Christine Payen

Prothrombin time prolongation in paracetamol poisoning: a relevant marker of hepatic failure?

The association between paracetamol overdose and prolonged prothrombin time due to hepatic failure is well recognized. However, little is known of the possibility that paracetamol overdose can prolong the prothrombin time without overt hepatic failure. The few data from the literature suggest this is either due to a reduction in the functional levels of the vitamin K-dependent clotting factors by elevated doses of paracetamol, or a consequence of the administration of the antidote N-acetylcystein. The three reported cases provide further evidence that paracetamol overdose can be associated with a prolongation in the prothrombin time without overt hepatic failure. Even though the prothrombin time provides useful prognosis information, decisions regarding the management of these patients should not solely be based on this endpoint to avoid misinterpretation of the accuracy and the severity of liver failure.

Delayed toxicity following acute ingestion of valpromide

As valpromide is a prodrug of valproic acid (valproate), the clinical presentation of overdoses with either valpromide or valproate sodium is generally considered similar. Whereas plasma peak levels and signs of central nervous system depression occur within a few hours after the acute ingestion of regular-release forms of valproate sodium, delayed toxicity and time to peak levels following valpromide ingestion can be seen as shown by the three reported cases. They were initially considered as mild because patients presented with no or only moderate symptoms and serum valproate levels were below or at therapeutic levels on admission more than 3 hours post-ingestion in two of the three patients. Serum valproate levels were not monitored until marked deterioration more than 10 hours after ingestion. At the time of deterioration, serum valproate was at toxic level in the three reported cases. Therefore, large intake of valpromide should be closely monitored because no or moderate symptoms together with low plasma levels in the first few hours after ingestion do not exclude a subsequent severe intoxication. Despite the usual favourable outcome and the poor correlation between plasma levels and toxic symptoms, patients should not be discharged until plasma levels are documented to remain at low levels for at least 10 hours after the ingestion of valpromide and the patient asymptomatic.

Salbutamol misuse or abuse with fatal outcome: A case-report

Salbutamol is a short-acting agonist of the β2 adrenergic receptors sometimes misused or abused, which can result in various cardiovascular adverse effects. We report one case of fatal salbutamol misuse or abuse in a 36-year-old poorly controlled female asthmatic patient with a past medical history of alcoholism and a recent smoking cessation. She died shortly after hospital admission following acute dyspnea and sudden collapse at home. Toxicological analyses evidenced salbutamol overdose, and necropsy showed acute lung edema and marked dysplasia of the right ventricle and revealed the patient was pregnant. The involvement of an initial disorder of the ventricular rhythm leading to cardiac failure is suggested by the presence of several combined pro-arrhythmogenic factors, such as arrhythmogenic right ventricle dysplasia, hypoxemia related to bronchospasm and salbutamol overdose.

Intoxication by large amounts of barium nitrate overcome by early massive K supplementation and oral administration of magnesium sulphate

Suicide by ingestion of barium is exceptionally rare. Adverse health effects depend on the solubility of the barium compound. Severe hypokalemia, which generally occurs within 2 hours after ingestion, is the predominating feature of acute barium toxicity, subsequently leading to adverse effects on muscular activity and cardiac automaticity. We report one case of acute poisoning with barium nitrate, a soluble barium compound. A 75-year-old woman was hospitalized after suicidal ingestion of a burrow mole fumigant containing 12.375 g of barium nitrate. About 1 hour post-ingestion, she was only complaining of abdominal pain. The ECG recording demonstrated polymorphic ventricular premature complexes (VPCs). Laboratory data revealed profound hypokalemia (2.1 mmol/L). She made a complete and uneventful recovery after early and massive potassium supplementation combined with oral magnesium sulphate to prevent barium nitrate absorption.

Bone marrow aplasia following acute poisoning with chloroquine-proguanil.

Acute poisonings involving chloroquine are common in sharp contrast to those involving proguanil, another antimalarial drug. A 39-year-old woman ingested a combination of 11.2 g chloroquine and 22.4 g proguanil (i.e., 112 tablets of the commercial product Savarine®). She presented with cardiovascular disorders typically associated with chloroquine overdose, but unexpectedly bone marrow aplasia developed on day 3 post-ingestion that required granulocyte-colony stimulating factor administration, and recovered on days 10–14. Toxicological analysis evidenced both chloroquine and proguanil in the patients serum and ruled out the involvement of any major myelotoxic drug. This is seemingly the first report of bone marrow aplasia following acute poisoning with chloroquine and proguanil. The antifolinic effect of proguanil is hypothesized to have potentiated the still debated myelotoxicity of chloroquine in this patient.

Intoxication par le paracétamol chez la femme enceinte : à propos d’un cas

Severe but regressive toxic liver damage was observed in a 30-week pregnant woman due to acetaminophen poisoning. A cesarean section was performed 1 week later for suspected chorioamniotitis and the patient gave birth to an infant who only experienced complications of preterm birth. The lack of fetal liver damage following acute maternal paracetamol poisoning seems to be the rule, as shown by a review of the literature.

Acute Exenatide Overdose

Exenatide, a glucagon-like peptide-1 (GPL-1) receptor agonist, was quite recently approved as adjunctive therapy to improve glycemia control in type 2 diabetes patients. There is very limited information on overdose consequences. We report 3 cases of exenatide overdose involving 2 suicidal self-injections associated with psychotropic intake and one medication error. Two patients rapidly experienced gastro-intestinal symptoms and none of them presented severe hypoglycemia, which is in accordance with the known biological activity of GLP-1 that acts in a glucose-dependent manner and does not inhibit glucagon release in case of hypoglycemia. Interestingly one patient, who ingested large amounts of psychotropic drugs together with self-injection of a large dose (600 μg) of exenatide, presented unexpected delayed onset of central nervous system (CNS) symptoms whereas no hypoglycemia was experienced and no neurological feature is anticipated from exenatide exposure. Physicians should be aware of exenatide property to inhibit gastric emptying which can delay symptoms of acute poisoning due to co-ingested drugs.