In a canine model of INH induced toxicity, pyridoxine reduced the severity of seizures, increased the duration of seizure free periods, and prevented death from a previously determined lethal dose of INH in a dose dependent fashion.13,14 Lower molar ratios prevented deaths, and higher molar ratios prevented both deaths and seizures.14 When used as single treatments for INH induced seizures, phenobarbital, pentobarbital, phenytoin, ethanol, and diazepam were ineffective in controlling seizures and death, but when combined with pyridoxine, each protected the animals from seizures and death.13 Other small animal experiments have documented the effectiveness of pyridoxine against MMH induced seizures when used without23,34,46 and with diazepam.20 Anticonvulsant efficacy is also demonstrated in feline42 and primate44 models.
Rat studies with intraperitoneal UDMH also demonstrate the protective effects of pyridoxine, which prevented seizures and death in a model that produced 94% mortality and 100% seizures without pyridoxine.15 Other studies in dogs and monkeys also demonstrate the effectiveness of pyridoxine in preventing seizures and mortality, and in treating seizures.4 Intramuscular pyridoxine protected the monkeys from death and stopped the seizures caused by IV exposure to UDMH.
Clinical experience with pyridoxine for INH overdose in humans demonstrates favorable results.2,11 Rapid seizure control with no morbidity or mortality was achieved when the ratio in grams of pyridoxine administered to INH ingested ranged from 0.14 to 1.3, although in practice, most patients receive approximately gram-for-gram amounts. In five patients, the use of gram-for-gram amounts of pyridoxine resulted in the complete control of seizures and a resolution of the metabolic acidosis.49 In eight patients with intentional INH overdoses, basic poison management, intensive supportive care, and a mean dose of 5 g of pyridoxine IV resulted in no fatalities.8 Seizures were controlled in a 22 month-old boy given 100 mg of IV pyridoxine after an estimated INH ingestion of 5 g.43 Variable results are reported when lesser amounts of pyridoxine are used.32 Seizures were reported in two patients after ingestion of INH–pyridoxine combination tablets, although the actual amount of pyridoxine ingested was not noted.45
In addition to controlling seizures, administration of pyridoxine also appears to restore consciousness. Two patients, who remained obtunded for as long as 72 hours after the apparent resolution of the seizures, were reported to awaken immediately after 3 to 10 g of IV pyridoxine was administered.10 A third patient who was lethargic awakened with IV pyridoxine. This suggests that mental status abnormalities associated with INH overdose (and possibly hydrazine overdoses) may be responsive to pyridoxine and may also require repetitive dosing.11,49 Patients treated with large doses of pyridoxine awaken more rapidly even after experiencing sustained seizure activity or status epilepticus.
Monomethylhydrazine poisoning can be encountered in a variety of clinical situations. In the aerospace industry, where MMH is used as a rocket propellant, percutaneous or inhalational poisoning may occur. Ingestion of the false morel mushroom, Gyromitra esculenta, can also produce toxicity when its major toxic compound, gyromitrin, is metabolized to MMH (Chap. 120).3,18
The neurologic effects of MMH poisoning are similar to those of INH toxicity and include seizures and respiratory failure.16 Severe liver damage similar to INH induced hepatotoxicity is also described.9 As in the case of INH induced hepatotoxicity, there is no evidence that MMH induced hepatotoxicity can be treated by administration of pyridoxine.9
A patient who was exposed to hydrazine became comatose 14 hours later and remained comatose for 60 hours until treated with 25 mg/kg of pyridoxine.25 A man with an altered consciousness who had ingested an unknown quantity of hydrazine improved after treatment with 10 g of pyridoxine.22 This improvement occurred over 24 hours and may have been unrelated to pyridoxine therapy. A severe sensory peripheral neuropathy lasting for 6 months developed one week after the overdose and was most likely a result of the hydrazine ingestion and not the pyridoxine. Six patients exposed to an Aerozine-50 (hydrazine and UDMH) spill were effectively treated with pyridoxine after developing twitching, clonic movements, hyperactivity, or gastrointestinal symptoms.19 A patient exposed to UDMH during an explosion developed extensive burns, diverse neurologic manifestations, and electroencephalographic findings that resolved rapidly after the administration of IV pyridoxine.17