Factors contributing to mortality in paracetamol-induced hepatic failure.
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Biomedical subjects
Publications and source records attributed to B Widdop.
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Fifteen patients who were severely poisoned with either hypnotic drugs or salicylate were treated by charcoal haemoperfusion. The device contained 100g 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.
A haemoperfusion column containing activated charcoal coated with cellulose acetate was used to treat 7 patients with barbiturate or ethchlorvynol poisoning. Six of the patients showed marked lightening of coma and all showed a significant fall in plasma drug concentration. Plasma drug clearance and platelet loss were similar to those reported for other coated charcoal columns. Cellulose acetate-coated charcoal haemoperfusion may reduce the period of coma in severe poisoning with barbiturates and other hypnotic drugs and thus the morbidity and mortality.
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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.
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Five different hemoperfusion devices have been used in the treatment of patients, intoxicated with barbiturates. The changes in drug clearance values which occurred during hemoperfusion varied according to the device used. Even after very long periods of hemoperfusion, however, drug clearance values never fell to zero. Using data collected from comparable cases, it has been shown that the rate of uptake of drug from the blood is independent of the amount of adsorbent in the columns, those containing 100 gm charcoal having the same efficiency as the conventional 300 gm. The prime factor which determines the rate of drug uptake has been shown to be the arterial plasma drug concentrations. Other factors, such as the deposition of cellular debris and proteins as hemoperfusion progresses, are also thought to influence the efficiency of drug removal.
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Clinical and biochemical data obtained from 163 patients who had taken an overdose of paracetamol were examined to determine which factors or measurements were of value in predicting the severity of ensuing liver damage early after ingestion of tablets. Although the overall severity of hepatic necrosis was found to increase with the dose of paracetamol ingested, correlation was not sufficiently close to provide an accurate prognostic index in individuals. Severe hepatic damage was less likely if the patient had vomited or had a stomach wash-out within 6 hr of overdose. The plasma concentrations of paracetamol, measured at known times after overdose, distinguished those who developed hepatic dysfunction from those who did not, but there was a poor correlation, particularly in the first 6 hr after ingestion of tablets, between these values and the severity of ensuing liver damage. Estimates of early plasma paracetamol half-lives from three or more samples taken within 4 hr of admission showed that all patients developing moderate or severe liver damage had half-lives greater than 4 hr, but this was also the case in nearly one-third of those with minimal liver lesions only. It is concluded that there is no completely reliable early prognostic test for individual patients with paracetamol overdose. If each patient is selected for treatment with cysteamine (mercaptamine) or other agents on the basis of plasma paracetamol levels, up to 30% may receive this agent who are at risk from trivial hepatic damage only.
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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.