Toxin-Induced Neurologic Emergencies

David Lawrence, ... Christopher P. Holstege, in Clinical

Neurotoxicology, 2009
Organophosphates
Organophosphate poisoning may cause significant morbidity and
mortality due to seizure activity. Organophosphates (i.e., nerve
agents) induce seizures that progress through three stages. The first 5
minutes of exposure precipitates seizures due to cholinergic
overstimulation. During this period, agents with central anticholinergic
properties can abort or prevent these seizures. Beyond 5 minutes of
exposure, other changes are noted, such as decreased brain
norepinephrine levels, increased glutaminergic response, and NMDA
receptor activation. In this mixed cholinergic and noncholinergic stage,
anticholinergic treatment alone will not terminate seizures. Seizure
activity continuing 40 minutes after exposure is mediated by
noncholinergic mechanisms and results in structural neuronal injury
that is difficult to stop with pharmaceutical agents.58–60
When dealing with patients poisoned by organophosphates, it is
important to remember the effect of nicotinic overstimulation on the
neuromuscular junction. Patients may exhibit muscle fasciculations,
weakness, and frank paralysis. In this setting, seizures may not be
evident. Therefore, patients presenting with unresponsiveness and
flaccid paralysis after organophosphate exposure should be assumed
to be experiencing seizure activity until proved otherwise. 61Aggressive
management at stopping seizures (atropine and benzodiazepines),
electroencephalogram monitoring, and pralidoxime should be initiated
immediately in these cases.