Seventeen patients received standard treatment with intravenous N-acetylcysteine for 18 episodes of severe poisoning with paracetamol (acetaminophen). The dose of N-acetylcysteine was 150 mg/kg given in 15 min followed by 50 mg/kg in 4 h and 100 mg/kg over the next 16 h. Liver damage was absent or mild on 13 occasions (ALT greater than 500 mu/l) and severe on 5 (ALT less than 1000 mu/l). Total plasma N-acetylcysteine was estimated by HPLC. The mean maximum plasma concentration after the initial loading dose was 554 mg/l. Concentrations then fell rapidly and after 12 h a mean steady-state level of about 35 mg/l was maintained. When the infusion was discontinued N-acetylcysteine disappeared with a half-life of 5.7 h. The mean steady-state volume of distribution, AUC, mean residence time and total clearance were 536 ml/kg, 1748 mg.h.l-1, 2.91 h and 3.18 ml.min-1.kg-1. These values are generally consistent with those previously reported with much smaller doses and the disposition of N-acetylcysteine does not appear to be dose-dependent. The elimination of N-acetylcysteine was not impaired in the patients with severe liver damage, and the pharmacokinetic variables and plasma concentrations were similar in patients with and without hepatotoxicity. The dosage schedule for intravenous N-acetylcysteine should probably be modified since adverse reactions invariably occur early when plasma concentrations are at their highest, and liver damage was prevented just as effectively at the lowest as at the highest Cmax. High initial concentrations of N-acetylcysteine can be avoided with simple alternative regimens based on the kinetic data of this study.

Anticholinergic activity is relevant for many medicinal and natural toxins. Delirium is a common consequence of toxicity. A direct antidote is available, but not often used. At one toxicology center, physostigmine continues to be employed in the emergency department and acute hospital setting. It is given 0.02 mg/kg IV at a rate of 0.5 mg/min with repeat doses q1-2h PRN. The following reports a 6-year retrospective review of the practice and a detailed prospective 1-year observational study of bedside use. One thousand one hundred and ninety seven patients were treated with physostigmine. The overall positive response rate was nearly 80%. The rate of arrhythmias was 0.17%; each event was self-limited. The rate of seizures was 0.75%; none resulted in significant sequelae. Cholinergic signs occurred in 6.4% of patients in prospective study; diaphoresis, nausea, emesis, and incontinence were all manageable. There were no cases of respiratory distress. The only documented adverse events in TCA cases were two episodes of diaphoresis out of 315 patients. Electrocardiographic abnormalities were not considered contraindications to physostigmine, and there were no serious adverse events regardless of QRS duration (72-168 msec) or QTc interval (341-662 msec). Physostigmine is a safe diagnostic and potentially therapeutic antidote for suspected toxic delirium.

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Lamotrigine toxicity manifested with minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and dopamine reuptake inhibition, and sodium channel blockade.