In this episode, I’ll discuss recent expert recommendations regarding the use of dialysis to treat isoniazid poisoning.
When taken in excess, isoniazid can cause severe toxicity, primarily in the form of seizure. Isoniazid inhibits pyridoxine metabolism and conversion of glutamate to GABA. This creates two problems that lead to excessive neuroexcitation and seizure. Glutamate levels are enhanced, and glutamate is the primary excitatory neurotransmitter. At the same time GABA levels are reduced, and GABA is the primary inhibitory neurotransmitter. The combination of more excitation and less inhibition leads to seizure and significant toxicity. These seizures are often refractory to benzodiazepines and other anticonvulsants.
Thankfully, high-dose pyridoxine is an effective treatment for isoniazid toxicity. The administration of high dose pyridoxine essentially eliminates mortality from isoniazid overdose, as long as the patient does not present late for treatment.
Limited supplies of pyridoxine and recent shortages have increased interest in using dialysis as a treatment for isoniazid toxicity. Isoniazid has a low molecular weight and low protein binding, making it theoretically an ideal candidate for removal by dialysis.
Recently the Extracorporeal Treatments in Poisoning workgroup presented a review of evidence on whether dialysis was an effective treatment for isoniazid toxicity.
The expert panel recommended against the routine use of dialysis for isoniazid toxicity for two reasons:
1. Most importantly, pyridoxine undergoes significant removal by dialysis, and this can be expected to undermine the ability of pyridoxine to terminate seizures.
2. The ability of dialysis to remove isoniazid drops significantly after just 2 hours post-ingestion. 75% of an IV dose of isoniazid is removed by dialysis if dialysis is started immediately, however, 2 hours after oral ingestion of isoniazid less than 20% of an oral dose of isoniazid is recovered.
The expert panel issued a recommendation against using dialysis to treat isoniazid toxicity, except in the rare case of inability to administer pyridoxine in a patient whose seizures are not controlled by benzodiazepines or other GABA modulators.
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