Sulfide toxicity: mechanical ventilation and hypotension determine survival rate and brain necrosis

Occupational exposure to hydrogen sulfide is one of the leading causes of sudden death in the workplace, especially in the oil and gas industry. High-dose exposure causes immediate neurogenic apnea and death; lower doses cause "knockdown" (transient loss of consciousness, with apnea). Because permanent neurological sequelae have been reported, we sought to determine whether sulfide can directly kill central nervous system neurons. Ventilated and unventilated rats were studied to allow administration of higher doses of sulfide and to facilitate physiological monitoring. It was extremely difficult to produce cerebral necrosis with sulfide. Only one of eight surviving unventilated rats given high-dose sulfide (a dose that was lethal in > or = 50% of animals) showed cerebral necrosis. Mechanical ventilation shifted the dose that was lethal in 50% of the animals to 190 mg/kg from 94 mg/kg in the unventilated rats. Sulfide was found to potently depress blood pressure. Cerebral necrosis was absent in the ventilated rats (n = 11), except in one rat that showed profound and sustained hypotension to < or = 35 Torr. Electroencephalogram activity ceased during exposure but recovered when the animals regained consciousness. We conclude that very-high-dose sulfide is incapable of producing cerebral necrosis by a direct histotoxic effect.