The ADVanced Organ Support (ADVOS) hemodialysis system removes IL-6: an in vitro proof-of-concept study.

BACKGROUND: IL-6 is a pleiotropic cytokine modulating inflammation and metabolic pathways. Its proinflammatory effect plays a significant role in organ failure pathogenesis, commonly elevated in systemic inflammatory conditions. Extracorporeal blood purification devices, such as the Advanced Organ Support (ADVOS) multi hemodialysis system, might offer potential in mitigating IL-6's detrimental effects, yet its efficacy remains unreported. METHODS: We conducted a proof-of-concept in vitro study to assess the ADVOS multi system's efficacy in eliminating IL-6. Varying concentrations of IL-6 were introduced into a swine blood model and treated with ADVOS multi for up to 12 h, employing different blood and concentrate flow rates. IL-6 reduction rate, clearance, and dynamics in blood and dialysate were analyzed. RESULTS: IL-6 clearance rates of 0.70 L/h and 0.42 L/h were observed in 4 and 12-h experiments, respectively. No significant differences were noted across different initial concentrations. Reduction rates ranged between 40 and 46% within the first 4 h, increasing up to 72% over 12 h, with minimal impact from flow rate variations. Our findings suggest that an IL-6-albumin interaction and convective filtration are implicated in in vitro IL-6 elimination with ADVOS multi. CONCLUSIONS: This study demonstrates for the first time an efficient and continuous in vitro removal of IL-6 by ADVOS multi at low blood flow rates. Initial concentration-dependent removal transitions to more consistent elimination over time. Further clinical investigations are imperative for comprehensive data acquisition.

Safety and efficacy of Single-Pass Albumin Dialysis (SPAD), Prometheus, and Molecular Adsorbent Recycling System (MARS) liver haemodialysis vs. Standard Medical Therapy (SMT): meta-analysis and systematic review.

Introduction: Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned.Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction. Material and methods: PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment. Results: Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; p < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; p = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; p = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; p = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; p = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; p = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; p = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; p = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; p = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; p = 0.31, respectively). Conclusions: MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events.

Toxin-Induced Liver Injury and Extracorporeal Treatment of Liver Failure.

Poisoning with a large variety of drugs and naturally occurring toxins may result in acute liver injury and failure. Drug-induced liver injury is a major cause of liver failure nationwide, and it is likely that nephrologists will be involved in treating patients with these conditions. A number of xenobiotics resulting in liver toxicity may cause acute kidney injury or other organ injury as well. Most agents causing drug- or toxin-induced liver failure lack specific therapies, although a few xenobiotics such as acetaminophen have effective antidotal therapies if administered prior to development of hepatotoxicity. The nephrologist should be aware that extracorporeal treatment of liver failure associated with drugs and toxins may be indicated, including therapies conventionally performed by nephrologists (hemodialysis, continuous kidney replacement therapy), therapies occasionally performed by nephrologists and other specialists (plasma exchange, albumin dialysis, hemadsorption), and therapies performed by other specialists (extracorporeal membrane oxygenation). An overview of the role of these therapies in liver failure is provided, as well as a review of their limitations and potential complications.

Nontraditional Treatment of Hepatic Encephalopathy.

The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.

The Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis.

INTRODUCTION: Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy. METHODS: We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization. RESULTS: We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small "positive" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes. CONCLUSIONS: This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.

Extracorporeal albumin dialysis in critically ill patients with liver failure: Comparison of four different devices-A retrospective analysis.

BACKGROUND: Besides standard medical therapy and critical care monitoring, extracorporeal liver support may provide a therapeutic option in patients with liver failure. However, little is known about detoxification capabilities, efficacy, and efficiency among different devices. METHODS: Retrospective single-center analysis of patients treated with extracorporeal albumin dialysis. Generalized Estimating Equations with robust variance estimator were used to account for repeated measurements of several cycles and devices per patient. RESULTS: Between 2015 and 2021 n = 341 cycles in n = 96 patients were eligible for evaluation, thereof n = 54 (15.8%) treatments with Molecular Adsorbent Recirculating System, n = 64 (18.7%) with OpenAlbumin, n = 167 (48.8%) Advanced Organ Support treatments, and n = 56 (16.4%) using Single Pass Albumin Dialysis. Albumin dialysis resulted in significant bilirubin reduction without differences between the devices. However, ammonia levels only declined significantly in ADVOS and OPAL. First ECAD cycle was associated with highest percentage reduction in serum bilirubin. With the exception of SPAD all devices were able to remove the water-soluble substances creatinine and urea and stabilized metabolic dysfunction by increasing pH and negative base excess values. Platelets and fibrinogen levels frequently declined during treatment. Periprocedural bleeding and transfusion of red blood cells were common findings in these patients. CONCLUSIONS: From this clinical perspective ADVOS and OPAL may provide higher reduction capabilities of liver solutes (i.e. bilirubin and ammonia) in comparison to MARS and SPAD. However, further prospective studies comparing the effectiveness of the devices to support liver impairment (i.e. bile acid clearance or albumin binding capacity) as well as markers of renal recovery are warranted.

Modeling and Validation of an Ultra-Compact Regenerative Liver Dialysis Device.

The availability of a wearable artificial liver that facilitates extracorporeal dialysis outside of medical facilities would represent a significant advancement for patients requiring dialysis. The objective of this preliminary investigation is to explore, using validated mathematical models based on in vitro data, the feasibility of developing a novel, cost-effective, and highly compact extracorporeal liver support device that can be employed as a transitional therapy to transplantation outside of clinical settings. Such an innovation would offer substantial cost savings to the national healthcare system while significantly improving the patient's quality of life. The experimental components consisted of replacing traditional adsorbent materials with albumin-functionalized silica microspheres due to their capacity to adsorb bilirubin, one of the toxins responsible for liver failure. Two configurations of the dialysis module were tested: one involved dispersing the adsorbent particles in dialysis fluid, while the other did not require dialysis fluid. The results demonstrate the superior performance of the first configuration compared to the second. Although the clinical applicability of these models remains distant from the current stage, further studies will focus on optimizing these models to develop a more compact and wearable device.

Liver support systems and liver transplantation in acute liver failure.

Acute liver failure (ALF) results in a multitude of complications that result in multi-organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia-producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non-paracetamol cases appear robust while the criteria for paracetamol-intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post-LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.

Efficacy of hemoperfusion with Seraph-100 in series with single pass albumin dialysis in acute hepatitis B infection: A case report.

Acute and acute-on-chronic liver failure is a cause of death in patients suffering from viral hepatitis, and many cases need liver transplantation. Infection from hepatitis B virus may range from asymptomatic to severe acute and fulminant hepatitis. In this setting, treatment is mainly supportive as there is no consensus on antiviral therapy based on non-nucleoside reverse transcriptase inhibitors. Single-pass albumin dialysis is a liver-support technique for patients suffering from liver failure, that has shown effectiveness in the removal of both water-soluble and albumin-bound toxins, which accumulate due to impairment of the liver's cleansing function. We report here the case of a 62-year-old male who presented with a severe acute hepatitis B infection, liver failure, and marked hyperbilirubinemia. Treatment with single-pass albumin dialysis combined with a hemoperfusion device was successful in improving clinical, physiological, and laboratory parameters.

Successful use of single-pass albumin dialysis in the correction of severe hyperbilirubinemia in a case of acute hepatitis E.

INTRODUCTION: Acute liver failure (ALF) is a rare syndrome defined by the rapid loss of liver function in the absence of pre-existing liver disease, which may be secondary to hepatitis A virus, hepatitis E virus (HEV), or to drugs in about 50% of cases. Extracorporeal albumin dialysis enables the elimination of albumin-bound toxins that accumulate in liver failure. METHODS: We report a case of ALF secondary to HEV associated with severe hyperbilirubinemia. Patient was treated with four consecutive sessions of single-pass albumin dialysis (SPAD) carried out setting the following parameters: time: 300 min, Qb: 60 mL/min, Qd: 800-1000 mL/min, dialysate containing 4% albumin, citrate: 3-4 mmol/L. RESULT: SPAD documented good support of liver function. Bilirubin levels were reduced from 22 to 14 g/dL after four treatments. Pruritus was the first clinical sign of improvement. CONCLUSION: SPAD system can represent a safe and effective therapeutic option.

Extracorporeal Liver Support: An Updated Review of Mechanisms and Current Literature.

Introduction: Acute liver failure is a cause of major mortality in the United States. Although the liver possesses regenerative capabilities, liver transplantation is the mainstay of treating acute liver failure. This modality is associated with many financial and logistic challenges. In this regard, Extracorporeal Liver Support (ECLS) might help in reducing mortality as well as bridge a patient to liver transplant. In some cases, the sequelae of liver failure such as hepatic encephalopathy and multi-organ failure can be postponed long enough for the native liver to self-recover function. With this rationale, we sought to describe the mechanism of various ECLS modalities, provide an overview of the current evidence regarding its use and to highlight future advancements that could overcome hindrances in its use. Methods: A scoping review was performed using PubMed and other databases from 1990 to 2020 with the keywords: 'extracorporeal liver support', 'acute liver failure', 'acute on chronic liver failure', 'albumin dialysis', 'artificial' and 'bioartificial'. Results and conclusions: ECLS has shown significant improvements in bilirubin and urea levels. Various forms of ECLS might also reduce mortality due to liver failure. However, many complications, such as hypotension, anemia, bleeding issues, sepsis, can be anticipated. There are a few barriers to mainstream use of ECLS, such as specific design requirements and high cost that reduce the overall utility of this modality in a small group of liver transplant candidates. Furthermore, a multidisciplinary team approach is required to supervise ECLS, a luxury only available at major academic hospitals. Some advancements for overcoming these barriers include investigation of new scaffolding systems. In order to expand the usage of ECLS, clinical trials focusing on a comparison of different modalities of ECLS with renal replacement therapy in patients with liver failure should be promoted.

Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts.

The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert's recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts' statements may help careful patient selection and better treatment modalities.

Use of extracorporeal membrane oxygenation in massive amlodipine overdose.

Calcium-channel blocker overdose can result in profound vasoplegia and cardiogenic shock, which can quickly spiral into multi-organ failure and death. In this case report, we discuss two separate cases of massive amlodipine overdose with polydrug intoxication (Patient A: amlodipine and quetiapine; Patient B: amlodipine, fluoxetine and zopiclone), both of which were complicated by life-threatening vasoplegic shock refractory to supportive therapy (endotracheal intubation, fluid resuscitation, activated charcoal, vasopressors and inotropes), multimodal antidotes (calcium and hyper-insulinemic euglycemic therapy) and even second-line treatment (methylene blue and therapeutic plasma exchange). Despite exhausting all therapeutic options, resuscitation remained futile with no clinical response elicited until veno-arterial extracorporeal membrane oxygenation (ECMO) salvage therapy was initiated in both cases as a bridge-to-recovery. Albumin dialysis was also commenced to further enhance elimination of amlodipine given its high plasma protein-binding properties. Both patients improved drastically once perfusion to vital organs was maintained by ECMO and eventually survived with good neurological outcomes and preserved cardiac contractility on discharge. This case report supports the growing evidence that although ECMO support represents a potentially life-saving salvage therapy for refractory poisoning-induced shock, escalation to ECMO must be considered and instituted early before irreversible multi-organ failure sets in to ensure good clinical outcomes.

The Efficacy of Albumin Dialysis in the Treatment of Severe Cholestatic Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a significant cause of acute liver injury and can present as cholestatic injury with or without associated hepatitis. Although most patients with DILI recover with supportive care, some can develop severe refractory cholestasis that impairs recovery of hepatic function, with subsequent progression to acute or chronic liver failure. Current pharmacotherapy and extracorporeal therapies such as hemodialysis have limited benefit. Albumin dialysis is an emerging strategy in the extracorporeal treatment of intoxications caused by protein bound drugs and can be used for the removal of albumin bound bilirubin and bile acids. CASES SERIES: We describe the efficacy of albumin dialysis with the molecular adsorbent recirculating system (MARS) in the successful treatment of five patients with severe cholestatic DILI that was refractory to standard medical therapy. All patients had a sustained improvement in serum bilirubin levels after completing MARS therapy, with a complete resolution of their liver injury. DISCUSSION: Our case series demonstrates that albumin dialysis could provide an important treatment strategy in the setting of severe refractory cholestatic DILI and be considered as a novel therapeutic option in specific cases of drug hepatotoxicity in which the causative agent has high protein binding characteristics.

Influence of Advanced Organ Support (ADVOS) on Cytokine Levels in Patients with Acute-on-Chronic Liver Failure (ACLF).

Background: ADVanced Organ Support (ADVOS) is a novel type of extracorporeal albumin dialysis that supports multiorgan function in patients with acute-on-chronic liver failure (ACLF). No data exist on whether ADVOS affects inflammatory cytokine levels, which play a relevant role in ACLF. Aim: Our aim was to quantify cytokine levels both before and after a single ADVOS treatment in patients with ACLF at a regular dialysis ward. Methods and results: In this prospective study, 15 patients (60% men) with ACLF and an indication for renal replacement therapy were included. Patient liver function was severely compromised, reflected by a median CLIF-consortium ACLF score of 38 (IQR 35; 40). Blood samples were directly taken before and after ADVOS dialysis. The concentration of cytokines for IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33 were quantified via a cytometric bead array. We found no significant (p > 0.05) change in cytokine levels, even when patients were stratified for dialysis time (<480 min versus ≥480 min). The relevance of the assessed cytokines in contributing to systemic inflammation in ACLF was demonstrated by Ingenuity pathway analysis®. Conclusion: Concentrations of pathomechanistically relevant cytokines remained unchanged both before and after ADVOS treatment in patients with ACLF.

The role of the ADVanced Organ Support (ADVOS) system in critically ill patients with multiple organ failure.

BACKGROUND: Multi-organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification. METHODS: We performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system. RESULTS: In porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water-soluble and protein-bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2 ) effectively with rapid correction of pH abnormalities, achieving normalization of CO2 , and bicarbonate levels. In patients with COVID-19 infection, ADVOS enables rapid correction of acid-base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi-organ failure and has been shown to be safe with minimal adverse events. CONCLUSIONS: From the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water-soluble and protein-bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid-based direct removal of acid and CO2 . ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi-organ failure, and is well-tolerated. Larger randomized trials are now necessary to further validate these encouraging results.

Single-pass albumin dialysis and hemoadsorption for bilirubin and bile acids removal for a child with hyperbilirubinemia after ventricular assist device implantation.

We report the successful management of hyperbilirubinemia using two different modalities of extracorporeal bilirubin removal therapy for a pediatric patient. A 13-year-old boy with dilated cardiomyopathy requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) developed acute kidney injury and was dependent on continuous renal replacement therapy. He developed hyperbilirubinemia with a peak total bilirubin level of 786 µmol/L after implantation of biventricular assist device (BiVAD). Extracorporeal bilirubin and bile acids removal using single-pass albumin dialysis (SPAD) with 4% albumin as dialysate brought down the bilirubin level to 672 µmol/L after 21 h of therapy. Subsequently, he was started on two sessions of hemoadsorption using the Cytosorb® column which further lowered the total bilirubin level to 306 µmol/ in 24 h and 173 µmol/ after the treatment. No complication was encountered. Our case illustrated that both SPAD and hemoadsorption can effectively and safely reduce the serum bilirubin and bile acid levels in pediatric patients with BiVAD implantation. The ease of set-up, faster rate of bilirubin decline and capability of cytokine removal make hemoadsorption a favorable alternative to albumin dialysis.

Extracorporeal organ support and the kidney.

The concept of extracorporeal organ support (ECOS) encompasses kidney, respiratory, cardiac and hepatic support. In an era of increasing incidence and survival of patients with single or multiple organ failure, knowledge on both multiorgan crosstalk and the physiopathological consequences of extracorporeal organ support have become increasingly important. Immerse within the cross-talk of multiple organ failure (MOF), Acute kidney injury (AKI) may be a part of the clinical presentation in patients undergoing ECOS, either as a concurrent clinical issue since the very start of ECOS or as a de novo event at any point in the clinical course. At any point during the clinical course of a patient with single or multiple organ failure undergoing ECOS, renal function may improve or deteriorate, as a result of the interaction of multiple factors, including multiorgan crosstalk and physiological consequences of ECOS. Common physiopathological ways in which ECOS may influence renal function includes: 1) multiorgan crosstalk (preexisting or de-novo 2)Hemodynamic changes and 3) ECOS-associated coagulation abnormalities and 3) Also, cytokine profile switch, neurohumoral changes and toxins clearance may contribute to the expected physiological changes related to ECOS. The main objective of this review is to summarize the described mechanisms influencing the renal function during the course of ECOS, including renal replacement therapy, extracorporeal membrane oxygenation/carbon dioxide removal and albumin dialysis.

[Cardiogenic shock following yew needle poisoning : Digoxin immune fab, va-ECMO and albumin dialysis for the treatment of a suicidal yew leaf poisoning]. / Kardiogener Schock nach Eibennadelintoxikation : Digitalisantidot, va-ECMO und Albumindialyse in der Therapie der suizidalen Eibennadelintoxikation.

We present the case of a 46-year-old male who developed refractory bradycardia with cardiogenic shock after attempting suicide by ingestion of yew leaves. Due to delayed availability of the Digoxin immune fab, a va-ECMO was established to maintain sufficient circulation. Administration of the digoxin fab resulted in recovery of spontaneous circulation. Continuous venovenous hemodiafiltration with hemoadsorption and albumin dialysis were initiated with the intention to remove immune fab-toxin complexes and as organ support in acute kidney and liver failure. Within 5 days the patient was successfully weaned from ECMO, liver support and renal replacement and discharged without physical sequelae.

Extracorporeal Albumin Dialysis in Liver Failure with MARS and SPAD: A Randomized Crossover Trial.

INTRODUCTION: Liver failure is associated with hepatic and extrahepatic organ failure leading to a high short-term mortality rate. Extracorporeal albumin dialysis (ECAD) aims to reduce albumin-bound toxins accumulated during liver failure. ECAD detoxifies blood using albumin dialysis through an artificial semipermeable membrane with recirculation (molecular adsorbent recirculating system, MARS) or without (single-pass albumin dialysis, SPAD). METHODS: We performed a randomized crossover open trial in a surgical intensive care unit. The primary outcome of the study was total bilirubin reduction during MARS and during SPAD therapies. The secondary outcomes were conjugated bilirubin and bile acid level reduction during MARS and SPAD sessions and tolerance of dialysis system devices. Inclusion criteria were adult patients presenting liver failure with factor V activity <50% associated with bilirubin ≥250 µmol/L and a complication (either hepatic encephalopathy, severe pruritus, or hepatorenal syndrome). For MARS and SPAD, the dialysis flow rate was equal to 1,000 mL/h. RESULTS: Twenty crossovers have been performed. Baseline biochemical characteristics (bilirubin, ammonia, bile acids, creatinine, and urea) were not statistically different between MARS and SPAD. Both ECAD have led to a significant reduction in total bilirubin (-83 ± 67 µmol/L after MARS; -122 ± 118 µmol/L after SPAD session), conjugated bilirubin (-82 ± 61 µmol/L after MARS; -105 ± 96 µmol/L after SPAD session), and bile acid levels (-64 ± 75 µmol/L after MARS; -56 ± 56 µmol/L after SPAD session), all nondifferent comparing MARS to SPAD. CONCLUSION: A simple-to-perform SPAD therapy with equal to MARS dialysate flow parameters provides the same efficacy in bilirubin and bile acid removal. However, clinically relevant endpoints have to be evaluated in randomized trials to compare MARS and SPAD therapies and to define the place of SPAD in the liver failure care program.