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Thromboelastometry point-of-care coagulation testing facilitates optimised management of bleeding. Previous thromboelastometry systems required the blood sample and liquid reagents to be pipetted in several manual steps by trained personnel. The ROTEMsigma coagulation analyser is a fully automated point-of-care device. We aimed to assess the reference ranges of the new device and to compare the results with those of the predecessor device, the ROTEMdelta. We took blood from healthy volunteers and from hyper- or hypocoagulable patients; blood samples from healthy volunteers served to determine reference ranges for the most important parameters for the ROTEMsigma: CTEXTEM 48-61 s; A5EXTEM 30-51 mm; MCFEXTEM 54-70 mm; CTINTEM 138-174 s; MCFINTEM 51-67 mm and MCFFIBTEM 5-24 mm. We then used blood samples from patients to compare the results obtained between the old and the new device. We found a strong correlation between the same tests performed on two ROTEMsigma devices and between the ROTEMsigma and the ROTEMdelta with respect to the determination of thromboelastometry parameters of hyper- and hypocoagulable patients (all p < 0.001 and R > 0.8). Performance evaluation for the ROTEMsigma device showed very high precision (R > 0.99, p < 0.001). Our reference ranges can serve as an important aid for other hospitals using this new device. [ABSTRACT FROM AUTHOR]

Abstract Background Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. Methods Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology. Results Arterial pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 105) CFU/ml for NaCl treated pigs (p = 0.4159). Conclusions Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.

Abstract Background N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model. Methods Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH4Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. Results Arterial pressure of oxygen (PaO2) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2) (p = 0.004). Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH4Cl (p = 0.05). Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25–0.5 mM). Conclusion The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.

Objective: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to reduce the risk of thromboembolic events. Despite its historic role, activated clotting time (ACT) remains a widely used heparin monitoring method. Systematic evidence on the association of ACT-guided monitoring with hemorrhagic or thromboembolic complications does not exist., Design: Systematic literature review and meta-analysis (Scopus and PubMed, July 2023)., Setting: All cohort studies., Participants: Patients receiving ECMO support., Intervention: Anticoagulation monitoring with ACT., Measurements and Main Results: We identified 3,177 publications, with 8 studies reporting the average ACT values for patients with and without bleeding. Meta-analysis revealed no significant difference in the compared groups (SMD = 0.69; 95% CI -0.05 to 1.43, p = 0.069; I 2  = 87.4%). Three studies (n = 117 patients) reported on the average ACT values for patients with thrombosis, without significant differences in ACT between patients with and without thrombosis (SMD = 0.47; 95% CI -0.50 to 1.44, p = 0.342; I 2  = 81.1%)., Conclusions: Even though ACT is a widely used heparin monitoring tool, the evidence on its association with hemorrhagic or thromboembolic events is still controversial and limited. Further studies are essential to elucidate the role of ACT in anticoagulation monitoring during ECMO support., Competing Interests: Declaration of competing interest All authors have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Extracorporeal cardiopulmonary resuscitation (eCPR) offers cardiorespiratory support to patients experiencing cardiac arrest. However, this technology is not yet considered a standard treatment, and the evidence on eCPR criteria and its association with survival and good neurological outcomes remains scarce. Therefore, we aimed to investigate the overall mortality and risk factors for mortality. Moreover, we provide a comparison of demographic, clinical, and laboratory characteristics of patients, including neurological outcomes and adverse events during support., Methods: This retrospective analysis included in-hospital and out-of-hospital cardiac arrest patients who received eCPR and were admitted between January 2008 and June 2022 at a tertiary and trauma one-level university hospital in Austria., Results: In total, 90 patients fulfilled inclusion criteria, 41 (46%) patients survived until intensive care unit discharge, and 39 (43%) survived until hospital discharge. The most common cause of cardiac arrest was myocardial infarction (42, 47%), and non-shockable initial rhythm was reported in 50 patients (56%). Of 33 survivors with documented outcomes, 30 had a good recovery as measured with Cerebral Performance Category score, 2 suffered severe disability, and 1 remained in a persistent vegetative state. Finally, multivariate analysis identified asystole as initial rhythm (HR 2.88, p = 0.049), prolonged CPR (HR 1.02, p = 0.043), and CPR on the weekend (HR 2.57, p = 0.032) as factors with a higher risk of mortality., Conclusions: eCPR-related decision-making could be additionally supported by the comprehension of the reported risk factors for mortality and severe disability. Further studies are needed to elucidate the impact of peri-arrest variables on outcomes, aiming to improve patient selection.

Objective: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to maintain the circuit patency. However, the use of anticoagulation carries a risk of severe hemorrhage, necessitating rigorous monitoring. Activated clotting time (ACT) is a widely used monitoring tool; however, the evidence of its correlation with unfractionated heparin (UFH) infusion dose is limited. Here we aimed to analyze the correlation between ACT and UFH infusion during ECMO., Design: Systematic literature review and meta-analysis of correlation coefficients (Scopus and PubMed, up to July 13, 2024)., Prospero: CRD42023448888 SETTING: All retrospective and prospective studies PARTICIPANTS: Patients receiving ECMO support INTERVENTION: Anticoagulation monitoring during ECMO support MEASUREMENTS AND MAIN RESULTS: Nineteen studies were included in the analysis, and the meta-analysis encompassed 16 studies. The vast majority of studies (n = 15) found a weak correlation, and no study reported a strong correlation between ACT and UFH infusion dose. The meta-analysis (n = 12,625 samples) identified a weak correlation, with a pooled estimate of correlation coefficients of 0.132 (95% confidence interval 0.03-0.23). The most common adverse events were hemorrhage (pooled incidence, 45%) and thrombosis (30%), and 47% of the patients died during their hospital stay., Conclusions: Even though ACT is a widely used UFH monitoring tool in ECMO patients, our meta-analysis found a weak correlation between ACT and UFH infusion dose. New trials are needed to investigate the role of emerging tools and to clarify the most appropriate monitoring strategy for patients receiving ECMO support., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The global shortage of solid organs for transplantation is exacerbated by high demand, resulting in organ deficits and steadily growing waiting lists. Diverse strategies have been established to address this issue and enhance organ availability, including the use of organs from individuals who have undergone extracorporeal cardiopulmonary resuscitation (eCPR). The main aim of this work was to examine the outcomes for both graft and recipients of solid organ transplantations sourced from donors who underwent eCPR., Methods: We performed a systematic literature review using a combination of the terms related to extracorporeal life support and organ donation. Using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, PubMed and Scopus databases were searched up to February 2024., Results: From 1764 considered publications, 13 studies comprising 130 donors and 322 organ donations were finally analyzed. On average, included patients were 36 y old, and the extracorporeal life support was used for 4 d. Kidneys were the most often transplanted organs (68%; 220/322), followed by liver (22%; 72/322) and heart (5%; 15/322); with a very good short-term graft survival rate (95% for kidneys, 92% for lungs, 88% for liver, and 73% for heart). Four studies with 230 grafts reported functional outcomes at the 1-y follow-up, with graft losses reported for 4 hearts (36%), 8 livers (17%), and 7 kidneys (4%)., Conclusions: Following eCPR, organs can be successfully used with very high graft and recipient survival. In terms of meeting demand, the use of organs from patients after eCPR might be a suitable method for expanding the organ donation pool., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

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 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., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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., (© 2022. The Author(s).)

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.

During the last five decades, lung sonography has developed into a core competency of intensive care medicine. It is a highly accurate bedside tool, with clear diagnostic criteria for most causes of respiratory failure (pneumothorax, pulmonary edema, pneumonia, pulmonary embolism, chronic obstructive pulmonary disease, asthma, and pleural effusion). It helps in distinguishing a hypovolemic from a cardiogenic, obstructive, or distributive shock. In addition to diagnostics, it can also be used to guide ventilator settings, fluid administration, and even antimicrobial therapy, as well as to assess diaphragmatic function. Moreover, it provides risk-reducing guidance during invasive procedures, e.g., intubation, thoracocentesis, or percutaneous dilatational tracheostomy. The recent pandemic has further increased its scope of clinical applications in the management of COVID-19 patients, from their initial presentation at the emergency department, during their hospitalization, and after their discharge into the community. Despite its increasing use, a consensus on education, assessment of competencies, and certification is still missing. Deep learning and artificial intelligence are constantly developing in medical imaging, and contrast-enhanced ultrasound enables new diagnostic perspectives. This review summarizes the clinical aspects of lung sonography in intensive care medicine and provides an overview about current training modalities, diagnostic limitations, and future developments.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in carefully selected patients with cardiac or respiratory failure. However, complications are common and can be associated with worse outcomes, while data on risk factors and outcomes are inconsistent and sparse. Therefore, we sought to investigate potential risk factors and predictors of haemorrhage and adverse events during ECMO and its influence on mortality. We retrospectively reviewed all patients on ECMO support admitted to intensive care units of a tertiary university centre in Austria. In a period of ten years, ECMO support was used in 613 patients, with 321 patients meeting the inclusion criteria of this study. Haemorrhage, occurring in more than one third of the included patients (123, 38%), represented the most common and serious ECMO complication, being associated with an increased one year mortality (51% vs. 35%, p = 0.005). The main risk factors for haemorrhage were severity of the disease (hazard ratio (HR) = 1.01, p = 0.047), a prolonged activated partial thromboplastin time (HR = 1.01, p = 0.007), and lower values of C-reactive protein (HR = 0.96, p = 0.005) and procalcitonin (HR = 0.99, p = 0.029). In summary, haemorrhage remained the main ECMO complication with increased mortality. Moreover, we reported a possible association of lower inflammation and bleeding during ECMO support for the first time. This generated a new hypothesis that warrants further research. Finally, we recommend stricter monitoring of anticoagulation especially in patients without hyperinflammation.

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.

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-CoV‑2 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., Competing Interests: Conflict of interestV. Kroepfl, B. Treml, M.C. Freund, and C. Profanter declare that they have no competing interests., (© The Author(s) 2022.)

The concept of intensive care units (ICU) has existed for almost 70 years, with outstanding development progress in the last decades. Multidisciplinary care of critically ill patients has become an integral part of every modern health care system, ensuing improved care and reduced mortality. Early recognition of severe medical and surgical illnesses, advanced prehospital care and organized immediate care in trauma centres led to a rise of ICU patients. Due to the underlying disease and its need for complex mechanical support for monitoring and treatment, it is often necessary to facilitate bed-side diagnostics. Immediate diagnostics are essential for a successful treatment of life threatening conditions, early recognition of complications and good quality of care. Management of ICU patients is incomprehensible without continuous and sophisticated monitoring, bedside ultrasonography, diverse radiologic diagnostics, blood gas analysis, coagulation and blood management, laboratory and other point-of-care (POC) diagnostic modalities. Moreover, in the time of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, particular attention is given to the POC diagnostic techniques due to additional concerns related to the risk of infection transmission, patient and healthcare workers safety and potential adverse events due to patient relocation. This review summarizes the most actual information on possible diagnostic modalities in critical care, with a special focus on the importance of point-of-care approach in the laboratory monitoring and imaging procedures.

Tigecycline is a novel glycylcycline broad-spectrum antibiotic offering good coverage for critically ill patients experiencing complicated infections. A known side effect is a coagulation disorder with distinct hypofibrinogenemia. To date, the information on possible risk factors and outcomes is sparse. Therefore, the aim of this study is to examine the time course of fibrinogen level changes during tigecycline therapy in critically ill patients. Moreover, we sought to identify risk factors for coagulopathy and to report on clinically important outcomes. We retrospectively reviewed all intensive care patients admitted to our General and Surgical Intensive Care Unit receiving tigecycline between 2010 and 2018. A total of 130 patients were stratified into two groups based on the extent of fibrinogen decrease. Patients with a greater fibrinogen decrease received a higher dose, a longer treatment and more dose changes of tigecycline, respectively. In regard to the underlying pathology, these patients showed higher inflammation markers as well as a slightly reduced liver synthesis capacity. We, therefore, conclude that such a fibrinogen decrease may be based upon further impairment of liver synthesis during severe inflammatory states. To decrease the risk of bleeding, cautious monitoring of coagulation in critically ill patients treated with high-dose tigecycline is warranted.

Pleural effusions are a common finding in critically ill patients and small bore chest drains (SBCD) are proven to be efficient for pleural drainage. The data on the potential benefits and risks of drainage remains controversial. We aimed to determine the cut-off volume for complications, to investigate the impact of pleural drainage and drained volume on clinically relevant outcomes. Medical records of all critically ill patients undergoing insertion of SBCD were retrospectively examined. We screened 13,003 chest radiographs and included 396 SBCD cases in the final analysis. SBCD drained on average 900 mL, with less amount in patients with complications ( p = 0.003). A drainage volume of 975 mL in 24 h represented the optimal threshold for complications. Pneumothorax was the most frequent complication (4.5%), followed by bleeding (0.8%). Female and lighter-weighted patients experienced a higher risk for any complication. We observed an improvement in the arterial partial pressure of oxygen and respiratory quotient ( p < 0.001). We conclude that the small drainage volumes are associated with complications in critically ill patients-the more you drain, the safer the procedure gets. The use of SBCD is a safe and efficient procedure, further investigations regarding the higher rate of complications in female and lighter-weighted patients are desirable.

Background: Scores can assess the severity and course of disease and predict outcome in an objective manner. This information is needed for proper risk assessment and stratification. Furthermore, scoring systems support optimal patient care, resource management and are gaining in importance in terms of artificial intelligence., Objective: This study evaluated and compared the prognostic ability of various common pediatric scoring systems (PRISM, PRISM III, PRISM IV, PIM, PIM2, PIM3, PELOD, PELOD 2) in order to determine which is the most applicable score for pediatric sepsis patients in terms of timing of disease survey and insensitivity to missing data., Methods: We retrospectively examined data from 398 patients under 18 years of age, who were diagnosed with sepsis. Scores were assessed at ICU admission and re-evaluated on the day of peak C-reactive protein. The scores were compared for their ability to predict mortality in this specific patient population and for their impairment due to missing data., Results: PIM (AUC 0.76 (0.68-0.76)), PIM2 (AUC 0.78 (0.72-0.78)) and PIM3 (AUC 0.76 (0.68-0.76)) scores together with PRSIM III (AUC 0.75 (0.68-0.75)) and PELOD 2 (AUC 0.75 (0.66-0.75)) are the most suitable scores for determining patient prognosis at ICU admission. Once sepsis is pronounced, PELOD 2 (AUC 0.84 (0.77-0.91)) and PRISM IV (AUC 0.8 (0.72-0.88)) become significantly better in their performance and count among the best prognostic scores for use at this time together with PRISM III (AUC 0.81 (0.73-0.89)). PELOD 2 is good for monitoring and, like the PIM scores, is also largely insensitive to missing values., Conclusion: Overall, PIM scores show comparatively good performance, are stable as far as timing of the disease survey is concerned, and they are also relatively stable in terms of missing parameters. PELOD 2 is best suitable for monitoring clinical course., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Mirjam Bachler has received personal fees and travel grants from LFB Biomedicaments, Takeda GmbH, CSL Behring GmbH, Mitsubishi Tanabe and non-financial support from TEM International outside the submitted work., (©2020 Niederwanger et al.)

Background: Testing the hypoxic ventilatory response (HVR) at low-altitude helps to detect those who do not hyperventilate appropriately in hypoxia but might not necessarily predict the HVR and the risk to develop acute mountain sickness (AMS) at high altitude. However, a low HVR seems to be particularly prevalent in individuals susceptible to high-altitude pulmonary edema (HAPE+). In this short communication, we assessed differences in physiological parameters in two comparable women before and 3 hours after exposure to 3,480 meters. One woman had a (clinically diagnosed) history of high-altitude pulmonary edema (HAPE+) while the other did well at previous exposures to high altitude (HAPE-)., Methods: Heart rate, blood pressure, ventilation, arterial blood gas variables, arterial haemoglobin saturation, haemoglobin concentration, arterial oxygen content and delta plasma volume were measured or calculated before and after arrival at high altitude., Results: At high altitude, plasma volume decreased in the HAPE- woman which in turn increased haemoglobin concentration. Ventilation was elevated in the HAPE- but not in the HAPE + woman. Arterial oxygen content fell in the HAPE + while it was preserved in the HAPE- woman. This resulted from lower peripheral oxygen saturation (-35%), lower haemoglobin concentration (-12%) and lower arterial partial pressure of oxygen (-59%) in the HAPE+., Conclusion: Considerable haemoglobin desaturation and lack of haemoconcentration were characteristics of the HAPE + woman when exposed to high altitude, while the higher arterial oxygen content in the HAPE- woman was related to both haemoconcentration and hyperventilation (and associated haemoglobin saturation)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Developing hypernatremia while on intensive care unit (ICU) is a common problem with various undesirable effects. A link to persistent inflammation, immunosuppression and catabolism syndrome (PICS) can be established in two ways. On the one hand, hypernatremia can lead to inflammation and catabolism via hyperosmolar cell stress, and on the other, profound catabolism can lead to hypernatremia via urea-induced osmotic diuresis. In this retrospective single-center study, we examined 115 patients with prolonged ICU stays (≥14 days) and sufficient renal function. Depending on their serum sodium concentrations between ICU day 7 and 21, allocation to a hypernatremic (high) and a nonhypernatremic group (low) took place. Distinct signs of PICS were detectable within the complete cohort. Thirty-three of them (28.7%) suffered from ICU-acquired hypernatremia, which was associated with explicitly higher signs of inflammation and ongoing catabolism as well as a prolonged ICU length of stay. Catabolism was discriminated better by the urea generation rate and the urea-to-creatinine ratio than by serum albumin concentration. An assignable cause for hypernatremia was the urea-induced osmotic diuresis. When dealing with ICU patients requiring prolonged treatment, hypernatremia should at least trigger thoughts on PICS as a contributing factor. In this regard, the urea-to-creatinine ratio is an easily accessible biomarker for catabolism.

The literature suggests that acute hypobaric (HH) and normobaric (NH) hypoxia exposure elicits different physiological responses. Only limited information is available on whether maximal cardiorespiratory exercise test outcomes, performed on either the treadmill or the cycle ergometer, are affected differently by NH and HH. A focused literature review was performed to identify relevant studies reporting cardiorespiratory responses in well-trained male athletes (individuals with a maximal oxygen uptake, VO 2 max > 50 mL/min/kg at sea level) to cycling or treadmill running in simulated acute HH or NH. Twenty-one studies were selected. The exercise tests in these studies were performed in HH ( n = 90) or NH ( n = 151) conditions, on a bicycle ergometer ( n = 178) or on a treadmill ( n = 63). Altitudes (simulated and terrestrial) varied between 2182 and 5400 m. Analyses (based on weighted group means) revealed that the decline in VO 2max per 1000 m gain in altitude was more pronounced in acute NH vs. HH (-7.0 ± 1.4% vs. -5.6 ± 0.9%). Maximal minute ventilation (VE max ) increased in acute HH but decreased in NH with increasing simulated altitude (+1.9 ± 0.9% vs. -1.4 ± 1.8% per 1000 m gain in altitude). Treadmill running in HH caused larger decreases in arterial oxygen saturation and heart rate than ergometer cycling in acute HH, which was not the case in NH. These results indicate distinct differences between maximal cardiorespiratory responses to cycling and treadmill running in acute NH or HH. Such differences should be considered when interpreting exercise test results and/or monitoring athletic training.

Red Bull energy drink is popular among athletes, students and drivers for stimulating effects or enhancing physical performance. In previous work, Red Bull has been shown to exert manifold cardiovascular effects at rest and during exercise. Red Bull with caffeine as the main ingredient increases blood pressure in resting individuals, probably due to an increased release of (nor)-epinephrine. Red Bull has been shown to alter heart rate or leaving it unchanged. Little is known about possible effects of caffeinated energy drinks on pulmonary ventilation/perfusion distribution at sea level or at altitude. Here, we hypothesized a possible alteration of pulmonary blood flow in ambient air and in hypoxia after Red Bull consumption. We subjected eight anesthetized piglets in normoxia (FiO 2 = 0.21) and in hypoxia (FiO 2 = 0.13), respectively, to 10 mL/kg Red Bull ingestion. Another eight animals served as controls receiving an equivalent amount of saline. In addition to cardiovascular data, ventilation/perfusion distribution of the lung was assessed by using the multiple inert gas elimination technique (MIGET). Heart rate increased in normoxic conditions but was not different from controls in acute short-term hypoxia after oral Red Bull ingestion in piglets. For the first time, we demonstrate an increased fraction of pulmonary shunt with unchanged distribution of pulmonary blood flow after Red Bull administration in acute short-term hypoxia. In summary, these findings do not oppose moderate consumption of caffeinated energy drinks even at altitude at rest and during exercise.

Intermittent normobaric hypoxia (IH) is increasingly used to pre-acclimatize for a sojourn to high altitude. There is a number of hypoxia - protocols observing the hypoxic ventilatory response (HVR), but little is known about the carry - over quality of the Lake Louise Score (LLS). We thus studied a week - long, 1 h per day poikilocapnic hypoxia protocol on whether acclimatization could be carried over for one week. Rationale for this was that it usually takes one week to get from Europe, Britain or the United States to the base camp of a major mountain. Forty-nine healthy volunteers of both sexes were exposed to daily bouts of 1 h at an inspiratory fraction of oxygen (FiO 2 ) of 0.11 or 0.21 (control) for 7 consecutive days. Seven days after cessation of IH or sham exposures participants were again subjected to hypoxia (FiO 2 = 0.11) for 6 h and measurements of isocapnic HVR and blood gases out of the arterialized earlobe were taken and LLS was assessed. In those with IH exposures LLS was reduced which was not the case in those with sham exposure (87 vs. 50%). Changes in HVR or the arterial hemoglobin saturation were not observed. Gender neither affected LLS nor HVR nor blood gases or carry -over quality. We found that our week - long, hypoxia protocol grants a reduction in LLS that can be carried over the time span of one week. In this way, antedated acclimatization may improve safety and comfort on the mountain., (Copyright © 2020 Treml, Kleinsasser, Hell, Knotzer, Wille and Burtscher.)

The current study aims to evaluate whether prophylactic anticoagulation using argatroban or an increased dose of unfractionated heparin (UFH) is effective in achieving the targeted activated partial thromboplastin time (aPTT) of more than 45 s in critically ill heparin-resistant (HR) patients. Patients were randomized either to continue receiving an increased dose of UFH, or to be treated with argatroban. The endpoints were defined as achieving an aPTT target of more than 45 s at 7 h and 24 h. This clinical trial was registered on clinicaltrials.gov (NCT01734252) and on EudraCT (2012-000487-23). A total of 42 patients, 20 patients in the heparin and 22 in the argatroban group, were included. Of the patients with continued heparin treatment 55% achieved the target aPTT at 7 h, while only 40% of this group maintained the target aPTT after 24 h. Of the argatroban group 59% reached the target aPTT at 7 h, while at 24 h 86% of these patients maintained the targeted aPTT. Treatment success at 7 h did not differ between the groups ( p = 0.1000), whereas at 24 h argatroban showed significantly greater efficacy ( p = 0.0021) than did heparin. Argatroban also worked better in maintaining adequate anticoagulation in the further course of the study. There was no significant difference in the occurrence of bleeding or thromboembolic complications between the treatment groups. In the case of heparin-resistant critically ill patients, argatroban showed greater efficacy than did an increased dose of heparin in achieving adequate anticoagulation at 24 h and in maintaining the targeted aPTT goal throughout the treatment phase., Competing Interests: Mirjam Bachler has received research funding and travel grants from LFB Biomedicaments, Baxter GmbH, CSL Behring GmbH, and Mitsubishi Tanabe, as well as non-financial support from TEM International outside the submitted work. Benedikt Treml has received travel grants from Pfizer. Bettina Schenk has received travel grants, and honoraria for speaking or participation at meetings from CSL Behring, BBraun, and Biotest. Dietmar Fries has received study funding, as well as honoraria for consultancy and board activity from Astra Zeneca, AOP orphan, Baxter, Baer, BBraun, Biotest, CSL Behring, Delta Select, Dae Behring, Edwards, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB, Mitsubishi Pharma, NovoNordisk, Octapharm, Pfizer, and Tem-Innovation outside the submitted work. The other authors (Tobias Hell, Johannes Bösch, Barbara Friesenecker, Benjamin Treichl, Ingo Lorenz, Daniel Stengg, Stefan Hruby, Bernd Wallner, Elgar Oswald, Mathias Ströhle, Christian Niederwanger, and Christian Irsara) declared no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Tigecycline offers broad anti-bacterial coverage for critically ill patients with complicated infections. A described but less researched side effect is coagulopathy. The aim of this study was to test whether tigecycline interferes with fibrinogen polymerization by peripheral interactions. To study the effect of unmetabolized tigecycline, plasma of healthy volunteers were spiked with increasing concentrations of tigecycline. In a second experimental leg, immortalized human liver cells (HepG2) were treated with the same concentrations to test an inhibitory effect of hepatic tigecycline metabolites. Using standard coagulation tests, only the activated thromboplastin time in humane plasma was prolonged with increasing concentrations of tigecycline. Visualization of the fibrin network using confocal live microscopy demonstrated a qualitative difference in tigecycline treated experiments. Thrombelastometry and standard coagulation tests did not indicate an impairment of coagulation. Although the discrepancy between functional and immunologic fibrinogen levels increased in cell culture assays with tigecycline concentration, fibrinogen levels in spiked plasma samples did not show significant differences determined by functional versus immunologic methods. In our in vitro study, we excluded a direct effect of tigecycline in increasing concentrations on blood coagulation in healthy adults. Furthermore, we demonstrated a rapid loss of mitochondrial activity in hepatic cells with supra-therapeutic tigecycline dosages., Competing Interests: The authors declare no conflict of interest.

FXII deficiency results in spontaneous prolongation of activated partial thromboplastin time (aPTT), which is widely used to monitor thromboprophylaxis. Misinterpretation of spontaneously prolonged aPTT may result in omission of thromboembolic treatment or even unnecessary transfusion of blood products. This retrospective analysis was performed to calculate a threshold level of FXII resulting in aPTT prolongation. 79 critically ill patients with spontaneous prolongation of aPTT were included. A correlation analysis and a ROC curve for aPTT prolongation predicted by FXII level were created to find the FXII threshold level. Prolongation of aPTT was associated with disease severity. A significant inverse proportionality between FXII and aPTT was seen. A ROC curve for aPTT prolongation, predicted by FXII level (AUC 0.85; CI 0.76-0.93), revealed a FXII threshold level of 42.5%. Of our patients 50.6% experienced a FXII deficiency, in 80.0% of whom we found aPTT to be prolonged without a significantly higher bleeding rate. The FXII deficiency was more common in patients with higher SAPS3 scores, septic shock, transfusion of red blood cells and platelet concentrates as well as in patients receiving renal replacement therapy. Patients with a FXII deficiency and prolonged aPTT less often received anticoagulatory therapy although they were more severely ill. The rate of thromboembolic events was higher in these patients although the difference was not statistically significant. Of all patients with spontaneous aPTT prolongation 50.6% had a FXII level of 42.5% or less. Those patients received insufficient thromboembolic prophylaxis.

Purpose of Review: Anticoagulants in general, but especially the relatively new direct oral anticoagulants and platelet inhibitors, pose a great challenge for physicians in the hemorrhaging patient. The aim of the present review is to provide an overview on recent studies dealing with the reversal of anticoagulation in the hemorrhaging patient and to describe our therapeutic emergency strategy for those patients., Recent Findings: A specific antidote for dabigatran is already on the market and antidotes for the direct and indirect factor Xa inhibitors are in development. Moreover, bleeding under platelet inhibitors remains critical with very little evidence on effective reversal strategies., Summary: To reverse anticoagulation in the hemorrhaging patient, specific antidotes should be the first option if available, followed by four-factor prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor seven as the emergency strategy. Fibrinogen concentrate, antifibrinolytics and oral charcoal, respectively, can be considered as an additional measure. Massive blood loss and thrombocytopenia should be treated independently according to the respective, local guidelines for (massive) transfusion of blood and blood products.

Thromboelastometry point-of-care coagulation testing facilitates optimised management of bleeding. Previous thromboelastometry systems required the blood sample and liquid reagents to be pipetted in several manual steps by trained personnel. The ROTEMsigma coagulation analyser is a fully automated point-of-care device. We aimed to assess the reference ranges of the new device and to compare the results with those of the predecessor device, the ROTEMdelta. We took blood from healthy volunteers and from hyper- or hypocoagulable patients; blood samples from healthy volunteers served to determine reference ranges for the most important parameters for the ROTEMsigma: CT EXTEM 48-61 s; A5 EXTEM 30-51 mm; MCF EXTEM 54-70 mm; CT INTEM 138-174 s; MCF INTEM 51-67 mm and MCF FIBTEM 5-24 mm. We then used blood samples from patients to compare the results obtained between the old and the new device. We found a strong correlation between the same tests performed on two ROTEMsigma devices and between the ROTEMsigma and the ROTEMdelta with respect to the determination of thromboelastometry parameters of hyper- and hypocoagulable patients (all p < 0.001 and R > 0.8). Performance evaluation for the ROTEMsigma device showed very high precision (R > 0.99, p < 0.001). Our reference ranges can serve as an important aid for other hospitals using this new device., (© 2018 Association of Anaesthetists.)