Anti-Xa-guided Anticoagulation With Unfractionated Heparin and Thrombosis During Extracorporeal Membrane Oxygenation Support: A Systematic Review and Meta-analysis.

OBJECTIVE: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support. DESIGN: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023). SETTING: All retrospective and prospective studies. PARTICIPANTS: Patients receiving ECMO support. INTERVENTION: Anticoagulation monitoring during ECMO support. MEASUREMENTS AND MAIN RESULTS: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%). CONCLUSIONS: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support.

[Quality of life after in-hospital cardiac arrest : An 11-year experience from an university center]. / Lebensqualität nach innerklinischem Herz-Kreislauf-Stillstand : 11-Jahres-Ergebnisse einer Universitätsklinik.

BACKGROUND: Cardiac arrest is a life-threatening condition requiring urgent medical care and is one of the leading causes of death worldwide. Given that in-hospital cardiac arrest (IHCA) is still poorly investigated, data on health-associated quality of life thereafter remains scarce. The available evidence is mostly transferred from out-of-hospital cardiac arrest studies, but the epidemiology and determinants of success might be different. The aim of the study was to investigate the change in the quality of life after in-hospital cardiac arrest and to identify potential risk factors for a poor outcome. MATERIAL AND METHODS: This retrospective analysis of data and prospective evaluation of quality of life included all patients surviving an IHCA and being treated by the emergency medical team between 2010 and 2020. The primary endpoint of the study was the quality of life after IHCA at the reference date. Secondary endpoints covered determination of risk factors and predictors of poor outcome after in-hospital cardiopulmonary resuscitation. RESULTS: In total 604 patients were resuscitated within the period of 11 years and 61 (10%) patients survived until the interview took place. Finally, 48 (79%) patients fulfilled the inclusion criteria and 31 (65%) were included in the study. There was no significant difference in the quality of life before and after cardiac arrest (EQ-5D-5L utility 0.79 vs. 0.78, p = 0.567) and in the EQ-5D-5L visual analogue scale (VAS) score. CONCLUSION: The quality of life before and after IHCA in survivors was good and comparable. The quality of life was mostly affected by reduced mobility and anxiety/depression. Future studies with larger patient samples should focus on potentially modifiable factors that could prevent, warn, and limit the consequences of in-hospital cardiac arrest. Moreover, research on outcomes of IHCA should include available tools for the quality of life assessment.

Association of anti-factor Xa-guided anticoagulation with hemorrhage during ECMO support: A systematic review and meta-analysis.

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.

Organ Donation from Patients Receiving Extracorporeal Membrane Oxygenation: A Systematic Review.

OBJECTIVE: The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors. DESIGN: Systematic literature review (Scopus and PubMed, up to October 11, 2023). SETTING: All study designs. PARTICIPANTS: Organ recipients from patients on ECMO at the time of death. INTERVENTION: Outcome of organ donation from ECMO donors. MEASUREMENTS AND MAIN RESULTS: The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years. CONCLUSION: Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage.

ECMO in Myocardial Infarction-Associated Cardiogenic Shock: Blood Biomarkers as Predictors of Mortality.

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.

Extracorporeal Life Support for Patients With Newly Diagnosed HIV and Acute Respiratory Distress Syndrome: A Systematic Review and Analysis of Individual Patient Data.

Extracorporeal membrane oxygenation (ECMO) may improve survival in patients with severe acute respiratory distress syndrome (ARDS). However, presence of immunosuppression is a relative contraindication for ECMO, which is withheld in HIV patients. We performed a systematic review to investigate the outcome of newly diagnosed HIV patients with ARDS receiving ECMO support. Our search yielded 288 publications, with 22 studies finally included. Initial presentation included fever, respiratory distress, and cough. Severe immunodeficiency was confirmed in most patients. Deceased patients had a higher viral load, a lower Horovitz index, and antiretroviral therapy utilized before ECMO. Moreover, ECMO duration was longer ( p = 0.0134), and all deceased suffered from sepsis ( p = 0.0191). Finally, despite the development of therapeutic options for HIV patients, ECMO remains a relative contraindication. We found that ECMO may successfully bridge the time for pulmonary recovery in 93% of patients, with a very good outcome. Using ECMO, the time for antimicrobial therapy, lung-protective ventilation, and immune system restitution may be gained. Further studies clarifying the role of ECMO in HIV are crucial and until these data are available, ECMO might be appropriate in immunocompromised patients. This holds especially true in newly diagnosed HIV patients, who are usually young, without comorbidities, with a good rehabilitation potential.

Cytomegalovirus Disease as a Risk Factor for Invasive Fungal Infections in Liver Transplant Recipients under Targeted Antiviral and Antimycotic Prophylaxis.

Cytomegalovirus (CMV) infection is the most common opportunistic infection that occurs following orthotopic liver transplantation (OLT). In addition to the direct infection-related symptoms, it also triggers an immunological response that may contribute to adverse clinical outcomes. CMV disease has been described as a predictor of invasive fungal infections (IFIs) but its role under an antiviral prophylaxis regimen is unclear. METHODS: We retrospectively analyzed the medical records of 214 adult liver transplant recipients (LTRs). Universal antiviral prophylaxis was utilized in recipients with CMV mismatch; intermediate- and low-risk patients received pre-emptive treatment. RESULTS: Six percent of patients developed CMV disease independent of their serostatus. The occurrence of CMV disease was associated with elevated virus load and increased incidence of leucopenia and IFIs. Furthermore, CMV disease was associated with higher one-year mortality and increased relapse rates within the first year of OLT. CONCLUSIONS: CMV disease causes significant morbidity and mortality in LTRs, directly affecting transplant outcomes. Due to the increased risk of IFIs, antifungal prophylaxis for CMV disease may be appropriate. Postoperative CMV monitoring should be considered after massive transfusion, even in low-risk serostatus constellations. In case of biliary complications, biliary CMV monitoring may be appropriate in the case of CMV-DNA blood-negative patients.

Invasive Fungal Infections: The Early Killer after Liver Transplantation.

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.

aPTT-guided anticoagulation monitoring during ECMO support: A systematic review and meta-analysis.

INTRODUCTION: The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed anticoagulation. Systemic anticoagulation bears an additional risk of serious bleeding, and its monitoring is of immense importance. Therefore, our work aims to analyze the association of anticoagulation monitoring with bleeding during ECMO support. MATERIAL AND METHODS: Systematic literature review and meta-analysis, complying with the PRISMA guidelines (PROSPERO-CRD42022359465). RESULTS: Seventeen studies comprising 3249 patients were included in the final analysis. Patients experiencing hemorrhage had a longer activated partial thromboplastin time (aPTT), a longer ECMO duration, and higher mortality. We could not find strong evidence of any aPTT threshold association with the bleeding occurrence, as less than half of authors reported a potential relationship. Finally, we identified the acute kidney injury (66%, 233/356) and hemorrhage (46%, 469/1046) to be the most frequent adverse events, while almost one-half of patients did not survive to discharge (47%, 1192/2490). CONCLUSION: The aPTT-guided anticoagulation is still the standard of care in ECMO patients. We did not find strong evidence supporting the aPTT-guided monitoring during ECMO. Based on the weight of the available evidence, further randomized trials are crucial to clarify the best monitoring strategy.

Association of aPTT-Guided Anticoagulation Monitoring with Thromboembolic Events in Patients Receiving V-A ECMO Support: A Systematic Review and Meta-Analysis.

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.

Invasive Fungal Infections after Liver Transplantation.

Invasive fungal infections represent a major challenge in patients who underwent organ transplantation. Overall, the most common fungal infections in these patients are candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Several risk factors have been identified, which increase the likelihood of an invasive fungal infection developing after transplantation. Liver transplant recipients constitute a high-risk category for invasive candidiasis and aspergillosis, and therefore targeted prophylaxis is favored in this patient population. Furthermore, a timely implemented therapy is crucial for achieving optimal outcomes in transplanted patients. In this article, we describe the epidemiology, risk factors, prophylaxis, and treatment strategies of the most common fungal infections in organ transplantation, with a focus on liver transplantation.

Hemorrhagic Shock: Blood Marker Sequencing and Pulmonary Gas Exchange.

BACKGROUND: The early identification of internal hemorrhage in critically ill patients may be difficult. Besides circulatory parameters, hemoglobin and lactate concentration, metabolic acidosis and hyperglycemia serve as laboratory markers for bleeding. In this experiment, we examined pulmonary gas exchange in a porcine model of hemorrhagic shock. Moreover, we sought to investigate if a chronological order of appearance regarding hemoglobin, lactatemia, standard base excess/deficit (SBED) and hyperglycemia exists in early severe hemorrhage. METHODS: In this prospective, laboratory study, twelve anesthetized pigs were randomly allocated to exsanguination or a control group. Animals in the exsanguination group (n = 6) endured a 65% blood loss over 20 min. No intravenous fluids were administered. Measurements were taken before, immediately after, and at 60 min after the completed exsanguination. Measurements included pulmonary and systemic hemodynamic variables, hemoglobin concentration, lactate, base excess (SBED), glucose concentration, arterial blood gases, and a multiple inert gas assessment of pulmonary function. RESULTS: At baseline, variables were comparable. Immediately after exsanguination, lactate and blood glucose were increased (p = 0.001). The arterial partial pressure of oxygen was increased at 60 min after exsanguination (p = 0.04) owing to a decrease in intrapulmonary right-to-left shunt and less ventilation-perfusion inequality. SBED was different to the control only at 60 min post bleeding (p < 0.001). Hemoglobin concentration did not change at any time (p = 0.97 and p = 0.14). CONCLUSIONS: In experimental shock, markers of blood loss became positive in chronological order: lactate and blood glucose concentrations were raised immediately after blood loss, while changes in SBED lagged behind and became significant one hour later. Pulmonary gas exchange is improved in shock.

Thrombotic Events Develop in 1 Out of 5 Patients Receiving ECMO Support: An 11-Year Referral Centre Experience.

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.

Incidence of Invasive Fungal Infections in Liver Transplant Recipients under Targeted Echinocandin Prophylaxis.

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.

Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients.

Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.

ECMO in Cardiogenic Shock: Time Course of Blood Biomarkers and Associated Mortality.

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.

ECMO Support in Refractory Cardiogenic Shock: Risk Factors for Mortality.

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.

Extracorporeal membrane oxygenation for cardiogenic shock: a meta-analysis of mortality and complications.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (va-ECMO) is an advanced life support for critically ill patients with refractory cardiogenic shock. This temporary support bridges time for recovery, permanent assist, or transplantation in patients with high risk of mortality. However, the benefit of this modality is still subject of discussion and despite the continuous development of critical care medicine, severe cardiogenic shock remains associated with high mortality. Therefore, this work aims to analyze the current literature regarding in-hospital mortality and complication rates of va-ECMO in patients with cardiogenic shock. METHODS: We conducted a systematic review and meta-analysis of the most recent literature to analyze the outcomes of va-ECMO support. Using the PRISMA guidelines, Medline (PubMed) and Scopus (Elsevier) databases were systematically searched up to May 2022. Meta-analytic pooled estimation of publications variables was performed using a weighted random effects model for study size. RESULTS: Thirty-two studies comprising 12756 patients were included in the final analysis. Between 1994 and 2019, 62% (pooled estimate, 8493/12756) of patients died in the hospital. More than one-third of patients died during ECMO support. The most frequent complications were renal failure (51%, 693/1351) with the need for renal replacement therapy (44%, 4879/11186) and bleeding (49%, 1971/4523), bearing the potential for permanent injury or death. Univariate meta-regression analyses identified age over 60 years, shorter ECMO duration and presence of infection as variables associated with in-hospital mortality, while the studies reporting a higher incidence of cannulation site bleeding were unexpectedly associated with a reduced in-hospital mortality. CONCLUSIONS: Extracorporeal membrane oxygenation is an invasive life support with a high risk of complications. We identified a pooled in-hospital mortality of 62% with patient age, infection and ECMO support duration being associated with a higher mortality. Protocols and techniques must be developed to reduce the rate of adverse events. Finally, randomized trials are necessary to demonstrate the effectiveness of va-ECMO in cardiogenic shock.

Early detection of COVID-19 cholangiopathy using cholangioscopy-a case report of two critically ill patients.

Background: The coronavirus disease 2019 (COVID-19) crisis caused by the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) rapidly led to a pandemic. While the majority of SARS-CoV-2-infected patients present with fever and respiratory symptoms, gastrointestinal symptoms may also occur. In addition, serious hepatic manifestations like cholangiopathy and liver failure have been described. Patients and methods: We identified two critically ill patients suffering from SARS-CoV­2 infection in our intensive care unit (ICU). In both patients, laboratory testing revealed elevated liver chemistries weeks after initial diagnosis with COVID-19. Results: During repeated endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy, a severely destructed biliary mucosa with ischemia and epithelial roughness was seen in both patients. Due to the prolonged course of COVID-19 and chronic liver damage with ongoing sepsis, both patients succumbed to the disease. Conclusion: In our opinion, a COVID-19 infection can lead to development of cholangiopathy in critically ill patients. Cholangioscopy performed early can confirm the diagnosis of COVID-19-associated cholangioscopy.

Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review.

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.