rectal temperature, survival rate, total protein, and myeloperoxidase and via hematoxylin-eosin staining. Furthermore, the coagulation, anticoagulation, and fibrinolysis assays were measured by automatic coagulation instrument and enzyme-linked immunosorbent assay kits, and the fluorescence densities of platelets and fibrin were quantified using immunofluorescence to analyze the effects of tirofiban on the platelet and fibrin interactions of TRALI. Compared with the TRALI model group, the lung injury indices in the tirofiban intervention group decreased significantly, and survival rates also improved. Furthermore, the level of coagulation and fibrinolytic abnormalities were obviously lower than those in the TRALI model group. In conclusion, our findings suggest that tirofiban might interfere with TRALI by inhibiting platelet activation and improving coagulation and fibrinolytic abnormalities., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) is used to achieve oxygenation and protect lung ventilation. Near infrared spectroscopy (NIRS) measures cerebral regional tissue oxygenation (rSO 2 ) and may contribute to patient safety during interhospital transport under ECMO support. We evaluated 16 adult ARDS patients undergoing interhospital ECMO transport by measuring cerebral rSO 2 before and after initiation of ECMO support and continuously during transport. To compare peripheral oxygen saturation (SpO 2 ) measurement with rSO 2 , both parameters were analyzed. NIRS monitoring for initiation of ECMO and interhospital transport under ECMO support was feasible, and there was no significant difference in the percentage of achievable valid measurements over time between cerebral rSO 2 (88.4% [95% confidence interval {CI}, 81.3-95.0%]) and standard SpO 2 monitoring 91.7% (95% CI, 86.1-94.2%), p = 0.68. No change in cerebral rSO 2 was observed before 77% (73.5-81%) (median [interquartile range {IQR}]) and after initiation of ECMO support 78% (75-81%), p = 0.2. NIRS for cerebral rSO 2 measurement is feasible during ECMO initiation and interhospital transport. Achievement of valid measurements of cerebral rSO 2 was not superior to SpO 2 . In distinct patients ( e.g. , shock), measurement of cerebral rSO 2 may contribute to improvement of patient safety during interhospital ECMO transport., Competing Interests: Disclosure: J.C.S. and T.M. have received lecture honoraria and travel grants from Maquet Getinge, Germany. S.S. has received travel support from Maquet Getinge, Germany. All other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Blood product transfusions are necessary for critically ill neonates on extracorporeal membrane oxygenation (ECMO). Transfusions are administered in response to unstudied arbitrary thresholds and may be associated with adverse outcomes. The objective of this study was to identify relationships between blood product components and mortality in neonates receiving ECMO support for respiratory indications., Study Design and Methods: A retrospective review of neonates receiving ECMO for respiratory indications from 2002 to 2019 from a single quaternary-referral neonatal intensive care unit (NICU). Demographic and outcome data and transfusion volume (ml/kg/day) were harvested from the medical record, and baseline mortality risk was assessed using NEO-RESCUERS scores. The association between volume of red blood cells (RBC), platelet, plasma transfusion rates (ml/kg/day), and mortality on ECMO were assessed after adjustment for NEO-RESCUERS score. Cox proportional hazards (CPH) competing risk model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and mortality outcome., Measurements and Main Results: Among 248 neonates undergoing ECMO for respiratory failure, overall survival was 93%. RBC, platelet, and plasma volume were highly associated with mortality during ECMO in an unadjusted model. After adjusting for NEO-RESCUERS score, RBC volume was associated with increased mortality risk (HR 1.013, 95% CI 1.004-1.022, p = .0043), but platelet and plasma volume were not associated with mortality., Conclusions: RBC, but not platelet or plasma volume, is associated with mortality in neonates on ECMO. Our findings refute previous studies demonstrating an association between platelet volume and mortality for neonates on ECMO., (© 2022 AABB.)

Extracorporeal membrane oxygenation (ECMO) is increasingly being used for patients with severe respiratory failure and has received particular attention during the coronavirus disease 2019 (COVID-19) pandemic. Evidence from two key randomized controlled trials, a subsequent post hoc Bayesian analysis, and meta-analyses support the interpretation of a benefit of ECMO in combination with ultra-lung-protective ventilation for select patients with very severe forms of acute respiratory distress syndrome (ARDS). During the pandemic, new evidence has emerged helping to better define the role of ECMO for patients with COVID-19. Results from large cohorts suggest outcomes during the first wave of the pandemic were similar to those in non-COVID-19 cohorts. As the pandemic continued, mortality of patients supported with ECMO has increased. However, the precise reasons for this observation are unclear. Known risk factors for mortality in COVID-19 and non-COVID-19 patients are higher patient age, concomitant extra-pulmonary organ failures or malignancies, prolonged mechanical ventilation before ECMO, less experienced treatment teams and lower ECMO caseloads in the treating center. ECMO is a high resource-dependent support option; therefore, it should be used judiciously, and its availability may need to be constrained when resources are scarce. More evidence from high-quality research is required to better define the role and limitations of ECMO in patients with severe COVID-19., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Bleeding remains a major source of morbidity associated with veno-venous extracorporeal membrane oxygenation (VV-ECMO). Moreover, there remains significant controversy, and a paucity of data regarding the ideal anticoagulation strategy for VV-ECMO patients. All patients undergoing isolated, peripheral VV-ECMO between January 2009 and December 2014 at our institution were retrospectively reviewed. Patients (n = 123) were stratified into one of three sequential eras of anticoagulation strategies: activated clotting time (ACT: 160-180 seconds, n = 53), high-partial thromboplastin time (H-PTT: 60-80 seconds, n = 25), and low-PTT (L-PTT: 45-55 seconds, n = 25) with high-flow (>4 L/min). Pre-ECMO APACHE II scores, SOFA scores, and Murray scores were not significantly different between the groups. Patients in the L-PTT group required less red blood cell units on ECMO than the ACT or H-PTT group (2.1 vs. 1.3 vs. 0.9; p < 0.001) and patients in the H-PTT and L-PTT group required less fresh frozen plasma than the ACT group (0.33 vs. 0 vs. 0; p = 0.006). Overall, major bleeding events were significantly lower in the L-PTT group than in the ACT and H-PTT groups. There was no difference in thrombotic events. In this single-institution experience, a L-PTT, high-flow strategy on VV-ECMO was associated with fewer bleeding and no difference in thrombotic events than an ACT or H-PTT strategy., Competing Interests: The authors report no conflicts of interest related to this manuscript. No funding was required for this study., (Copyright © ASAIO 2021.)

Use of extracorporeal membrane oxygenation (ECMO) is increasing among critically ill adults with cardiac and/or respiratory failure. Use of ECMO is associated with hemostatic alterations requiring use of anticoagulation and blood product support. There are limited guidelines to direct transfusion management in the adult patient supported with ECMO. The objective of this article is to describe (1) the role of the transfusion service in providing transfusion support and current understanding of transfusion thresholds, (2) the complexities of monitoring anticoagulation, and (3) the consideration regarding additional factor concentrates and antifibrinolytics within the context of ECMO support. The information provided should assist ECMO care teams in informing transfusion and anticoagulation practice while highlighting key areas for future research and collaboration., (© 2022 AABB.)