Brian Widdop

PARAQUAT POISONING: SIGNIFICANCE OF PLASMA-PARAQUAT CONCENTRATIONS

Plasma-paraquat concentrations were measured in 79 patients who had ingested liquid or granular weedkillers containing paraquat. At any given time after ingestion, the plasma-paraquat concentrations in the patients who died usually exceeded those in the survivors. It is suggested that measurement of plasma-paraquat concentrations is useful in assessing the severity and predicting the outcome of poisoning. Patients whose plasma concentrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg/l at 4, 6, 10, 16, and 24 h respectively are likely to survive.

HEPATIC DAMAGE AND DEATH FROM OVERDOSE OF PARACETAMOL

Abstract Of a series of sixty patients admitted after paracetamol overdose, forty-nine developed liver damage. Seventeen patients progressed to hepatic encephalopathy, and twelve of these died from fulminant hepatic failure. All but two of the patients with bilirubin levels above 4 mg. per 100 ml. by the 3rd-5th day developed encephalopathy. It is suggested that the degree and prognosis of the liver damage in the first few days can be assessed from the serum-bilirubin and prothrombin-time. Histology of liver-biopsy specimens of those who recovered showed severe centrilobular necrosis and collapse, but no patient has progressed to cirrhosis. Although most patients appear well in the first 3 days after ingestion, it is likely that the liver damage can be prevented only in the first 24 hours.

ORAL METHIONINE IN THE TREATMENT OF SEVERE PARACETAMOL (ACETAMINOPHEN) OVERDOSE

30 patients at risk of hepatic damage from paracetamol (acetaminophen) ingestion were given 2-5 g oral methionine every four hours up to a total dose of 10 g. The first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications. In 21 patients plasma aspartate-aminotransferase remained within normal limits. These results suggest that methionine may be effective in reducing the frequency and severity of paracetamol-induced liver damage and may provide an effective non-toxic alternative to cysteamine.

Experimental drug intoxication: treatment with charcoal haemoperfusion

Dogs were given large doses of barbiturates, glutethimide, ethanol, methaqualone, ethchlorvynol, meprobamate, chloral hydrate, paracetamol and aspirin. These were treated by haemoperfusion using a column packed with charcoal coated with an acrylic hydrogel. Clearances for most drugs were significantly higher than those reported for haemodialysis. Minimal clearances of common biochemical entities were observed and although leucocyte and platelet counts were diminished, no deleterious effects attributable to this were encountered. Careful histological examination of tissues derived from perfused dogs revealed no evidence of charcoal emboli.ZusammenfassungGrößere Mengen von Barbituraten, Glutethimide, Ethylalkohol, Methaqualone, Ethchlorvynol, Meprobamate, Chloral Hydrate, Paracetamol und Aspirin wurden Hunden verabreicht. Sie wurden sodann behandelt mit Häraoperfusion unter Benutzung eines Röhrchens, das mit Holzkohle gefüllt und mit einem Acryl-Hydrogel überzogen war. Bei den meisten Drogen war die Klärung bedeutend wirksamer als nach Berichten bei Behandlung mit Hämodialyse. Minimale Klärung von gewöhnlichen biochemischen Substanzen wurde beobachtet, und obgleich die Zahl von Leukocyten und Blutplättchen verringert war, zeigten sich keine darauf zurückzuführenden nachteiligen Effekte. Sorgfältige histologische Untersuchung von Geweben, die von in dieser Weise behandelten Hunden herrührten, zeigten keinen Befund von Kohleembolie.

Comparison of haemoperfusion and haemodialysis in the therapy of barbiturate intoxication in dogs

Dogs were given large doses of barbiturates. The effect of either haemoperfusion or haemodialysis was assessed and compared to treatment with supportive measures alone. Haemodialysis removed significant amounts of phenobarbitone, amylobarbitone and pentobarbitone, but haemoperfusion proved to be quantitatively superior both for these drugs and also for quinalbarbitone. This was also reflected by the clinical status of all three groups. Little or no disturbances in blood chemistry were observed, although platelet and leucocyte counts were diminished during haemoperfusion.ZusammenfassungHunde wurden mit hohen Dosen von Barbituraten vergiftet. Die Wirkung von Hämoperfusion oder Hämodialyse wurde mit der Behandlung durch herkömmliche Methoden verglichen. Die Hämodialyse entzog bedeutende Mengen von Phenobarbiton, Amylobarbiton und Pentobarbiton, aber die Hämoperfusion erwies sich sowohl für diese Substanzen als auch für Quinalbarbiton quantitativ überlegen. Dies zeigte sich auch im klinischen Zustand aller drei Gruppen. Wenige oder keine Störungen in der Blutchemie wurden beobachtet, obwohl bei der Hämoperfusion die Anzahl von Thrombocyten und Leukocyten absank.

Experience with fixed-bed charcoal haemoperfusion in the treatment of severe drug intoxication

SummaryFifteen patients who were severely poisoned with either hypnotic drugs or salicylate were treated by charcoal haemoperfusion. The device contained 100 g of activated charcoal immobilised by fixation to a polyester film. Two patients showed no response and eventually died. The remainder showed marked lightening of coma and recovered uneventfully. Complications of platelet loss and, in one patient, fibrinolysis were observed, but these had no serious consequences. No significant biochemical disturbances occurred with the exception of one patient who presented with hypocalcaemia and required intravenous calcium throughout the treatment. Drug clearance values were comparable with those obtained with columns containing 300 g of acrylic polymer coated charcoal.

The Use of Methionine for Acute Paracetamol Poisoning

Since September 1974 the London Centre of the National Poisons Information Service has advocated the use of methionine for acute paracetamol poisoning and this paper presents a preliminary report of its outcome. Seventeen patients, all of whom had high plasma paracetamol levels, received oral methionine within ten hours of the ingestion of the overdose. Eleven of these patients suffered no hepatic damage, while the remaining six showed varying degrees of liver failure with a mean maximum aspartate aminotransferase (AST) of 1,098 iu/l. There were no deaths in this group. Among fourteen patients who had taken similar paracetamol overdoses and received no antidotal treatment, all developed liver damage and seven of these died. These two groups were not, however, accurately matched for dose of paracetamol, plasma paracetamol levels or interval before reaching hospital. Comparison was therefore made with two other recently published series of untreated patients. A significant reduction was noted in the incidence of liver damage and in the mean maximum AST. Although this survey was not controlled, it is suggested that oral methionine, which has a low incidence of side-effects, may be effective in reducing the incidence and severity of paracetamol-induced liver damage, provided the overdose is not massive.

Rapid measurement of basic drugs in blood applied to clinical and forensic toxicology.

A gas chromatographic method is presented to measure blood, serum or plasma concentrations of more than 40 basic drugs. The sensitivity is 0·05 mg/L or less, which represents medium-high therapeutic and overdose concentrations, and in many instances the major active metabolites are also quantified. The paper describes a single step extraction from basic solution into n-butyl acetate containing maprotiline internal standard. Disposable glass tubes are used, with direct chromatography of the upper organic layer. GLC analysis is conducted for 10 min isothermally on a packed column (3% SP2250) with nitrogen-phosphorus detection. The coefficient of variation (CV) of the assay is between 2% and 5%, and data on the reproducibility of retention times are presented.

Fatal lignocaine poisoning: report of two cases and review of the literature

1 Two fatal cases of deliberate self-poisoning with lignocaine are reported, one by oral ingestion and one by intravenous injection. Post-mortem blood lignocaine concentrations were 40 and 53 mg/l, respectively. 2 Lignocaine self-poisoning is rare since no formulations for oral use other than gels are available. However, serious toxicity can follow the oral application or ingestion of such gels, especially in children and in the elderly. Fatalities due to accidental oral overdosage with 10-25 g of lignocaine in adults have also been reported. 3 The frequent incidental occurrence of lignocaine in specimens submitted for toxicological analysis should not exclude the possibility of poisoning with this compound.

Experience with activated carbon-bead haemoperfusion columns in the treatment of severe drug intoxication

Five patients who were severely poisoned with hypnotic drugs, paracetamol, or theophylline were treated by charcoal haemoperfusion. The device contained 160 g of activated carbon beads with a polyester coating. Four patients made a significant improvement; one subsequently died from a cerebral haemorrhage which had occurred prior to haemoperfusion. Platelet losses were minimal and no fibrinolysis was observed. No significant biochemical abnormality occurred as a result of haemoperfusion, although one patient, who presented with hypocalcaemia, required intravenous calcium throughout the procedure.