Transplacental transport of N-acetylcysteine in an ovine model.

STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy.

Lack of correlation between plasma 4-hydroxyglutethimide and severity of coma in acute glutethimide poisoning. A case report and brief review of the literature.

Glutethimide poisoning is characterised by coma, anticholinergic poisoning syndrome, hypotension, and other complications. Previous studies have shown that the severity of intoxication does not correlate with plasma glutethimide concentrations in individual patients. Glutethimide is partly converted to 4-hydroxyglutethimide, a metabolite which accumulates in the plasma of humans, and which has been thought to contribute to coma after plasma glutethimide concentrations have fallen. We followed plasma concentrations of glutethimide and 4-hydroxyglutethimide in a man who overdosed with glutethimide. Plasma 4-hydroxyglutethimide concentrations did not correlate with the degree of coma in our patient, and actually rose as the patient awakened. Other studies also indicate that 4-hydroxyglutethimide may not play an important role in glutethimide poisoning.

First-order elimination kinetics following baclofen overdose.

We followed serial plasma baclofen concentrations in a woman who ingested more than 2 g of baclofen in a suicide attempt, the largest ingestion of baclofen reported to date. The plasma clearance of baclofen was characterized by first-order elimination kinetics with a half-life of 8.6 hours. The persistent central nervous system depression noted in our patient after the return of plasma baclofen levels to the therapeutic range is best explained by delayed clearance of baclofen from the CNS. She made a full recovery with supportive care. No evidence of saturable elimination kinetics was found.