Single-pass Albumin Dialysis Research Articles

Role of single-pass albumin dialysis in acute-on-chronic liver failure of alcoholic origin: a single-center experience.

Role of single-pass albumin dialysis in acute-on-chronic liver failure of alcoholic origin: a single-center experience.

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

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

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

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. 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. 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. 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.

The application of hemoadsorption for hyperbilirubinemia and its impact on bilirubin removal kinetics in critically ill children.

Extracorporeal blood purification (EBP) is increasingly applied for bilirubin removal in critical care setting. We retrospectively reviewed the clinical features of children aged 1 month to 18 years old who received EBP for hyperbilirubinemia and explored the bilirubin removal kinetics by hemoadsorption (HA) in the pediatric intensive care unit of Hong Kong Children's Hospital from 3/2019 to 7/2022. Among the 14 episodes of EBP from six patients with a median age (interquartile range [IQR]) of 9.3(5.5) years old, 57.1% of them received HA, 33.3% received single-pass albumin dialysis (SPAD), and 7.1% received combined SPAD and HA. All HA episodes employed the Cytosorb® column. The median (IQR) pre-HA peak total bilirubin level was 406 (254) μmol/L. The saturation duration per HA episode was significantly shorter than the corresponding total treatment duration (8 vs 24 h, p = 0.012), and the median total and effective HA doses were 9.8(6.8) L/kg and 300.0 (163.4) mL/kg/h respectively. The overall bilirubin removal ratio by HA was 44.6 (14.5)%. A higher HA effective dose and a higher pre-HA bilirubin level were both associated with better bilirubin removal. No major EBP-specific complication was encountered. The liver enzymes showed improvement in all children. No patients required liver transplantation. There was no EBP-related mortality, but the overall PICU mortality of the cohort was 50%. HA was a safe and effective modality for bilirubin removal among children. Future studies should investigate the impact of bilirubin removal on clinical outcomes and explore the factors responsible for better removal efficacy.

Bio-Artificial Liver Support System: A Prospective Future Therapy

Whether acute or chronic, liver failure is a state of liver dysfunction that can progress to multiorgan failure. Mortality in liver failure patients is approximately 80–90% and is caused by detoxification failure, which triggers other immediate complications, such as encephalopathy, coagulopathy, jaundice, cholestasis, and acute kidney failure. The ideal treatment for liver failure is liver transplantation, but the long waiting period for the right donor match causes unavoidable deaths in most patients. Therefore, new therapies, such as tissue engineering, hepatocyte transplantation, and stem cells, are now being studied to anticipate the patient’s condition while waiting for liver transplantation. This literature review investigated the effectiveness of some bio-artificial liver support systems using review methods systematically from international publication sites, including PubMed, using keywords, such as bio-artificial liver, acute and chronic liver failure, extracorporeal liver support system (ECLS), MARS, single-pass albumin dialysis (SPAD). Artificial and bioartificial liver systems can show specific detoxification abilities and pathophysiological improvements in liver failure patients but cannot reach the ideal criteria for actual liver function. The liver support system must provide the metabolic and synthetic function as in the actual liver while reducing the pathophysiological changes in liver failure. Aspects of safety, cost efficiency, and practicality are also considered. Identifying the technology to produce high-quality hepatocytes on a big scale is essential as a medium to replace failing liver cells. An increase in detoxification capacity and therapeutic effectiveness must also focus on patient survival and the ability to perform liver transplantation.

Liver Support Devices: Bridge to Transplant or Recovery

Liver failure, whether acute or acute on chronic, is a devastating disease with a very high mortality and morbidity. The recent therapeutic advances, especially liver transplant, have given reason for optimism to the ever-rising population affected by this disease. However, scarcity of organs and lack of resources make this an option that only few can afford. The hunt for an artificial device to assist or replace the functions of the liver has been on the rise since the past 40 years. These devices are classified into artificial and bioartificial liver (BAL) assist devices. Artificial liver devices such as molecular adsorbent recirculating system, Prometheus, single-pass albumin dialysis, and selective plasma filtration therapy are mostly aimed at taking over the blood purification systems of the liver. BAL-assisted devices incorporate hepatic cell lines to obtain a more comprehensive coverage of the complex functions of the liver. These include extracorporeal liver assist device, modular extracorporeal liver support, HepatAssist, and Amsterdam Medical Centre-BAL. Development of an ideal liver assist device has been difficult due to the complexity of the functions of the organ. The initial studies on these devices are promising but inconclusive. Therapeutic plasma exchange seems to have a very favorable profile in the treatment of these patients and has been successfully used in a large number of patients. To arrive at a more definitive conclusion of the usefulness of these devices in the management of liver failure, large randomized multicentric studies with more objective end points need to be carried out. A literature review was performed using PubMed and library searches to collect the recent studies in this regard. This review aims to provide a myopic view of the advances that have been made in the development and usefulness of these liver assist devices.

Continuous renal replacement therapy under special conditions like sepsis, burn, cardiac failure, neurotrauma, and liver failure.

Continuous renal replacement therapy (CRRT) in sepsis does have a role in removing excessive fluid, and also role in removal of mediators although not proven today, and to allow fluid space in order to feed. In these conditions, continuous renal replacement therapy can improve morbidity but never mortality so far. Regarding sepsis, timing has become a more important issue after decades and is currently more discussed than dosing. Rationale of blood purification has evolved a lot in the last years regarding sepsis with the discovery of many types of sorbent allowing ideas from science fiction to become reality in 2021. Undoubtedly, COVID-19 has reactivated the interest of blood purification in sepsis but also in COVID-19. Burn is even more dependent about removal of excessive fluid as compared to sepsis. Regarding cardiac failure, ultrafiltration can improve the quality of life and morbidity when diuretics are becoming inefficient but can never improve mortality. Regarding brain injury, CRRTs have several advantages as compared to intermittent hemodialysis. In liver failure, there have been no randomized controlled trials to examine whether single-pass albumin dialysis offers advantages over standard supportive care, and there is always the cost of albumin.

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.

The use of a single pass albumin dialysis for the management of liver failure

Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.

Artificial liver support systems.

Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute-on-chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty-nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (-53μmol/L in MARS and -50μmol/L in SPAD), creatinine (-19.5μmol/L in MARS and -7.5μmol/L in SPAD), urea (-0.9mmol/L in MARS and -0.75mmol/L in SPAD), and gamma-glutamyl transferase (-0.215μmol/L·s in MARS and -0.295μmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.

Extracorporeal renal and liver support in pediatric acute liver failure.

The liver is the only organ which can regenerate and, thus, potentially negate the need for transplantation in acute liver failure (ALF). Cerebral edema and sepsis are leading causes of mortality in ALF. Both water-soluble and protein-bound toxins have been implicated in pathogenesis of various ALF complications. Ammonia is a surrogate marker of water-soluble toxin accumulation in ALF and high levels are associated with higher grades of hepatic encephalopathy, raised intracranial pressure, and mortality. Therefore, extracorporeal therapies aim to lower ammonia and maintain fluid balance and cytokine homeostasis. The most common and easily available modality is continuous kidney replacement therapy (CKRT). Early initiation of high-volume CKRT utilizing an anticoagulation regimen minimizing treatment downtime and delivering the prescribed dose is highly desirable. Ideally, extracorporeal liver-assist devices (ECLAD) should perform both synthetic and detoxification functions of the liver. ECLAD may temporarily replace lost liver function and serve as a bridge, either to spontaneous recovery or liver transplantation. Various bioartificial and biologic liver-assist devices are described in specialty literature, including molecular adsorbent recirculating system (MARS), single pass albumin dialysis (SPAD), and total plasma exchange (TPE); however, clinicians commonly use modalities easily available in intensive care units. There is a lack of standardization of indications for ECLAD, availability of different extracorporeal devices with varied technical approaches, and, of note, the differences in doses of ECLAD provided in clinical practice. We review the practicalities and evidence regarding these four artificial liver support devices in pediatric ALF.

Mutations in Myosin 5B in Children With Early-onset Cholestasis.

Mutations in Myosin 5B (MYO5B) are known to be associated with microvillous inclusion disease (MVID) a genetic cause of neonatal intractable diarrhoea. More recently, they have been reported in children with cholestasis but without typical gastrointestinal symptoms of MVID. We describe our series of children with cholestasis and mutations in MYO5B. Clinical, laboratory, and histological data were collected from patients with cholestasis and pathogenic mutations in MYO5B, found by next generation sequencing (NGS) but with minimal gastrointestinal disease. Six patients (3 boys) were identified. Median age at presentation was 19 months (range, 3-92). Presenting features were jaundice, pale stools, pruritus, and failure to thrive. Patients 5 and 6 had intractable diarrhoea until the age of 3 and 7 years, respectively, but currently are on full enteral diet with no intestinal symptoms. Median values for serum total bilirubin were 55 μmol/L (2-500), alanine aminotransferase 73I IU/L (32-114), γ-glutamyltransferase 7 IU/L (7-10), and serum bile acids 134 μmol/L (18-274). Three patients underwent 1 or more types of biliary diversion for symptom control. Median follow-up was 5 years (2-22). At most recent follow-up, they all reported pruritus while on antipruritics. Patient 1 had a liver transplant. We identified 6 patients, with mutations in MYO5B, early-onset cholestasis and pruritus, with variable response to biliary diversion without typical MVID.

Systematic review of artificial liver support systems: Current clinical challenges

Background: Artificial liver systems are used to bridge between transplantation or to allow a patient's own liver to recover. They are mainly used in patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF). Two examples include molecular adsorbent recirculating system (MARS) and single pass albumin dialysis (SPAD). The main aim of this study is to compare papers that have used MARS and SPAD to show which device is more efficient and a safer treatment. Material & Methods: A literature search was conducted using online libraries including; PubMed, Cochraine and EMBASE. Human publications after the year 2000 that were randomised control trials or comparative studies were included. A systematic review was completed and a comparison of the biochemical values was examined. There was also a comparison of the outcomes and any adverse effects that occurred. Result: 89 patients with ALF or ACLF were involved in this review, including 56 males and 33 females. Results showed that there was an average reduction in bilirubin (-68μmol/L in MARS and -59 μmol/L in SPAD), creatinine (-24 μmol/L in MARS and -2 μmol/L in SPAD), urea (-0.9mmol/L in MARS and -0/1 mmol/L in SPAD)and GGT (-0.26μmol/L.s in MARS and -0/46 μmol/L.s in SPAD) in both SPAD and MARS. However; there was no significant difference between the changes in the two systems. Conclusion: This systematic review proved that both MARS and SPAD are efficient at treating ALF and ACLF. However, there is no difference between efficiency of MARS and SPAD.There is a need for more large randomised control trials. Evaluating cost and patient preference would also help to differentiate the systems.

Single-Pass Albumin Dialysis in the Treatment of Children with Liver Failure

Background and Aims: Acute and acute on chronic liver failure are life-threatening conditions, and bridging to transplantation is complicated by a paucity of suitable organs for children. While different modalities of extracorporeal liver support exist, their use in children is complicated by a large extracorporeal volume, and data on their use in children is limited. The aim of this analysis was to investigate the efficacy and safety of single-pass albumin dialysis (SPAD) in children with liver failure. Methods: Retrospective medical chart review of pediatric patients with liver failure treated with SPAD. The decrease in hepatic encephalopathy (HE) and the serum levels of bilirubin and ammonia were measured to determine efficacy. Adverse events were documented to assess safety. Results: Nineteen pediatric patients with a median age of 25.5 months and a median body weight of 11.9 kg were treated with SPAD between January 2011 and March 2018. Total bilirubin (p < 0.001) and ammonia (p = 0.02) significantly decreased after treatment with SPAD. As clinical outcome parameter, HE significantly improved (p = 0.001). Twelve patients were bridged successfully to liver transplantation. In all patients, 71 SPAD sessions were run. Clotting in the dialysis circuit was observed in 49% of all sessions. Heparin and citrate were used for anticoagulation and were significantly superior to dialysis without any anticoagulation (p= 0.03). Transfusion of packed blood cells (57%) and catecholamine therapy (49%) were frequently necessary. Conclusions: Treatment with SPAD was effective in detoxification, as measured by significant improvement of HE and clearance from surrogate laboratory parameters.

Intermittent high‐flux albumin dialysis with continuous venovenous hemodialysis for acute‐on‐chronic liver failure and acute kidney injury

Acute-on-chronic liver failure (ACLF) requiring intensive medical care and associated with acute kidney injury (AKI) has a mortality rate as high as 90% due to the lack of effective therapies. In this study, we assessed the effects of intermittent high-flux single-pass albumin dialysis (SPAD) coupled with continuous venovenous hemodialysis (CVVHD) on 28-day and 90-day survival and an array of clinical and laboratory parameters in patients with severe ACLF and renal insufficiency. Sixteen patients were studied. The diagnosis of ACLF and AKI was made in accordance with current EASL Clinical Practice Guidelines, including the recommendations of the International Club of Ascites. All patients received SPAD/CVVHD treatments as the blood purification therapy to support liver, kidneys, and other organs. Five patients were transplanted and 11 were not listed for transplantation because of active alcoholism. Data at the initiation of SPAD/CVVHD were compared with early morning data after the termination of the extracorporeal treatment phase. All patients had ACLF and renal insufficiency with 13/16 additionally fulfilling the AKI criteria. A total of 37 SPAD/CVVHD treatments were performed [2.3±1.4]. The baseline MELD-Na score was 37.6±6.6 and decreased to 33.4±8.7 after SPAD/CVVHD (P<0.001). In parallel, the CLIF-C ACLF grade and OF score, estimated at 28- and 90-day mortality, AKI stage, hepatic encephalopathy grade, and liver function tests were lowered (P=0.001-0.032). The 28- and 90-day survivals were 56.2% overall and 53.8% in AKI. Survival in patients not transplanted (n=11) was 45.4%. In patients with severe ACLF and AKI, the renal replacement therapy coupled with high-performance albumin dialysis improved estimated 28- and 90-day survival and several key clinical and laboratory parameters. It is postulated that these results may be further improved with earlier intervention and more SPAD treatments per patient. High-performance albumin dialysis improves survival and key clinical and laboratory parameters in severe ACLF and AKI.

Organ replacement therapy - extracorporeal liver assist devices

Liver failure is a disease with a high mortality rate. Often liver transplantation is the sole therapeutic option. On the one hand, liver support systems probably support the liver to allow regeneration, on the other hand they are an option to bridge for transplantation. This article gives an overview on the clinically used liver assist devices (molecular adsorbent recirculating system [MARS], Prometheus system, single-pass albumin dialysis [SPAD], plasmapheresis) and discusses the applications in liver failure.

An Evaluation of the Usefulness of Extracorporeal Liver Support Techniques in Patients Hospitalized in the ICU for Severe Liver Dysfunction Secondary to Alcoholic Liver Disease.

BackgroundThe mortality rate in patients with severe liver dysfunction secondary to alcoholic liver disease (ALD) who do not respond to the standard treatment is exceptionally high.ObjectivesThe main aim of this study was to evaluate the usefulness of applying extracorporeal liver support techniques to treat this group of patients.Patients and MethodsThe data from 23 hospital admissions of 21 patients with ALD who were admitted to the department of anesthesiology and intensive therapy (A&IT) at the Dr Wł. Biegański Regional Specialist Hospital in Łódź between March 2013 and July 2015 were retrospectively analyzed.ResultsA total of 111 liver dialysis procedures were performed during the 23 hospitalizations, including 13 dialyses using fractionated plasma separation and adsorption (FPSA) with the Prometheus® system, and 98 procedures using the single pass albumin dialysis (SPAD) system. Upon admission to the intensive care unit (ICU), the median (interquartile range [IQR]) Glasgow coma scale (GCS), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II, and simplified acute physiology score (SAPS) II scores were 15 (14 - 15), 9 (7 - 13), 17 (14 - 24), and 32 (22 - 50), respectively. The ICU, 30-day, and three-month mortality rates were 43.48%, 39.13%, and 73.91%, respectively. As determined by the receiver operative characteristic (ROC) analysis for single-factor models, the significant predictors of death in the ICU included the patients’ SOFA, APACHE II, SAPS II, and model of end-stage liver disease modified by the united network for organ sharing (MELD UNOS Modification) scores; the duration of stay (in days) in the A&IT Department; and bile acid, creatinine and albumin levels upon ICU admission. The ROC analysis indicated the significant discriminating power of the SOFA, APACHE II, SAPS II, and MELD UNOS modification scores on the three-month mortality rate.ConclusionsThe application of extracorporeal liver support techniques in patients with severe liver dysfunction secondary to ALD appears justified in the subset of patients with MELD UNOS Modification scores of 18 - 30.

Single Pass Albumin Dialysis-A Dose-Finding Study to Define Optimal Albumin Concentration and Dialysate Flow.

Several artificial liver support concepts have been evaluated both in vitro and clinically. Single pass albumin dialysis (SPAD) has shown to be one of the most simple approaches for removing albumin-bound toxins and water-soluble substances. Being faced with acute liver failure (ALF) in everyday practice encouraged our attempt to define the optimal conditions for SPAD more precisely in a standardized experimental setup. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 mL/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 mL/h, whereas the albumin concentration was continuously kept at 3%. This study revealed that the detoxification of albumin-bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin-bound substances, from 350 mL/h to 700 mL/h (for bilirubin) or 1000 mL/h (for bile acids) of dialysate flow. Water-soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate. In conclusion, this study confirmed that SPAD is effective in eliminating albumin-bound as well as water-soluble toxins using a simulation of ALF. Furthermore, this project was successful in evaluating the most effective combination of albumin concentration (3%) and dialysate flow (700 mL/h-1000 mL/h) in SPAD for the first time.

Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure--a prospective, randomised crossover study.

BackgroundThe aim of extracorporeal albumin dialysis (ECAD) is to reduce endogenous toxins accumulating in liver failure. To date, ECAD is conducted mainly with the Molecular Adsorbents Recirculating System (MARS). However, single-pass albumin dialysis (SPAD) has been proposed as an alternative. The aim of this study was to compare the two devices with a prospective, single-centre, non-inferiority crossover study design with particular focus on reduction of bilirubin levels (primary endpoint) and influence on paraclinical and clinical parameters (secondary endpoints) associated with liver failure.MethodsPatients presenting with liver failure were screened for eligibility and after inclusion were randomly assigned to be started on either conventional MARS or SPAD (with 4 % albumin and a dialysis flow rate of 700 ml/h). Statistical analyses were based on a linear mixed-effects model.ResultsSixty-nine crossover cycles of ECAD in 32 patients were completed. Both systems significantly reduced plasma bilirubin levels to a similar extent (MARS: median −68 μmol/L, interquartile range [IQR] −107.5 to −33.5, p = 0.001; SPAD: −59 μmol/L, −84.5 to +36.5, p = 0.001). However, bile acids (MARS: −39 μmol/L, −105.6 to −8.3, p < 0.001; SPAD: −9 μmol/L, −36.9 to +11.4, p = 0.131), creatinine (MARS: −24 μmol/L, −46.5 to −8.0, p < 0.001; SPAD: −2 μmol/L, −9.0 to +7.0/L, p = 0.314) and urea (MARS: −0.9 mmol/L, −1.93 to −0.10, p = 0.024; SPAD: −0.1 mmol/L, −1.0 to +0.68, p = 0.523) were reduced and albumin-binding capacity was increased (MARS: +10 %, −0.8 to +20.9 %, p < 0.001; SPAD: +7 %, −7.5 to +15.5 %, p = 0.137) only by MARS. Cytokine levels of interleukin (IL)-6 and IL-8 and hepatic encephalopathy were altered by neither MARS nor SPAD.ConclusionsBoth procedures were safe for temporary extracorporeal liver support. While in clinical practice routinely assessed plasma bilirubin levels were reduced by both systems, only MARS affected other paraclinical parameters (i.e., serum bile acids, albumin-binding capacity, and creatinine and urea levels). Caution should be taken with regard to metabolic derangements and electrolyte disturbances, particularly in SPAD using regional citrate anti-coagulation.Trial registrationGerman Clinical Trials Register (www.drks.de) DRKS00000371. Registered 8 April 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1159-3) contains supplementary material, which is available to authorized users.

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM)

Peritoneal dialysis is the renal replacement therapy of choice for acute kidney injury in neonates, but in some cases is not feasible or effective. Continuous renal replacement therapy (CRRT) machines are used off label in infants smaller than 15 kg and are not designed specifically for small infants. We aimed to design and create a CRRT machine specifically for neonates and small infants. We prospectively planned a 5-year project to conceive, design, and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM), specifically for neonates and small infants. We created the new device and assessed it with in-vitro laboratory tests, completed its development to meet regulatory requirements, and obtained a licence for human use. Once approved, we used the machine to treat a critically ill neonate The main characteristics of CARPEDIEM are the low priming volume of the circuit (less than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via calibrated scales with a precision of 1 g. In-vitro tests confirmed that both hardware and software met the specifications. We treated a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration, single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's 65% fluid overload, raised creatinine and bilirubin concentrations, and severe acidosis were all managed safely and effectively. Despite the severity of the illness, organ function was restored and the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy. The CARPEDIEM CRRT machine can be used to provide various treatment modalities and support for multiple organ dysfunction in neonates and small infants. The CARPEDIEM could reduce the range of indications for peritoneal dialysis, widen the range of indications for CRRT, make the use of CRRT less traumatic, and expand its use as supportive therapy even when complete renal replacement therapy is not indicated. Associazione Amici del Rene di Vicenza.