Albumin Dialysis Molecular Adsorbents Recirculating System: Impact of Dialysate Albumin Concentration on Detoxification Efficacy

Albumin dialysis with the molecular adsorbent recirculating system (MARS) or single pass albumin dialysis (SPAD) uses human serum albumin (HSA) as an addendum of the dialysate fluid. The purpose of this in vitro study was to evaluate the impact of the dialysate albumin concentration on removal efficacy. Heparinized human plasma (3 L/test) was spiked with creatinine (1000 mg/L), unconjugated bilirubin (100 mg/L), chenodeoxycholic acid (CDCA) (100 mg/L), and diazepam (3 mg/L). The MARS albumin circuit was primed with different amounts of HSA (150, 100, 60, and 40 g). The plasma, albumin, and dialysate flow rates were 200, 200, and 40 mL/min, respectively. Clearances were calculated based on repeated sampling during the experiments, which lasted 480 min. The effective HSA concentrations in the dialysate were 175, 115, 77, and 46 g/L, respectively. They decreased over treatment time to 147, 99, 63, and 41 g/L, respectively, due to surface adsorption. The plasma–HSA concentration remained unchanged over time in all experiments (average 39 g/L). The creatinine clearance was not impacted by dialysate HSA concentration. For the albumin‐bound markers a clear correlation between HSA‐concentration and clearance was demonstrated with the highest clearances for the 100 and 150 g HSA experiments. The 100 g HSA setup appeared to be the one with best cost–benefit ratio, resulting in clearances (after 1 h of treatment) of 31 mL/min creatinine, 0.3 mL/min unconjugated bilirubin, 11 mL/min CDCA, and 35 mL/min diazepam. Low albumin concentrations, such as in SPAD, result in low clearance rates for albumin‐bound substances. The optimal clearances in these experiments were reached with a priming dose of 100 g HSA.     

Improvement of Multiple Organ Functions in Hepatorenal Syndrome During Albumin Dialysis with the Molecular Adsorbent Recirculating System

Abstract: Recently, significant improvement of renal function and prolongation of survival were reported in hepatorenal syndrome (HRS) patients treated with the Molecular Adsorbent Recirculating System (MARS). As no impact on extrarenal organ function was documented, this trial looked into multiple organ function changes during MARS in HRS patients. Eight HRS patients (4 male, mean age 42. 1 years, range 30–58, all United Network for Organ Sharing [UNOS] status 2A) were treated intermittendly 4–14 times (total 47, mean 5.9 ± 3.4) between 4 and 8 h/single treatment. The following changes were observed pre‐ and posttreatment: bilirubin 466 ± 146 to 284 ± 134 γmol/L, creatinine 380 ± 182 to 163 ± 119 μmol/L, urea 26.4 ± 10.3 to 12.9 ± 4.9 mmol/L, plasma sodium 127.5 ± 7.7 to 137.5 ± 4.8 mmol/L (all p < 0.01). Mean arterial pressure (MAP) increased from 71.9 ± 12.8 to 95.6 ± 7.8 Torr (p < 0.001). Oliguria or anuria, present in all patients, was successfully reverted. Ascites, present in all patients, was not detectable after the treatment period. The hepatic encephalopathy grade decreased from 2.8 ± 0.8 to 0.8 ± 0.7 (p < 0.0001). Child‐Index decreased from 13.25 ± 1.3 to 9.4 ± 1.8 (p < 0.001). The hospital survival rate was 62%. One man underwent successful liver transplantation 18 months after the treatment. We conclude that MARS can improve multiple organ functions in patients with HRS.     

Predictive Criteria for the Outcome of Patients With Acute Liver Failure Treated With the Albumin Dialysis Molecular Adsorbent Recirculating System

The aim of this study was to evaluate the improvement of prognostic parameters after treatment with the molecular adsorbent recirculating system (MARS) in patients with fulminant hepatitis (FH). The parameters conducive to a positive prognosis include: Glasgow Coma Scale (GCS) score ≥11, intracranial pressure (ICP) <15 mm Hg or an improvement of the systolic peak flow of 25–32 cm/s via Doppler ultrasound in the middle cerebral artery, lactate level <3 mmol/L, tumor necrosis factor‐α <20 pg/mL, interleukin (IL)‐6 <30 pg/mL, and a change in hemodynamic instability from hyperkinetic to normal kinetic conditions, and so define the timing (and indeed the necessity) of a liver transplant (LTx). From 1999 to 2008 we treated 45 patients with FH with MARS in the intensive care unit of our institution. We analyzed all the parameters that were statistically significant using univariate analysis and considered the patients to be candidates for inclusion in a multivariate logistic regression analysis. Thirty‐six patients survived: 21 were bridged to liver transplant (the BLT group) and 15 continued the extracorporeal method until native liver recovery (the NLR group) with a positive resolution of the clinical condition. Nine patients died before transplantation due to multi‐organ failure. We stratified the entire population into three different groups according to six risk factors (the percentage reduction of lactate, IL‐6 and ICP, systemic vascular resistance index values, GCS <9, and the number of MARS treatments): group A (0–2 risk factors), group B (3–4 risk factors), and group C (5–6 risk factors). Analyzing the prevalence of these parameters, we noted that group A perfectly corresponded to the NLR group, group B corresponded to the BLT group, and group C was composed of patients from the non‐survival group; thus, we were able to select the patients who could undergo a LTx using the predictive criteria. For patients with an improvement of neurological status, cytokines, lactate, and hemodynamic parameters, LTx was no longer necessary and their treatment continued with MARS and standard medical therapy.     

Targeting Albumin Binding Function as a Therapy Goal in Liver Failure: Development of a Novel Adsorbent for Albumin Dialysis

Liver failure results in impaired hepatic detoxification combined with diminished albumin synthesis and is associated with secondary organ failure. The accumulation of liver toxins has shown to saturate albumin binding sites. This was previously demonstrated by an in vitro test for albumin binding capacity (ABiC) that has shown to inversely correlate with the established MELD (Model for End-Stage Liver Disease) score. In this study, we introduced a new adsorbent material for albumin dialysis treatments that improves albumin binding capacity. The new charcoal adsorbent was developed by an evolutionary test schedule. Batch testing of charcoals was performed as steady-state experiments. The charcoal reflecting the highest increase in albumin binding capacity was then introduced to kinetic models: Perfusion tests were designed to evaluate adsorption capacity and kinetics for liver failure marker toxins. A dynamic recirculation model for liver failure was used for upscaling and comparison against conventional MARS adsorbents as the gold standard in an albumin dialysis setting. Batch tests revealed that powdered activated Hepalbin charcoal displayed the highest ABiC score. Hepalbin charcoal also demonstrated higher adsorptive capacity and kinetics for liver failure marker toxins as determined by perfusion tests. These findings translated to tests of upscaled adsorbents in a dynamic model for liver failure: upscaled Hepalbin adsorbent removes bile acids, direct bilirubin and indirect bilirubin significantly better than MARS adsorbents and significantly increases ABiC. The novel adsorbent Hepalbin offers a significant improvement over both MARS adsorbents concerning liver failure marker toxin removal and ABiC improvement.     

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74‐month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration ≥15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48–1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (≥15 h) could be necessary to expect significant liver function improvement.     

Fulminant Hepatic Failure Bridged to Liver Transplantation with a Molecular Adsorbent Recirculating System: A Single-Center Experience

We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with a molecular adsorbent recirculating system (MARS), a cell-free albumin dialysis technique. From November 2000 to September 2002, seven adult patients ages 22–61 (median, 41), one male (14.2%) and six females (85.7%), affected by fulminant hepatic failure underwent seven courses (one to five sessions each, 6 hr in duration) of extracorporeal support using the MARS technique. Pre- and posttreatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies were reviewed. No adverse side effects such as generalized bleeding on noncardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while two (5%) recovered fully without transplantation. All the measured variables stabilized after commencement of the MARS. No differences were noted between the pre- and the post-MARS histology. We conclude that the MARS is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure.     

分子吸附再循环系统对多器官功能障碍综合征氧合功能的影响

目的 :研究分子吸附再循环系统 (MARS)对多器官功能障碍综合征 (MODS)患者氧合功能和血流动力学的影响。方法 :对 2 0 0 2年 11月至 2 0 0 3年 12月在我院ICU收治的 8例MODS患者 ,进行 2 9次床边MARS治疗有关资料进行回顾性分析和探讨。结果 :MARS治疗前后患者动脉血pH值无明显变化 ,但治疗后PaO2 、SaO2 及氧合指数 (PaO2 /FiO2 )均有显著改善 ,心率显著减慢 ,平均动脉压明显升高。结论 :MARS可改善MODS患者氧合功能及血流动力学指标     

Reduction of Elevated Cytokine Levels in Acute/Acute‐on‐Chronic Liver Failure Using Super‐Large Pore Albumin Dialysis Treatment: An In Vitro Study

The removal of small water soluble toxins and albumin‐bound toxins in acute liver failure patients (ALF) or acute‐on‐chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut‐offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super‐large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin‐bound toxins were removed more efficiently using novel large (Emic2) to super‐large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL‐6 and tumor necrosis factor‐α was drastically improved using super‐large pore membranes. The Emic2 membrane predominantly removed IL‐6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super‐large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.     

No Sustained Impact of Intermittent Extracorporeal Liver Support on Thrombocyte Time Course in a Randomized Controlled Albumin Dialysis Trial

Reduction of platelets is a common finding in patients with liver disease and can be aggravated by extracorporeal therapies, e.g. artificial liver support. The impact of extracorporeal albumin dialysis on the time count and time course of platelets in liver failure patients was evaluated in a randomized controlled clinical trial. Mean thrombocyte reduction during a single extracorporeal liver support therapy was ?15.1% [95%CI: ?17.7; ?12.5]. No differences were found between treatments of patients with a more reduced platelet count (<100 GPT/L: ?15.6% [?19.5; ?11.7%]; n = 43) compared to patients with normal or slightly decreased thrombocytes (?14.6% [?18.3%; ?11.0%]; n = 43; P = 0.719). The variation of platelet count within 24 h after onset of extracorporeal therapy treatment was less, albeit significant (?3.5% [?6.3%; ?0.7%], P < 0.016). Absolute thrombocyte variability was comparable between both groups (with extracorporeal therapy ?5.6 GPT/L [?9.7; ?1.4], without extracorporeal therapy ?1.3 GPT/L [?7.3; 4.7]; P = 0.243), whereas relative decrease of thrombocytes within a 24‐h period of extracorporeal therapy was greater than the changes in patients without extracorporeal therapy (?3.5% [?6.3%; ?0.7%] vs. 2.0% [?2.0%; 5.9%]; P = 0.026]. Within a period of two weeks after enrollment, no significant differences of platelet count were observed either between the two groups or in the time course (P_group = 0.337, P_time = 0.277). Reduction of platelets during intermittent extracorporeal liver support was less pronounced within a 24‐h period as before and after a single treatment and was comparable to variations in the control group without extracorporeal therapy.     

Early Molecular Adsorbents Recirculating System Treatment of Amanita Mushroom Poisoning

Acute poisoning due to ingestion of hepatotoxic Amanita sp. mushrooms can result in a spectrum of symptoms, from mild gastrointestinal discomfort to life‐threatening acute liver failure. With conventional treatment, Amanita phalloides mushroom poisoning carries a substantial risk of mortality and many patients require liver transplantation. The molecular adsorbent recirculating system (MARS) is an artificial liver support system that can partly compensate for the detoxifying function of the liver by removing albumin‐bound and water‐soluble toxins from blood. This treatment has been used in acute liver failure to enable native liver recovery and as a bridging treatment to liver transplantation. The aim of the study is to evaluate the outcome of 10 patients with Amanita mushroom poisoning who were treated with MARS. The study was a retrospectively analyzed case series. Ten adult patients with accidental Amanita poisoning of varying severity were treated in a liver disease specialized intensive care unit from 2001 to 2007. All patients received MARS treatment and standard medical therapy for mushroom poisoning. The demographic, laboratory, and clinical data from each patient were recorded upon admission. The one‐year survival and need for liver transplantation were documented. The median times from mushroom ingestion to first‐aid at a local hospital and to MARS treatment were 18 h (range 14–36 h) and 48 h (range 26–78 h), respectively. All 10 patients survived longer than one year. One patient underwent a successful liver transplantation. No serious adverse side‐effects were observed with the MARS treatment. In conclusion, MARS treatment seems to offer a safe and effective treatment option in Amanita mushroom poisoning.     

Is It Possible to Gain Extra Waiting Time to Liver Transplantation in Acute Liver Failure Patients Using Albumin Dialysis?

Hepatic encephalopathy (HE)‐associated brain edema is a common cause of death in acute liver failure (ALF). Molecular Adsorbent Recirculating System (MARS) albumin dialysis detoxifies endogenous and exogenous toxins from blood and improves HE. In this study we assessed the effect of MARS on increasing the length of time available while waiting for liver graft. Thirty‐seven patients with ALF who received a high‐urgent liver transplant (LTx) were divided into three groups according to the amount of histological necrosis in the explanted liver: group I = 100% necrosis; group II = 80–99% necrosis; group III = less than 80% necrosis. MARS was used continuously until LTx. Median time (range) on MARS treatment prior to LTx in groups I–III was 7 days (2–26), 6 days (1–17), and 5 days (1–15), and the median time on the waiting list was 5 days (1–11), 3 days (0–13), and 1 day (0–12), respectively. The HE grade prior to and after MARS was similar in all groups. In two patients the HE grade decreased during MARS treatment, even though the explanted liver showed a complete lack of viable cells. Overall 30‐day and one‐year survival were 97% and 92%, respectively, without differences between the three groups. In ALF patients the liver cell damage progressed to total or near total necrosis of the liver when the waiting time was prolonged. Yet, with MARS treatment some patients with total hepatic necrosis showed an absence of encephalopathy. With MARS treatment some patients might be able to wait longer for a LTx with good results.     

Effect of Extracorporeal Liver Support by Molecular Adsorbents Recirculating System and Prometheus on Redox State of Albumin in Acute‐on‐Chronic Liver Failure

Oxidative stress is believed to play an important role in acute‐on‐chronic liver failure (AoCLF). Albumin, an important transport vehicle, was found to be severely oxidized in AoCLF patients. Extracorporeal liver support systems may exert beneficial effects in AoCLF via removal of albumin‐bound toxins. At present, two systems are commercially available, the molecular adsorbents recirculating system (MARS) and fractionated plasma separation, adsorption and dialysis (FPAD, also known as Prometheus). The aim of this study was to compare the effect of MARS and Prometheus treatments on the redox state of human serum albumin. Eight patients with AoCLF underwent alternating treatments with either MARS or Prometheus in a randomized cross‐over design. Sixteen treatments (eight MARS and eight Prometheus) were available for analysis. The fraction of human mercaptalbumin (HMA), human nonmercaptalbumin‐1 (HNA1), and human nonmercaptalbumin‐2 (HNA2) were measured before and after single MARS and Prometheus treatments and during follow‐up. In AoCLF patients the oxidized fractions of albumin, HNA1, and HNA2 were markedly increased. Both MARS and Prometheus treatments resulted in a shift of HNA1 to HMA, while HNA2 was not significantly affected. This shift in albumin fractions was transient and disappeared within 24 h after treatment. There were no significant differences between MARS and Prometheus treatments with respect to the redox state of albumin. Both MARS and Prometheus treatments lead to transient improvements of the redox state of albumin, which could be beneficial in the treatment of AoCLF.     

Molecular Adsorbent Recirculating System: clinical experience in patients with liver failure based on hepatitis B in China

Abstract: The aim of this study is to evaluate the effect of treatment with the Molecular Adsorbent Recirculating System (MARS) on liver failure based on HBV. In 25 patients (median age, 36.3 years, range, 22–67 years, bilirubin level > 255 µmol/l) admitted with liver failure based on HBV, the 6–8h MARS intermittent treatments were performed without any adverse events, A significant decrease in bilirubin, ammonia and urea levels were observed (P < 0.05). All patients achieved a remarkable neurologic recovery, particularly 2 HE-III and 3 HE-IVpatients regained normal consciousness, respectively. The survival rate for the patients whose treatments kept to the MARS art strategy was 76.9% (10/13), while the others only had the survival rate of 16.7% (2/12) due to their giving up sequential MARS treatments after the first time. The rebounding rate of the bilirubin level in the patients after a single MARS treatment was significantly lower than that of patients, who underwent a single plasma-exchange treatment (P < 0.01). It is concluded that MARS method can contribute to the optimistic treatment of liver failure patients based on HBV which being the major epidemic liver disease in China.     

Application of Molecular Adsorbent Recirculating System® in patients with severe liver failure after hepatic resection or transplantation: initial single-centre experiences

Abstract: Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS®) that allows detoxification of albumin-bound substances and may hereby support liver regeneration and patient's recovery has been developed. In the present study, we report our experiences with MARS® dialysis in patients with liver failure after hepatic resection or transplantation. Between September 1999 and January 2001, five patients were treated with MARS® (2–5 courses). Though beneficial effects such as improvement of encephalopathy and renal function as well as reduced bilirubin levels were recorded during MARS® therapy, only one patient survived. Neither significant technical problems nor adverse effects occurred by using MARS® dialysis. We conclude that in surgical patients, acute liver failure is usually part of a complicated clinical course affecting multipleorgan systems. Thus, it is difficult to determine the specific influence of MARS® on patient's outcome. However, beneficial effects observed in our patients justify its continuous use and may stimulate further evaluation in controlled studies with surgical patients.     

Artificial liver support system in China: a review over the last 30 years

Severe viral hepatitis with high mortality is the most common cause of liver failure in China. Treatment of severe viral hepatitis by hemoperfusion was initially adopted in the late 1970s and early 1980s. Following 10 years of development in China, a plasma exchange (PE)-centered artificial liver support system (ALSS), principally dependent on PE technology was developed. Based on the condition and symptoms of each patient, PE was given alone, or combined with hemodialysis, hemofiltration, hemodiafiltration, hemoperfusion, or plasma perfusion. In the late 1990s, training courses for ALSS were developed, and ALSS began to be carried out across China. Guidelines for artificial liver therapy were formulated and published by the Artificial Liver and Liver Failure Group of the Chinese Society of Infection. In recent years, new methods have been attempted, including small pore-size plasma separators, a molecular adsorbent-based recirculating system (MARS), and a continuous albumin purification system (CAPS). According to a retrospective analysis published in 2004, ALSS therapy significantly (P < 0.001) improved the survival rate of patients with severe hepatitis compared with patients who received only medicines (43.4%, 157/362 vs. 15.4%, 55/358 in chronic patients and 78.9%, 30/38 vs. 11.9%, 5/42 in acute and subacute patients). Furthermore, ALSS has also proved valuable as a bridge to liver transplantation in the treatment of patients with end-stage severe hepatitis in China. More recently, ALSS has been used in the treatment of drug-induced liver failure, acute fatty liver during pregnancy, and other difficult-to-treat disorders in China.     

Role of Apheresis and Dialysis in Pediatric Living Donor Liver Transplantation: A Single Center Retrospective Study

In the field of pediatric living donor liver transplantation, the indications for apheresis and dialysis, and its efficacy and safety are still a matter of debate. In this study, we performed a retrospective investigation of these aspects, and considered its roles. Between January 2008 and December 2010, 73 living donor liver transplantations were performed in our department. Twenty seven courses of apheresis and dialysis were performed for 19 of those patients (19/73; 26.0%). The indications were ABO incompatible‐liver transplantation in 11 courses, fluid management in seven, acute liver failure in three, renal replacement therapy in two, endotoxin removal in two, cytokine removal in one, and liver allograft dysfunction in one. Sixteen courses of apheresis and dialysis were performed prior to liver transplantation for 14 patients. The median IgM antibody titers before and after apheresis for ABO blood type‐incompatible liver transplantation was 128 and eight, respectively (P < 0.05). Eleven courses of apheresis and dialysis were performed post liver transplantation for 10 patients. The median PaO2/FiO2 ratio before and after dialysis for fluid overload was 159 and 339, respectively (P < 0.05). No bleeding or technical complications attributable to apheresis and dialysis occurred. The 1‐year survival rate of the patients was 100%. Apheresis and dialysis in pediatric living donor liver transplantation are effective for antibody removal in ABO‐incompatible liver transplantation, and fluid management for acute respiratory failure.     

Effect of treatment with the Molecular Adsorbents Recirculating System on arterial amino acid levels and cerebral amino acid metabolism in patients with hepatic encephalopathy

Background: Liver failure is associated with low concentrations of branched‐chain amino acids and high concentrations of most other amino acids. In this study the effect of treatment with the Molecular Adsorbents Recirculating System (MARS) on arterial amino acid levels and cerebral amino acid metabolism was examined in patients with severe hepatic encephalopathy. Methods: The study included seven patients with hepatic encephalopathy from fulminant hepatic failure (FHF) and five patients with hepatic encephalopathy from acute‐on‐chronic liver failure (AoCLF). Cerebral blood flow and cerebral arteriovenous differences in amino acids were measured before and after 6?h of treatment with MARS. Results: During MARS treatment, the total arterial amino acid concentration decreased by 20% from 8.92?±?7.79?mmol/L to 7.16?±?5.64?mmol/L (P?P?Conclusions: MARS treatment tends to normalize the arterial amino acid concentrations in patients with hepatic encephalopathy. Even though the overall reduction in plasma amino acids and improvement in amino acid dysbalance may well be beneficial, it was not accompanied by any immediate improvement in cerebral amino acid metabolism in patients with FHF or AoCLF.     

Molecular Adsorbent Recirculating System (MARS®) removal of piperacillin/tazobactam in a patient with acetaminophen‐induced acute liver failure

The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS^®). The patient was a 32‐year‐old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin‐enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein‐bound toxins. In addition to protein‐bound waste, MARS removes water‐soluble, low molecular‐weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k_e) for the removal of piperacillin in this patent was 0.453 h^?1 and the half‐life (λ) was 1.53 h. The k_e was 2.9‐fold higher than with CVVHD alone and the λ was 3.7‐fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.     

A 3‐year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion

Abstract In our 3‐year experience, we treated 63 patients with Molecular Adsorbent Recirculating System (MARS). The patients were divided as follows: 10 primary non‐function (PNF) 16%, 10 delayed non‐function (DNF) 16%, 16 Fulminant hepatitis (FH) 24%, 23 acute decompensation of chronic liver disease (ACLF) 38%, and 4 hepatic resection 6%. All patients who underwent MARS treatment had bilirubin >15 mg/dL, Glasgow Coma Score between 9 and 11, ammonium >160 µg/dL and non‐coagulability. The determining factors taken into consideration for the continuation of MARS treatment were: an improvement in Glasgow Coma Score, and a decrease in ammonium and bilirubin. We also monitored hemodynamic parameters, acid–base equilibrium, and blood gas analysis before and after each treatment. In order to determine patients' neurological conditions, we not only took into account the Glasgow Coma Score, which does not give mathematically precise results but also took into account the fact that patients with hepatic coma had lower cerebral mean velocity in the cerebral arteries than patients without encephalopathy. For this reason, in the last 22 patients we monitored cerebral perfusion, determined by mean flow velocity (V_mean) in the middle cerebral artery. Our results were expressed as mean ± SD and we analyzed the differences between mean values for each variable, before and after treatment by means of Student's t‐test. At the end of treatment, we obtained significant P‐values for bilirubin, ammonium, Glasgow Coma Score and creatinine. In 16/20 patients, we could demonstrate a clear correlation between the improvement in clinical conditions (especially neurological status) and improvement in cerebral perfusion, measured by color Doppler US.