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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.

Intravenous lipid emulsion (ILE) has been proposed as a rescue therapy for severe local anesthetic drugs toxicity, but experience is limited with other lipophilic drugs. An 18-year-old healthy woman was admitted 8 h after the voluntary ingestion of sustained-release diltiazem (3600 mg), with severe hypotension refractory to fluid therapy, calcium salts, and high-dose norepinephrine (6.66 μg/kg/min). Hyperinsulinemic euglycemia therapy was initiated and shortly after was followed by a protocol of ILE (intralipid 20%, 1.5 ml/kg as bolus, followed by 0.25 ml/kg over 1h). The main finding attributed to ILE was an apparent rapid decrease in insulin resistance, despite a prolonged serum diltiazem elimination half-life. Diltiazem is a lipophilic cardiotoxic drug, which could be sequestered in an expanded plasma lipid phase. The mechanism of action of ILE is not known, including its role in insulin resistance and myocardial metabolism in calcium-channel blocker poisoning.

Many toxic agents induce brain dysfunction and/or lesions. Modern neuroimaging techniques, such as CT and more recently magnetic resonance imaging (MRI), are able to demonstrate toxic brain lesions at both early and delayed phases of disease progression. In the early phase, neuroimaging enables the detection of acutely injured brain areas responsible for sudden onset of neurological dysfunction, but the severity and the extension of brain lesions on neuroimages do not necessarily parallel the severity of the clinical status. In the chronic phase, when neurological dysfunction has become permanent, neuroimaging allows precise identification of neuroanatomical sequelae that do not necessarily match the severity of the chronic neurological impairment. Papers in the medical imaging literature have dealt mainly with the brain changes induced by 'chronic exposure' to toxic substances such as solvents or heavy metals. This article selectively reviews the main radiological changes observed on CT/magnetic resonance (MR) neuroimages after 'acute exposure' to industrial products (methanol [methyl alcohol], ethylene glycol), environmental agents (cyanide, carbon monoxide), pharmaceuticals (insulin, valproic acid) and illicit substances (heroin, cocaine). Different kinds of lesions, which lack specificity for toxic injury, can be observed on radiological images, but deep grey matter lesions with symmetrical distribution throughout basal ganglia are most often seen. However, such findings have also been reported after anoxic-ischaemic insults or during severe metabolic disturbances. Lesions in the white matter may also be present in the case of acute exposure to toxic agents. The true prognostic value of toxic-induced brain changes in the acute phase in CT or MR studies is unclear, although serial MRI may add new information as may quantitative or molecular imaging techniques such as the MR diffusion-weighted imaging or MR spectroscopy.

Objective: To report a case of a massive ingestion of ethylene glycol in an infant successfully treated by fomepizole without hemodialysis., Design: Descriptive case report., Setting: Pediatric intensive care unit., Patient: A 5-mo-old boy who ingested 200 mL of an antifreeze solution., Interventions: Antidotal therapy with a total of seven doses of fomepizole administered intravenously with an interval of 12 hrs (15 mg/kg as loading dose, then 10 mg/kg). Hemodialysis was not performed., Measurements and Main Results: Iterative determination of ethylene glycol concentration was obtained in blood and urine. Kinetics were calculated for ethylene glycol and fomepizole elimination. The infant made a complete recovery with no change in renal function., Conclusions: Although not yet approved for this indication in the child, fomepizole seemed safe and effective in a case of severe ethylene glycol poisoning, without the need for hemodialysis.

Background: There is an increasing gap between the number of patients on the waiting list and the number of transplanted patients. In France, more than 10000 patients waited for an organ transplantation in 2002. Due to the graft shortage, "marginal" donors are now considered. The patients who present brain death after accidental or voluntary poisoning belong to this category., Epidemiology: The data available from European or North American organ procurement organisations show that poisoned donors represent about 1% of all organ donors. It seems likely that a significant number of poisoned patients are not referred because poisoning is regarded as a contraindication to organ donation. When organ procurement can be achieved, the results expressed as recipient survival or graft survival are quite encouraging., Toxic Products: The most frequently involved toxins are either drugs (psychotropic agents, analgesics...), illicit substances, or environmental agents (gases, alcohols...). The literature data are discussed; some issues remain controversial., Practical Approach: Several criteria have to be applied when poisoned patients are considered as potential organ donors. Besides a firm diagnosis of "brain death", the knowledge of the "target organs" of poisoning is of paramount importance, together with careful analysis of the toxicokinetics and toxicodynamics. In most cases, routine biological and morphological data are sufficient to assess graft function.

Objective: To define specific brain magnetic resonance features in methanol intoxicated patients and to evaluate the clinical relevance of monitoring these features., Background: During the past decade magnetic resonance imaging has proven to be an exquisitely sensitive modality in depicting subtle water changes in diseased areas of the brain, allowing the definition of high-risk structures in numerous pathological conditions., Method: Four patients admitted to our institution for acute methanol intoxication were repeatedly evaluated by brain magnetic resonance imaging or a combination of computed tomography and magnetic resonance imaging. Common features of initial brain status were shown in all four cases and compared to those of patients presenting with other intoxications or critical deprivation states., Results: Preferential localization of methanol-induced lesions within the putamina was observed in all four cases. This finding is specific compared to intoxication by other substances like carbon monoxide, or in the critical phase of metabolic disorders. The striking regression of the putaminal lesions on follow-up magnetic resonance examinations correlated with complete neurological recovery and the absence of extrapyramidal disturbance. Two patients exhibited discrete symmetric additional lesions in the medial areas of the parieto-occipital lobes. In a third one, the occipital lesions were severe. All three suffered from permanent visual impairment. The fourth patient, in whom magnetic resonance examinations failed to reveal any occipital lesion, never complained of visual disturbance though signs of optic neuropathy were detected in the visual evoked potentials., Conclusion: Magnetic resonance imaging appeared as a well suited neuroimaging modality in methanol intoxicated patients both in revealing a specific pattern of brain lesions and in demonstrating valuable correlation between evolution of brain changes on magnetic resonance images and clinical outcome.

Case Report: An 86-year-old woman accidentally ingested a preparation containing zinc and copper sulfate. At ninety minutes after ingestion, the peak plasma concentration was 1979 micrograms/dL for zinc and 209 micrograms/dL for copper, suggesting preferential absorption of zinc. The major complications were gastric and bronchial inflammation due to the corrosive properties of these compounds. Systemic manifestations also developed with cardiovascular failure and renal insufficiency, but the patient made a complete recovery. In addition to symptomatic treatment, chelation therapy with dimercaprol and D-penicillamine was given for 48 h., Conclusion: The available clinical and toxicokinetic data do not support the benefits of chelation in addition to supportive therapy.

Experience with organ procurement from poisoned donors in brain death status is still limited in comparison with other etiologies. From 1963 to 1993, 2769 grafts (heart 141, kidney 1922, liver 623, pancreas 43) were performed in our University Hospital. Since 1975, among 1174 patients admitted to the ICU for acute poisoning, 12 patients who developed brain death status were considered for organ donation. The toxics involved were: methaqualone (1), benzodiazepines (1), benzodiazepines plus tricyclic antidepressants (2), barbiturates (2), insulin (2), carbon monoxide (1), cyanide (1), methanol (1), and acetaminophen (1). Exclusion criteria for organ removal were applied according to the nature of the toxin and the general criteria used for organ donation. The organs removed were: heart 5, heart valves for graft bank 2, kidneys 22, liver 4, pancreas 2, pancrease islet cells 2. Pertinent follow-up was obtained in 23 of 32 recipients. Immediate outcome was favorable in 20/23 patients (85%). Three patients died either from stroke, heart failure or preexisting encephalopathy. Two patients died from either chronic hepatic or renal graft rejection. None of these events could be directly related to a toxic origin. The one year survival rate of 75% is similar to that observed in the population who received organs from nonpoisoned donors. Organ procurement can be considered in few selected cases of acute poisoning. The accuracy of the diagnosis of irreversible brain damage is essential in this setting.

From 1975 to 1993, our University Hospital performed 2789 graft procedures. During the same period, 12 poisoned, "brain-dead" patients were considered as organ donors. The toxic substances involved were: methaqualone (n = 1), benzodiazepine alone (n = 1), benzodiazepine plus tricyclic antidepressants (n =1), tricyclic antidepressants alone (n = 1), barbiturates (n = 2), insulin (n = 2), carbon monoxide (n = 1), cyanide (n = 1), methanol (n = 1), and acetaminophen (n = 1). From these intoxicated persons, 32 organ transplants were obtained, but only 23 could be followed for 1 month and only 20 for 1 year. The outcome at 1 month was favorable in 20 of the 23 patients. Two heart transplant patients died with 24h after grafting from stroke and acute heart failure, respectively. Preoperative hepatic encephalopathy was not corrected after grafting and was directly responsible for the death of a liver transplant patient. After 1 year, 15 of the 20 recipients were still alive. Chronic hepatic graft rejection led to a fatal outcome in one recipient and to second grafting in another. Finally, one recipient died from delayed neoplasia. Based on our experience, organ procurement may be considered in a few select cases of acute poisoning. Attention should, however, be drawn to possible graft damage due to some poisons.

Cardiac arrhythmias and circulatory collapse account for the high mortality reported after severe chloroquine poisoning. We have recently observed a 17-year-old man who ingested an 8 g chloroquine overdose. Cardiac arrest occurred within 1 h. Cardiogenic shock was refractory to epinephrine, dopamine and molar sodium lactate. Amrinone, a bipyridine analog, was then successfully used to improve haemodynamic conditions.

A 26-year-old man suffered acute arsenic poisoning after a poisoning attempt. He developed multiple organ failure including encephalopathy, bleeding disorders, pancreatitis, renal and hepatocellular impairment. Generalized erythroderma also developed within one week after admission. The developed acute respiratory distress syndrome and Aspergillus fumigatus was isolated from the endotracheal aspirate. Despite intensive care support, antidote administration and various epuration techniques, the patient died on day 26 from subarachnoid bleeding. An autopsy was obtained and the concentration of arsenic was determined in different tissues. Multiple abscesses due to Aspergillus fumigatus were seen in the lungs, myocardium and kidneys. This uncommon complication in a previously immunocompetent patient could be related to impaired immunity directly caused by arsenic poisoning. [ABSTRACT FROM AUTHOR]