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PubMed2004

Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure: a meta-analysis.

Molecular adsorbent recirculating system (MARS) is an important option for patients with liver failure to give them additional time for recovery or to serve as a "bridge" to transplantation. However, its effect on survival for such patients is not well known. Our aim was to assess the treatment effects of MARS on patients with acute and acute-on-chronic liver failure. The outcomes measure evaluated was survival. We searched Medline (1966-2002) and EMBASE (1974-2002) using the terms liver failure, liver support systems, and MARS. Our search was extended to the Cochrane Controlled Trials Registry Database, published abstracts from 5 international conferences, Teraklin (the manufacturer of MARS), known contacts, and bibliographies from each full-published report. We included trials published in English and non-English languages. Eligible studies were randomized and nonrandomized controlled trials, which compared the treatment effects of MARS with standard medical treatment. Of the 206 articles screened, 4 randomized controlled trials including 67 patients were analyzed. Two nonrandomized trials with 61 patients were used for explorative analysis. The methodology, population, intervention, and outcomes of each selected trial were evaluated by duplicate independent review. Disagreements were resolved by consensus. In the primary meta-analysis, MARS treatment did not appear to reduce mortality significantly compared with standard medical treatment [relative risk (RR), 0.56; 95% confidence interval (CI), 0.28-1.14; P = .11]. Only 1 of the 4 randomized trials analyzed showed significant reduction in mortality. Sensitivity analysis of 3 peer-reviewed trials did not reduce mortality significantly with MARS treatment (RR, 0.72; 95% CI, 0.37-1.40; P = .33). Subgroup analysis of 2 trials for acute liver failure and another 2 trails for acute-on-chronic liver failure also did not reveal any benefit to survival with MARS treatment. In contrast, explorative analysis of 2 nonrandomized trials showed a significant survival benefit with MARS treatment (RR, 0.36; 95% CI, 0.17-0.76; P = .007). This was possibly related to bias in the selection of patients in the nonrandomized trials. In conclusion, MARS treatment had no significant survival benefit on patients with liver failure when compared with standard medical therapy. However, we found only a few trials with a small number of patients for the analysis, allowing for the possibility of false negative and erroneous conclusions. Well-conducted randomized trials are strongly recommended to define the role of MARS in the treatment of patients with liver failure.

Chronic Disease↗
PubMed2004

Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study.

The pathophysiological basis of acute-on-chronic liver failure (ACLF) is unclear but systemic inflammatory response is thought to be important. In patients with ACLF, the molecular adsorbents recirculating system (MARS) improves individual organ function, but the effect of MARS on the proposed mediators of systemic inflammatory response is unclear. The present study was designed to determine the effect of MARS on the cytokine profile, oxidative stress, nitric oxide, and ammonia. A total of 18 patients with alcohol-related ACLF due to inflammation-related precipitants were randomized to receive standard medical therapy (SMT) alone, or with MARS therapy over 7 days. Plasma cytokines, malondialdehyde (MDA), free radical production, nitrate / nitrite (NOx), and ammonia were measured. Encephalopathy improved significantly with MARS (P < .01), but not with SMT. Mean arterial pressure and renal function remained unchanged. No significant change of plasma cytokines and ammonia levels were observed in either group. Plasma MDA levels did not change either. There was a fall in NOx (P < .05) with MARS, but not with SMT. In conclusion, in inflammation-related ACLF patients, albumin dialysis using MARS results in improvement of encephalopathy, independent of changes of ammonia or cytokines, without improving blood pressure or renal function. These results should temper the liberal use of MARS until further data is available.

Adult↗
PubMed2003

The influence of lipophilicity and formulation on the distribution of pesticides in laboratory-scale sediment/water systems.

Pesticide reaching surface waters will be sorbed by sediment. This sorption process and the influence of pesticide formulation have been examined at 10 degrees C in small-scale systems having 2-cm depth of sediment and 8-cm overlying water stirred gently. Eight pesticides (triasulfuron, isoproturon, chlorotoluron, phenmedipham, difenoconazole, chlorpyrifos, pendimethalin and permethrin), spanning a range of physicochemical properties, were applied individually to the water. Sorption equilibrium was reached at between 15 and 30 days, the proportion of pesticide then in the sediment ranging from 20% for the acidic and therefore polar triasulfuron to 97% for the lipophilic permethrin; this behaviour was not influenced by formulation. Sorption coefficients measured in batch tests over 2 h gave good estimates of the equilibrium distribution. Some degradation was observed for all compounds over 90 days; for some compounds and formulations, enhanced degradation occurred after 20 to 60 days. It is concluded that lipophilicity is the chief determinant of pesticide distribution in sediment/water systems.

Algorithms↗
PubMed2004

Sorption of aged dicamba residues in soil.

The effect of aging (residence time in soil) on dicamba (3,6-dichloro-2-methoxybenzoic acid) and a major metabolite, 3,6-dichlorosalicylic acid (3,6-DCSA) sorption was determined in an unamended and a carbon-amended sandy loam and in a silt loam soil. During the incubation, sequential solvent extraction with 0.01 M calcium chloride solution and aqueous acetonitrile + hydrochloric acid was used to determine the solution and sorbed concentrations of dicamba and 3,6-DSCA, and sorption coefficients were calculated. Dicamba was weakly sorbed to soil (Kd < 0.7). In contrast to some other classes of pesticides, sorption of dicamba did not significantly increase with aging, at least not until < 15% of the applied dicamba remained. 3,6-DSCA was strongly sorbed to soil (Kd > 8) and the Kd-a value increased by a factor of 2-6 during a 28-day aging period. Addition of a carbon source to the soil had minimal effect on the strength of sorption of aged dicamba. However, it did appear to decrease 3,6-DSCA availability to soil micro-organisms; once formed 3,6-DSCA was not further mineralized. While it appears that sorption can be well characterized for weakly sorbed pesticides using the batch equilibration method with freshly treated soils, this procedure may not be adequate for more strongly sorbed pesticides and their degradates.

Biodegradation, Environmental↗
PubMed2004

Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs.

OBJECTIVE: Although water-soluble drugs can be removed by haemofiltration/haemodialysis, morbidity and mortality from intoxication with protein-bound drugs remains high. The present study investigates whether albumin dialysis in the form of the Molecular Adsorbents Recirculating System (MARS) is effective in removal of protein-bound drugs. DESIGN: Prospective animal study. SETTING: Surgical research laboratory in a university hospital. SUBJECTS: Seven female Norwegian Landrace pigs. INTERVENTION: We studied whether midazolam (97% albumin-bound) and fentanyl (85% alpha-1-acid glycoprotein-bound), administered as anaesthetics to pigs with induced acute liver failure, could be removed by MARS dialysis lasting for 4 h. MEASUREMENTS: After 4 h of dialysis, total and free anaesthetic concentrations were measured in the blood and dialysate from different segments of the MARS circuit. MAIN RESULTS: Midazolam: total plasma concentrations fell by 47.1+/-2.1% (in 4 h) across the MARS filter ( p<0.01). The charcoal component of the system reduced the total dialysate drug concentration by 16.4+/-2.2% ( p<0.05). Free midazolam removal followed a similar pattern. Fentanyl: total plasma concentrations fell by 56.1+/-2.4% (in 4 h) across the MARS filter ( p<0.01). Clearance of fentanyl from the dialysate by the charcoal was 70+/-0.7% at 4 h ( p<0.001). CONCLUSIONS: The results of the study show that MARS can remove both albumin and other protein-bound drugs efficiently from the plasma, and it may have a place for the treatment of patients suffering from intoxication with this class of compounds.

Anesthetics, Intravenous↗
PubMed2005

The effect of molecular adsorbent recirculating system on pathophysiological parameters in patients with acute liver failure.

OBJECTIVE: To investigate the effect of the molecular adsorbent recirculating system (MARS) on physiological variables in patients with acute liver failure. DESIGN: A prospective, observational study of MARS in addition to standard medical therapy in the management of patients presenting with acute liver failure. SETTING: A regional liver transplant centre. PATIENTS: Ten consecutive patients admitted with acute liver failure with a grade III or IV hepatic encephalopathy. INTERVENTIONS: MARS therapy for 8 h on 2 consecutive days. Standard monitoring included the use of a pulmonary artery catheter and an intracranial pressure monitor. MEASUREMENTS AND RESULTS: During the first MARS treatment there was a significant increase in systemic vascular resistance index (SVRI) from 1114+/-196 to 1432+/-245 dyne s(-1) cm(-5) m(-2) with a reduction in cardiac index from 5.5+/-0.6 to 4.2+/-0.4 l min(-1) m(-2). The changes were maintained between the start of the first and second sessions but not to the end of second. Significant clearance of urea and creatinine was observed. Intracranial pressure did not change during the treatments. Overall mortality was 70%. CONCLUSIONS: MARS therapy was well tolerated, with significant increases in vascular tone during the first session. This increase was not sustained over the duration of the study with a return to baseline values by the end of the second session. Based on our experience we cannot recommend the routine use of MARS therapy in acute liver failure outside of a clinical trial.

Adult↗
PubMed2006

Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation.

OBJECTIVE: To assess the usefulness of dialysis with the molecular adsorbent recirculating system (MARS) in patients with acute liver failure who fulfil criteria for liver transplantation. DESIGN: Observational cohort study. SETTING: ICU at a liver transplantation centre. PATIENTS: Twenty-two patients (23 episodes) received MARS dialysis. They were either listed for LT (n=14), delayed (n=1), or not listed (contra-indication, n=7). INTERVENTIONS: A total of 56 MARS treatments (median per patient 2; mean duration 7.6+/-2.6h) were performed on haemodialysis. MEASUREMENTS AND RESULTS: Clinical and biological variables were assessed before and 24[Symbol: see text]h after MARS therapy. The rate of recovery of liver function without transplantation was compared with an expected rate and survival was analysed. Following MARS dialysis, we observed an improvement in the grade of hepatic encephalopathy (P=0.02) and the Glasgow coma score (P=0.02), a decrease in conjugated bilirubin (P=0.05) and INR (P=0.006), and an increase in prothrombin index (P=0.005). Overall, liver function improved in seven patients (32%): four listed patients in whom transplantation could be avoided and three patients among those not listed due to contra-indications. The transplant-free recovery rate in listed patients was 29% (vs. expected 9%, P=0.036). Listed patients (n=14) had a higher 30-day survival rate [86% (12/14) vs 38% (3/8), P=0.05] and a higher long-term survival rate (P=0.02). CONCLUSIONS: A statistically significant improvement of liver function was observed after MARS therapy. Transplant-free recovery was more frequent than expected. The apparent benefit of MARS dialysis to treat acute liver failure needs to be confirmed by a controlled study.

Adult↗
PubMed2004

Value of albumin dialysis therapy in severe liver insufficiency.

A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.

Acute Disease↗
PubMed2006

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.

Adult↗
PubMed2006

Medical management of adolescent drug overdoses.

This article outlines the current clinical approach to poisonings in the adolescent age group. Management issues are presented for several specific substances frequently abused by this population. The purpose of such a review is to stimulate self-education in the practitioner. A secondary goal is to promote awareness of the various manifestations of substance abuse problems to facilitate recognition and referral. Adolescence is often a critical point for effective intervention and prevention on the road from use to addiction. Long-term survival may depend more on substance use rehabilitation than on the initial medical management.

Adolescent↗
PubMed2004

Bridges to transplantation.

The definitive treatment of patients with acute liver failure is liver transplantation. Organ Procurement and Transplantation Network status 1 patients receive priority, but the median waiting time in 2002 was 11 days. Patients who are small or have an unusual blood type are expected to wait even longer. Because cerebral edema and death may occur before a liver is available, numerous methods of bridging patients to transplantation by artificial means have been proposed. To date, no system of hepatic support has been proven effective at delaying the onset of cerebral edema in controlled trials.

Humans↗
PubMed2005

Molecular absorbent recirculating system for the treatment of acute liver failure in surgical patients.

The Molecular Adsorbent Recirculating System (MARS) represents an attractive artificial liver support system for the treatment of liver insufficiency. However, neither indications for MARS treatment (i.e., after extended liver resection) nor criteria for discontinuation of therapy have been evaluated. Therefore, we analyzed the clinical data of all our surgical patients who received MARS treatment for acute liver failure (n = 7). The aim of the study was to identify prognostic indicators for survival. Four of 174 patients resected for hepatic malignancy at our institution received a total of 13 MARS treatments. Two additional patients were successfully bridged to orthotopic liver transplantation with seven MARS treatments and one patient was MARS supported after liver transplantation of a steatotic graft with three MARS treatments. Five of the seven patients survived and were dismissed an average of 31 days, ranging from 17 to 47 days, after the final MARS treatment. No technical complications or adverse effects were observed during the MARS treatments. Important prognostic factors for hepatic recovery and survival were indocyanin green plasma disappearance rates greater than 5%/min and an increase in clotting factor V levels after each MARS treatment. We conclude that MARS therapy can be an effective treatment of postoperative liver insufficiency in the surgical hepatobiliary unit.

Adult↗
PubMed2006

Ion-imprinted beads for molecular recognition based mercury removal from human serum.

The aim of this study is to prepare ion-imprinted polymers which can be used for the selective removal of mercury ions [Hg(2+)] from human serum. N-Methacryloyl-(L)-cysteine (MAC) was chosen as the complexing monomer. In the first step, Hg(2+) was complexed with MAC and the Hg(2+)-imprinted poly(hydroxyethyl methacrylate-N-methacryloyl-(l)-cysteine) (MIP) beads were synthesized by suspension polymerization. After that, the template ions (i.e., Hg(2+)) were removed using thiourea (0.5%, v/v) in 0.05 M HCl. The specific surface area of the MIP beads was found to be 59.04 m(2)/g with a size range of 63-140 micro m in diameter and the swelling ratio was 91.5%. According to the elemental analysis results, the MIP beads contained 87.0 micro mol MAC/g polymer. The maximum adsorption capacity was 0.45 mg Hg(2+)/g beads. The applicability of two kinetic models including pseudo-first order and pseudo-second order model was estimated on the basis of comparative analysis of the corresponding rate parameters, equilibrium capacity and correlation coefficients. Results suggest that chemisorption processes could be the rate-limiting step in the adsorption process. The relative selectivity coefficients of MIP beads for Hg(2+)/Cd(2+), Hg(2+)/Zn(2+) were 14.7 and 21.5 times greater than the non-imprinted (NIP) matrix, respectively. The MIP beads could be used many times without decreasing in their adsorption capacities significantly.

Cations, Divalent↗
PubMed2006

Removal of arsenious ion by calcined aluminum oxyhydroxide (boehmite).

Aluminum oxyhydroxide (boehmite, BE) shows adsorption ability of arsenious ion. In this study, we calcined BE in the temperature range 200-1150 degrees C, and examined the amount of arsenious ion adsorbed and adsorption mechanism. As a result, the adsorption amount of arsenious ion by BE calcined at 400 degrees C showed the highest value as compared with those by BE calcined at other temperatures. On the other hand, the amounts of arsenious ion adsorbed onto BE showed lower values at 200, 600, and >1000 degrees C than that by BE before calcination. The amount of surface hydroxyl group of calcined BE showed the highest value at the calcination temperature of 400 degrees C. As a result of X-ray analysis, BE showed boehmite structure at less than the calcination temperature of 300 degrees C, while BE was converted to the transitional state of aluminum oxide at more than 400 degrees C. From the result of the amount of arsenious ion adsorbed and FT-IR, it turned out that calcined BE dissociated water molecule when suspended in the water, hydroxyl group was generated on the surface, and the amount of arsenious ion adsorbed was increased because of the ion exchange of these hydroxyl groups with arsenious ions. It was clarified that an adsorbent with high adsorption ability of arsenious ion was obtained by calcination of BE.

Adsorption↗
PubMed2004

Waste green sands as reactive media for groundwater contaminated with trichloroethylene (TCE).

Waste green sands are byproducts of the gray iron foundry industry that consist of sand, binding agents, organic carbon, and residual iron particles. Because of their potential sorptive and reactive properties, tests were conducted to determine the feasibility of using waste green sands as a low cost reactive medium for groundwater treatment. Batch and column tests were conducted to determine the reactivity, sorptive characteristics, and transport parameters for trichloroethylene (TCE) solutions in contact with green sands. Normalized rate constants for TCE degradation in the presence of iron particles extracted from green sands were found to be comparable to those for Peerless iron, a common medium used to treat groundwater. Rate constants and partition coefficients obtained from the batch tests were found to be comparable to those from the column tests. Analytical modeling shows that reactive barriers containing green sand potentially can be used to treat contaminated groundwater containing TCE at typical concentrations observed in the field.

Fresh Water↗