SEVERE ACUTE ISONIAZID POISONING AND ANTIDOTAL MANAGEMENT IN A TOXICOLOGY CENTER IN URUGUAY

Resumo

INTRODUCTION: Isoniazid (INH) is a prodrug used in the treatment of tuberculosis, its acute toxicity can be severe with a mortality rate of 20%. Symptoms include refractory seizures, metabolic acidosis, and coma. In terms of pathophysiology, pyridoxine depletion affects GABA synthesis and leads to glutamate accumulation. A case of severe Isoniazid poisoning is described.  CASE REPORT: A 32-year-old man with a history of Substance Use Disorder (SUD) presented 7 hours after ingesting 24 g of INH (80 tablets of 300 mg), 3.6 g of ibuprofen, and 40 mg of tizanidine, along with smoked cocaine. In the emergency department, he was found to have tachycardia, hypertension (which progressed to hypotension), metabolic acidosis, hyperlactatemia, clonus, and generalized tonic-clonic seizures. He required mechanical ventilation and vasopressors. Late decontamination measures were initiated due to the severity and high number of tablets ingested, and he was treated with 15 g of pyridoxine along with benzodiazepines, with a favorable outcome.  DISCUSSION: The patient exhibited symptoms of severe toxicity, requiring specific treatment to reverse seizures. The seizures had a delayed onset - literature reports a range of 1.2 to 5 hours, whereas in this case, it was 7 hours. This latency before seizure onset may be linked to toxicokinetic factors due to the large number of tablets ingested and the concomitant use of other drugs. The patient also showed signs of serotonergic toxicity, which may be explained by INH’s monoamine oxidase inhibitor effect interacting with cocaine.  The dose of pyridoxine should be equivalent to the amount of INH ingested, up to a maximum of 15 g, which was the dose administered in this case. Seizures were managed with benzodiazepines, a strategy supported by the literature due to their synergistic effect on the GABA A receptor subunit.  This case highlights the importance of early recognition of INH poisoning and its treatment with pyridoxine in combination with benzodiazepines.