Felbamate overdose complicated by massive crystalluria and acute renal failure.

CASE REPORT: We report a 20-year-old woman who developed altered mental status, massive crystalluria, and acute renal failure following an intentional overdose of felbamate and sodium valproate. Peak plasma concentrations of felbamate and sodium valproate were 200 microg/mL and 470 microg/mL, respectively. Macroscopic urinary crystals formed approximately 18 hours after ingestion and were identified by gas chromatography as containing felbamate. Renal ultrasound revealed unilateral hydronephrosis. Following parenteral hydration, the crystalluria and acute renal failure resolved and the patient recovered. The frequency and significance of crystalluria in felbamate intoxication is unknown.

Epidemiology of poisoning.

Despite difficulties in the interpretation of available data, certain general observations can be made on the epidemiology of poisioning. Childhood poisoning is usually accidental and tends to be associated with a low morbidity and mortality. In Western Europe and North America, it is most often due to household products and pharmaceuticals; in developing countries, paraffin, traditional medicines , snakes bites and insect stings are more commonly involved. In adults, self-poisoning is usually deliberate (suicide or parasuicide) and has a higher morbidity and mortality rate. Analgesics and psychotropics predominate in Western Europe and North America as causes of admission to hospital, though carbon monoxide is responsible for most deaths (the majority of which occur outside hospital). In developing countries, accidental and deliberate pesticide poisoning is probably the commonest cause of adult deaths.

Use of N-acetylcysteine in clinical toxicology.

The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L-methionine also forms cysteine, thus giving rise to glutathione and other products. Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N-acetylcysteine infusion (20 hours intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N-acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed. N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2-dichloropropane, and other compounds. The possible use of N-acetylcysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research.

An introduction to the clinical toxicology of volatile substances.

Acute poisoning with organic solvents and other volatile compounds now usually follows deliberate inhalation (volatile substance abuse) or ingestion of these compounds. Solvents from adhesives, typewriter correction and dry cleaning fluids, cigarette lighter refills (butane) and aerosol propellants are commonly abused. The major risk is that of sudden death. Arrhythmias leading to cardiac arrest are thought to cause most deaths, but anoxia, respiratory depression and vagal stimulation leading to cardiac arrest may also contribute, as may indirect causes such as aspiration of vomit or trauma. In the United Kingdom (UK), 3.5 to 10% of young people have at least experimented with volatile substance abuse and mortality is more than 100 per annum. The products abused are cheap and readily available despite legislation designed to limit supply. Volatile substance abuse is not illegal and only a minority of abusers are known to progress to heavy alcohol or illicit drug use. Prevention of abuse by education, not only of children but also of parents, teachers, retailers and health care workers, is important in limiting the problem. However, volatile substance abuse-related deaths are still increasing in the UK despite many measures aimed at prevention. Clinically, volatile substance abuse is characterised by a rapid onset of intoxication and rapid recovery. Euphoria and disinhibition may be followed by hallucinations, tinnitus, ataxia, confusion, nausea and vomiting. It is important not to further alarm the patient if signs of serious toxicity are present, since a cardiac arrest may be precipitated. Further exposure should be prevented and the patient resuscitated and given supplemental oxygen if necessary. Cardiac arrhythmias should be treated conventionally and respiratory failure managed supportively. Long term exposure to n-hexane is associated with the development of peripheral neuropathy, while prolonged abuse (notably of toluene or chlorinated solvents) can cause permanent damage to the central nervous system, heart, liver, kidney and lungs. Knowledge of the routes of absorption, distribution and excretion of volatile compounds, and of the rates governing these processes, is important in understanding the rate of onset, intensity and duration of intoxication, and rate of recovery after volatile substance abuse. In addition, such knowledge is helpful when the clinician is attempting to interpret the results of toxicological analyses performed on samples (blood, other tissues, urine) from such patients. Many volatile substances are partly metabolised, the metabolites being eliminated in exhaled air or in urine. Although metabolism normally results in detoxification, enhanced toxicity may also result as with carbon tetrachloride, chloroform, dichloromethane, n-hexane, trichloroethylene and possibly halothane.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkaline diuresis for acute poisoning with chlorophenoxy herbicides and ioxynil.

The relation between blood chlorophenoxy herbicide and ioxynil concentrations and toxicity, and the effect of alkaline diuresis on outcome, have been studied in 41 patients. More than one herbicide was found in 38 cases. 6 of 30 patients who had ingested chlorophenoxy compounds alone died; 16 patients (mostly in grade 3-4 coma) had alkaline diuresis and 15 survived. 7 of 11 patients who had co-ingested ioxynil died; 3 had alkaline diuresis and all survived. Alkaline diuresis reduced plasma chlorophenoxy half-lives to values observed after doses that had no adverse effects (ie, below 30 h), but did not influence ioxynil clearance. Alkaline diuresis should be used to treat acute poisoning with chlorophenoxy herbicides or ioxynil in the presence of coma or other poor prognostic indicators, such as acidaemia, or if plasma total chlorophenoxy concentrations are 0.5 g/l or more.

Diagnosis and treatment of acute poisoning with volatile substances.

1. The acute toxicity of many volatile compounds is similar, being more related to physical properties than to chemical structure. 2. Volatile substance abusers experiences euphoria and disinhibition but this may be followed by nausea and vomiting, dizziness, coughing and increased salivation; cardiac arrhythmias, convulsions, coma and death occur in severe cases. 3. Laboratory analysis of blood and urine samples collected up to 24 h post-exposure may be helpful if the diagnosis of volatile substance abuse is in doubt. 4. There is only a weak correlation between blood toluene and 1,1,1-trichloroethane concentrations and the clinical features of toxicity, possibly because of rapid initial tissue distribution and elimination. 5. Recovery normally occurs quickly once exposure has ceased but support for respiratory, renal or hepatic failure may be needed as well as treatment for cardiac arrhythmias. Therapy with intravenous acetylcysteine should be considered in cases of acute carbon tetrachloride poisoning.

Paraquat poisoning: clinical features and immediate general management.

In contrast to 10-15 years ago most cases of paraquat poisoning are now due to deliberate self-poisoning with parasuicidal or suicidal intent rather than to accidental ingestion. Less commonly, poisoning may follow careless handling of paraquat during occupational use. Although paraquat can be absorbed through the skin if improperly handled, poisoning usually follows ingestion and has rarely been reported after subcutaneous, intravenous or intraperitoneal injection. Clinically, three degrees of intoxication may be distinguished. Mild poisoning occurs after the ingestion or injection of less than 20 mg of paraquat ion/kg body weight. In these cases patients are either asymptomatic or symptoms are confined to the gastrointestinal system. All patients recover fully. Moderate to severe poisoning usually follows the ingestion (rarely injection) of 20-40 mg of paraquat ion/kg body weight. Non-specific symptoms of ill health together with local gastrointestinal symptoms precede the development of renal failure (which may recover spontaneously) and pulmonary fibrosis which may not be manifest for days or weeks. Death occurs in the majority of cases but is usually delayed for 2-3 weeks. Acute fulminant poisoning follows the ingestion of substantial quantities of paraquat (greater than 40 mg of paraquat ion/kg body weight). In addition to local symptoms, multiple organ (cardiac, respiratory, hepatic, renal, adrenal, pancreatic, neurological) failure occurs. Death may supervene within hours and is never delayed for more than a few days. Initial general management has four priorities.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of paraquat poisoning in man: methods to prevent absorption.

Theoretically, absorption of an ingested dose of paraquat may be reduced by gastric lavage, induced emesis, whole-gut lavage or by the oral administration of absorbent substances. Animal experiments suggest that paraquat is absorbed poorly from the stomach and absorbed incompletely (less than 5%) from the small intestine over a 1-6 h period. Although gastric lavage would therefore seem a logical way to ameliorate the toxicity of an ingested dose of paraquat, peak plasma concentrations are attained rapidly and evidence for the efficacy of gastric lavage in man is poor. In 1977, a potent emetic (PP796) was added to liquid and solid formulations of paraquat because experiments in primates had demonstrated a fivefold reduction in toxicity. In man, ingestion of formulations containing an emetic is more likely to cause spontaneous vomiting within 30 min than non-emetic preparations. However, definite evidence of benefit, as judged by improved patient prognosis, has yet to be established. Gut lavage has been shown to remove only a small proportion of an ingested dose of paraquat. At the flow rates employed in man (75 ml/min), approximately 0.5-1.0 litres of lavage fluid/h may be absorbed across the intestinal wall. Since there is a theoretical risk of increasing paraquat absorption, the use of whole-gut lavage cannot be recommended. Bipyridilium herbicides are absorbed by soil and clay minerals, and montmorillonite in particular has been shown to be a strong binding agent in vitro. Accordingly, the use of Fuller's Earth (calcium montmorillonite) and Bentonite (sodium montmorillonite) for the treatment of poisoning has been investigated in animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute pesticide poisoning in England and Wales.

Between 1979 and 1983 less than 1% of admissions from acute poisoning in the UK were due to pesticides and fewer than 4% of admissions in those under 5 years were from this cause. Organochlorine, organophosphorus and carbamate insecticides account for only 10% of the total in both children and adults. Suspected pesticide poisoning was the cause of fewer than 0.3% of home accidents in those under 10 years of age and less than 4% of suspected poisonings documented by the Home Accident Surveillance System. Rodenticides were thought to be involved in 62% of these cases. Of children who presented to hospital 42% were admitted and 93% of these were discharged home within 2 days. In the UK, the morbidity from acute pesticide poisoning in children is low and the mortality is nil and there is therefore no evidence to support the view that paediatric pesticide intoxication is a significant clinical problem. Though no fatalities were recorded in children, pesticides were responsible for 1.3% of all deaths due to poisoning in the UK between 1979 and 1983. In adults admitted to hospital, the mortality from pesticide poisoning is approximately 12% and three quarters of these deaths are due to the deliberate ingestion of paraquat. The general term pesticide refers to a group of products that are used as insecticides, acaricides, fungicides, herbicides, rodenticides, and plant growth agents. Chemically, the group includes bipyridilium compounds, carbamates, chloralose, chlorates, coumarins, dinitro compounds, dithiocarbamates, fluoroacetates, organochlorine organophosphorus and organotin compounds, pentachlorophenol, phenoxyacetates, phosphine (as magnesium and aluminium phosphides), pyrethrins, pyrethroids and triazines.(ABSTRACT TRUNCATED AT 250 WORDS)