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Background: The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the ECMO system, but this comes with an increased risk of bleeding. Evidence on the use of anti‐Xa‐guided monitoring to prevent bleeding during ECMO support is limited. Therefore, we aimed to analyze the association between anti‐factor Xa‐guided anticoagulation and hemorrhage during ECMO. Methods: A systematic review and meta‐analysis was performed (up to August 2023). PROSPERO: CRD42023448888. Results: Twenty‐six studies comprising 2293 patients were included in the analysis, with six works being part of the meta‐analysis. The mean anti‐Xa values did not show a significant difference between patients with and without hemorrhage (standardized mean difference −0.05; 95% confidence interval [CI]: −0.19; 0.28, p =.69). We found a positive correlation between anti‐Xa levels and unfractionated heparin dose (UFH; pooled estimate of correlation coefficients 0.44; 95% CI: 0.33; 0.55, p <.001). The most frequent complications were any type of hemorrhage (pooled 36%) and thrombosis (33%). Nearly half of the critically ill patients did not survive to hospital discharge (47%). Conclusions: The most appropriate tool for anticoagulation monitoring in ECMO patients is uncertain. Our analysis did not reveal a significant difference in anti‐Xa levels in patients with and without hemorrhagic events. However, we found a moderate correlation between anti‐Xa and the UFH dose, supporting its utilization in monitoring UFH anticoagulation. Given the limitations of time‐guided monitoring methods, the role of anti‐Xa is promising and further research is warranted. [ABSTRACT FROM AUTHOR]

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) can provide circulatory and respiratory support in patients with cardiogenic shock. The main aim of this work was to investigate the association of blood biomarkers with mortality in patients with myocardial infarction needing va-ECMO support. Methods: We retrospectively analyzed electronic medical charts from patients receiving va-ECMO support in the period from 2008 to 2021 at the Medical University Innsbruck, Department of Anesthesiology and Intensive Care Medicine. Results: Of 188 patients, 57% (108/188) survived to discharge, with hemorrhage (46%) and thrombosis (27%) as the most frequent adverse events. Procalcitonin levels were markedly higher in non-survivors compared with survivors during the observation period. The multivariable model identified higher blood levels of procalcitonin (HR 1.01, p = 0.002) as a laboratory parameter associated with a higher risk of mortality. Conclusions: In our study population of patients with myocardial infarction-associated cardiogenic shock, deceased patients had increased levels of inflammatory blood biomarkers throughout the whole study period. Increased procalcitonin levels have been associated with a higher risk of mortality. Future studies are needed to show the role of procalcitonin in patients receiving ECMO support. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation is a standard of care and a life-saving procedure for end-stage liver diseases and certain malignancies. The evidence on predictors and risk factors for poor outcomes is lacking. Therefore, we aimed to identify potential risk factors for mortality and to report on overall 90-day mortality after orthotopic liver transplantation (OLT), especially focusing on the role of fungal infections. Methods: We retrospectively reviewed medical charts of all patients undergoing OLT at a tertiary university center in Europe. Results: From 299 patients, 214 adult patients who received a first-time OLT were included. The OLT indication was mainly due to tumors (42%, 89/214) and cirrhosis (32%, 68/214), including acute liver failure in 4.7% (10/214) of patients. In total, 8% (17/214) of patients died within the first three months, with a median time to death of 15 (1–80) days. Despite a targeted antimycotic prophylaxis using echinocandins, invasive fungal infections occurred in 12% (26/214) of the patients. In the multivariate analysis, patients with invasive fungal infections had an almost five times higher chance of death (HR 4.6, 95% CI 1.1–18.8; p = 0.032). Conclusions: Short-term mortality after OLT is mainly determined by infectious and procedural complications. Fungal breakthrough infections are becoming a growing concern. Procedural, host, and fungal factors can contribute to a failure of prophylaxis. Finally, invasive fungal infections may be a potentially modifiable risk factor, but the ideal perioperative antimycotic prophylaxis has yet to be determined. [ABSTRACT FROM AUTHOR]

Background: The initiation of extracorporeal membrane oxygenation (ECMO) is associated with complex inflammatory and coagulatory processes, raising the need for systemic anticoagulation. The balance of anticoagulatory and procoagulant factors is essential, as therapeutic anticoagulation confers a further risk of potentially life-threatening bleeding. Therefore, our study aims to systematize and analyze the most recent evidence regarding anticoagulation monitoring and the thromboembolic events in patients receiving veno-arterial ECMO support. Methods: Using the PRISMA guidelines, we systematically searched the Scopus and PubMed databases up to October 2022. A weighted effects model was employed for the meta-analytic portion of the study. Results: Six studies comprising 1728 patients were included in the final analysis. Unfractionated heparin was used for anticoagulation, with an activated partial thromboplastin time (aPTT) monitoring goal set between 45 and 80 s. The majority of studies aimed to investigate the incidence of adverse events and potential risk factors for thromboembolic and bleeding events. None of the authors found any association of aPTT levels with the occurrence of thromboembolic events. Finally, the most frequent adverse events were hemorrhage (pooled 43%, 95% CI 28.4; 59.5) and any kind of thrombosis (pooled 36%, 95% CI 21.7; 53.7), and more than one-half of patients did not survive to discharge (pooled 54%). Conclusions: Despite the tremendous development of critical care, aPTT-guided systemic anticoagulation is still the standard monitoring tool. We did not find any association of aPTT levels with thrombosis. Further evidence and new trials should clarify the true incidence of thromboembolic events, along with the best anticoagulation and monitoring strategy in veno-arterial ECMO patients. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) are one of the most important infectious complications after liver transplantation, determining morbidity and mortality. Antimycotic prophylaxis may impede IFI, but a consensus on indication, agent, or duration is still missing. Therefore, this study aimed to investigate the incidence of IFIs under targeted echinocandin antimycotic prophylaxis in adult high-risk liver transplant recipients. We retrospectively reviewed all patients undergoing a deceased donor liver transplantation at the Medical University of Innsbruck in the period from 2017 to 2020. Of 299 patients, 224 met the inclusion criteria. We defined patients as being at high risk for IFI if they had two or more prespecified risk factors and these patients received prophylaxis. In total, 85% (190/224) of the patients were correctly classified according to the developed algorithm, being able to predict an IFI with a sensitivity of 89%. Although 83% (90/109) so defined high-risk recipients received echinocandin prophylaxis, 21% (23/109) still developed an IFI. The multivariate analysis identified the age of the recipient (hazard ratio—HR = 0.97, p = 0.027), split liver transplantation (HR = 5.18, p = 0.014), massive intraoperative blood transfusion (HR = 24.08, p = 0.004), donor-derived infection (HR = 9.70, p < 0.001), and relaparotomy (HR = 4.62, p = 0.003) as variables with increased hazard ratios for an IFI within 90 days. The fungal colonization at baseline, high-urgency transplantation, posttransplant dialysis, bile leak, and early transplantation showed significance only in a univariate model. Notably, 57% (12/21) of the invasive Candida infections were caused by a non-albicans species, entailing a markedly reduced one-year survival. The attributable 90-day mortality rate of an IFI after a liver transplant was 53% (9/17). None of the patients with invasive aspergillosis survived. Despite targeted echinocandin prophylaxis, there is still a notable risk for IFI. Consequently, the prophylactic use of echinocandins must be critically questioned regarding the high rate of breakthrough infections, the increased occurrence of fluconazole-resistant pathogens, and the higher mortality rate in non-albicans Candida species. Adherence to the internal prophylaxis algorithms is of immense importance, bearing in mind the high IFI rates in case algorithms are not followed. [ABSTRACT FROM AUTHOR]

Background: The use of extracorporeal membrane oxygenation (ECMO) for critically ill patients is growing rapidly given recent developments in technology. However, adverse events are frequently reported that have potentially devastating impacts on patient outcomes. The information on predictors and risk factors for thrombotic events, especially that focusing on the comparison of veno-arterial and veno-venous ECMO configurations, are still inconsistent and sparse; therefore, we aimed to close this gap. Methods: We performed a retrospective analysis of all patients on extracorporeal life support admitted to the intensive care units of a tertiary university center in Europe. Results: From 645 patients, 417 who received extracorporeal life support due to cardiogenic shock (290, 70%), respiratory failure (116, 28%) or hypothermia (11, 3%) were included. In total, 22% (92) of the patients experienced thrombotic events with a similar incidence in both ECMO configurations. Anticoagulation consisted of unfractionated heparin (296, 71%) and argatroban (70, 17%). Univariate Cox analyses identified hemoconcentration and increased maximal clot firmness (thromboelastometry) as risk factors for thrombosis. Moreover, the patients experiencing thrombosis had longer ECMO duration and intensive care stays. Conclusions: ECMO is a specialized life-support modality with a high risk of complications. A longer ECMO duration is associated with thrombosis occurrence in patients receiving ECMO support. Following hemorrhage, thromboembolic complications are common adverse events. However, in contrast to major bleeding, no impact on mortality was observed. The question arises if a protocol with less anticoagulation may have a role to play in the future. [ABSTRACT FROM AUTHOR]

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) is a temporary life support for severe cardiogenic shock, gaining time for organ recovery, permanent assistance, or transplantation. In this work, we aimed to investigate the trends of blood biomarkers over the period of ECMO support and their role in patient outcome. Methods: This retrospective study comprised patients receiving va-ECMO support over the period of 14 years at a tertiary university center. Results: Of 435 patients, 62% (268/435) survived to discharge, and the most frequent adverse event was hemorrhage (46%), followed by thrombosis (25%). Deceased patients had increased blood levels of C-reactive protein, procalcitonin, and white blood cells during the whole observation period, with higher peaks compared with survivors. The multivariable model identified hemorrhage (HR 1.73, p = 0.005) and higher levels of procalcitonin (HR 1.01, p = 0.001) as independent risk factors for death. Conclusions: In our population of critically ill patients receiving va-ECMO support, deceased patients had increased inflammatory biomarkers during the whole observation period. Patients having higher values of procalcitonin and experiencing bleeding events showed an increased risk for mortality. Further studies focusing on inflammation in ECMO patients, clarifying its role in patient outcome and potential therapeutic interventions, are warranted. [ABSTRACT FROM AUTHOR]

Background: Veno-arterial extracorporeal membrane oxygenation (va-ECMO) is a specialized temporary support for patients with refractory cardiogenic shock. The true value of this potentially lifesaving modality is still a subject of debate. Therefore, we aimed to investigate the overall in-hospital mortality and identify potential risk factors for mortality. Methods: We retrospectively analyzed the data of 453 patients supported with va-ECMO over a period of 14 years who were admitted to intensive care units of a tertiary university center in Austria. Results: We observed in-hospital mortality of 40% for patients with refractory cardiogenic shock. Hemorrhage, ECMO initiation on weekends, higher SAPS III score, and sepsis were identified as significant risk factors for mortality. Hemorrhage was the most common adverse event (46%), with major bleeding events dominating in deceased patients. Thromboembolic events occurred in 25% of patients, followed by sepsis (18%). Conclusions: Although the rates of complications are substantial, a well-selected proportion of patients with refractory cardiogenic shock can be rescued from probable death. The reported risk factors could be used to increase the awareness of clinicians towards the development of new therapeutic concepts that may reduce their incidence. [ABSTRACT FROM AUTHOR]

The development of extracorporeal life support technology has added a new dimension to the care of critically ill patients who fail conventional treatment options. Extracorporeal membrane oxygenation (ECMO)—specialized temporary life support for patients with severe cardiac or pulmonary failure—plays a role in bridging the time for organ recovery, transplant, or permanent assistance. The overall patient outcome is dependent on the underlying disease, comorbidities, patient reaction to critical illness, and potential adverse events during ECMO. Moreover, the contact of the blood with the large artificial surface of an extracorporeal system circuit triggers complex inflammatory and coagulation responses. These processes may further lead to endothelial injury and disrupted microcirculation with consequent end-organ dysfunction and the development of adverse events like thromboembolism. Therefore, systemic anticoagulation is considered crucial to alleviate the risk of thrombosis and failure of ECMO circuit components. The gold standard and most used anticoagulant during extracorporeal life support is unfractionated heparin, with all its benefits and disadvantages. However, therapeutic anticoagulation of a critically ill patient carries the risk of clinically relevant bleeding with the potential for permanent injury or death. Similarly, thrombotic events may occur. Therefore, different anticoagulation strategies are employed, while the monitoring and the balance of procoagulant and anticoagulatory factors is of immense importance. This narrative review summarizes the most recent considerations on anticoagulation during ECMO support, with a special focus on anticoagulation monitoring and future directions. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) is a specialised life support modality for patients with refractory cardiac or respiratory failure. Multiple studies strived to evaluate the benefits of ECMO support, but its efficacy remains controversial with still inconsistent and sparse information. Methods: This retrospective analysis included patients with ECMO support, admitted between January 2010 and December 2019 at a tertiary university ECMO referral centre in Austria. The primary endpoint of the study was overall all-cause three-month mortality with risk factors and predictors of mortality. Secondary endpoints covered the analysis of demographic and clinical characteristics of patients needing ECMO, including incidence and type of adverse events during support. Results: In total, 358 patients fulfilled inclusion criteria and received ECMO support due to cardiogenic shock (258, 72%), respiratory failure (88, 25%) or hypothermia (12, 3%). In total, 41% (145) of patients died within the first three months, with the median time to death of 9 (1–87) days. The multivariate analysis identified hypothermia (HR 3.8, p < 0.001), the Simplified Acute Physiology Score III (HR 1.0, p < 0.001), ECMO initiation on weekends (HR 1.6, p = 0.016) and haemorrhage during ECMO support (HR 1.7, p = 0.001) as factors with higher risk for mortality. Finally, the most frequent adverse event was haemorrhage (160, 45%) followed by thrombosis. Conclusions: ECMO is an invasive advanced support system with a high risk of complications. Nevertheless, well-selected patients can be successfully rescued from life-threatening conditions by prolonging the therapeutic window to either solve the underlying problem or install a long-term assist device. Hypothermia, disease severity, initiation on weekends and haemorrhage during ECMO support increase the risk for mortality. In the case of decision making in a setting of limited (ICU) resources, the reported risk factors for mortality may be contemplable, especially when judging a possible ECMO support termination. [ABSTRACT FROM AUTHOR]