Use of the molecular adsorbent recirculating system (MARS™) for the management of acute poisoning with or without liver failure.

INTRODUCTION

There is an increasing interest in recent developments in bioartificial and non-bioartificial devices, so called extracorporeal liver assist devices, which are now used widely not only to increase drug elimination, but also to enhance the removal of endogenous substances in acute liver failure. Most of the non-bioartificial techniques are based on the principle of albumin dialysis. The objective is to remove albumin-bound substances that could play a role in the pathophysiology of acute liver failure by dialysing blood against an albumin-containing solution across a high flux permeable membrane. The most widely used device is the Molecular Adsorbent Recirculating System (MARS™).

METHODS

The relevant English and French literature was identified through Medline using the terms, 'molecular adsorbent recirculating system', 'MARS', 'acute liver failure', 'acute poisoning', 'intoxication'. This search identified 139 papers of which 48 reported on a toxic cause for the use of MARS™. Of these 48 papers, 39 specified the substance (eighteen different substances were identified); two papers reported on the same group of patients. BIOARTIFICIAL AND NON-BIOARTIFICIAL SYSTEMS: Bioartificial systems based on porcine hepatocytes incorporated in the extracorporeal circuit are no longer in use due to the possibility of porcine retroviral transmission to humans. Historically, experience with such devices was limited to a few cases of paracetamol poisoning. In contrast, an abundant literature exists for the non-bioartificial systems based on albumin dialysis. The MARS™ has been used more widely than other techniques, such as the one using fractionated plasma separation and adsorption (Prometheus™). All the extracorporeal liver assist devices are able to some extent to remove biological substances (ammonia, urea, creatinine, bilirubin, bile acids, amino acids, cytokines, vasoactive agents) but the real impact on the patient's clinical course has still to be determined. Improvement in cardiovascular or neurological dysfunction has been shown both in acute liver failure and acute-on-chronic liver failure but no impact on mortality has been reported. ACUTE POISONING WITH LIVER FAILURE: Randomized controlled trials are very limited in number and patients poisoned by paracetamol or Amanita phalloides are usually included for outcome analysis in larger groups of acute liver failure patients. Initial results look promising but should be confirmed. Beyond its effect in liver failure, MARS™ could also enhance the elimination of the drug or toxin responsible for the failure, as is described with paracetamol. ACUTE POISONING WITHOUT LIVER FAILURE: Extracorporeal liver assist devices have also been used to promote elimination of drugs that are highly protein bound. Data in various case reports confirm a high elimination of phenytoin, theophylline and diltiazem. However, definite conclusions on the toxicokinetic or clinical efficacy cannot be drawn.

CONCLUSIONS

Despite the lack of large multicentre randomized trials on the use of MARS™ in patients with acute liver failure, the literature shows clinical and biological benefit from this technique. In drug or toxin-induced acute liver failure, such as paracetamol or mushroom poisoning, MARS™ has been used extensively, confirming in a non-randomized fashion, the positive effect observed in the larger population of acute liver failure patients. Furthermore, as MARS™ has been shown in experimental studies to remove protein-bound substances, it is potentially a promising treatment for patients with acute poisoning from drugs that have high protein-binding capacity and are metabolized by the liver, especially, if they develop liver failure concomitantly.