Pyridoxine for the treatment of isoniazid-induced seizures in intentional ingestions: The experience of a national poison center

Glatstein, Miguel; Carbell, Gary; Scolnik, Dennis; Rimon, Ayelet; Banerji, Shireen; Hoyte, Christopher

doi:10.1016/j.ajem.2018.01.085

Cited by 10 publications

(6 citation statements)

References 18 publications

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“…Analysis limitations include the heterogeneous nature of our cohort, spanning 60 years, during which the standards of care have evolved: Only 42% of patients received a pyridoxine dose considered appropriate by modern standards, and many GABA A receptor agonists like benzodiazepines or propofol were not available in earlier reports. Mortality of patients treated with modern standard care, without ECTR, approaches 0% 2,38,39,42,43,58–60 (Tables 4 and 5) and occurs in patients who did not receive an appropriate pyridoxine dose or presented with severe toxicity 38,42 . Recurrence of seizures after appropriate pyridoxine is rare in historical cohorts 38,58 .…”

Section: Resultsmentioning

confidence: 99%

“…The net result is central neuroexcitation given that GABA is the major inhibitory neurotransmitter and glutamate is the major excitatory neurotransmitter 34,35 . Isoniazid poisoning manifests within 1–2 hours postingestion, characterized by metabolic acidosis, coma, seizures refractory to benzodiazepines and other anticonvulsants 36–39 hyperglycemia, and hyperkalemia 36,37,40 . Although isoniazid interferes with conversion of lactate to pyruvate, in animal studies acidemia does not occur without seizures and resolves within 2 h of seizure termination 41 …”

Section: Introductionmentioning

confidence: 99%

“…Prior to the use of pyridoxine, isoniazid poisoning mortality in large cohorts often exceeded 20%, 54–56 which decreased when pyridoxine was used more systematically 36,48,57 . With appropriate doses of pyridoxine, mortality from isoniazid poisoning is rare, unless patients present late to care 38,39,42,43,58,59 . The last four years of data from the American Association of Poison Control Centers’ National Poison Data System lists 497 single substance isoniazid exposures of which 135 were moderately or severely toxic, but no fatalities 60–63 …”

Section: Introductionmentioning

confidence: 99%

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Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

et al. 2021

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Isoniazid toxicity from self‐poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence‐based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty‐three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as “Moderately Dialyzable” by hemodialysis for patients with normal kidney function (quality of evidence = C) and “Dialyzable” by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

et al. 2021

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“…This enzyme is responsible for the production of GABA from glutamic acid or glutamate. Thus, we can attribute the pro-convulsive effect of isoniazid to its antigabergic effect by pyridoxine antagonism [27]. In addition, without the action of glutamic acid decarboxylase, glutamate levels, the main excitatory transmitter of the brain, are increased, favoring excessive neuronal firing.…”

Section: Isoniazidmentioning

confidence: 99%

“…In this case, the drug should be maintained on average up to two weeks after the carbapenem has been discontinued, and benzodiazepine is generally used [25]. In cases of seizures related to isoniazid, the lack of pyridoxine to produce GABA makes useless not only the use of drugs with no effect on GABAA receptors but also the inefficacy of gabaergic drugs, with indication of pyridoxine replacement [27]. In the event of crises caused by metronidazole in addition to its suspension, thiamine replacement is indicated.…”

Section: Treatmentmentioning

confidence: 99%

Seizures Related to Antibiotic Use: Update

Vilaça

Orsini

Martello

et al. 2018

BJSTR

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We did a non-systematic review of articles on the Google Scholar platform from January 1992 until February 2018.Preference was given to articles in Portuguese or English whose title presented the descriptors "seizures" or "epilepsy" associated with the most commonly used classes of antibiotics: penicillins, cephalosporins, quinolones, carbapenems, metronidazole and isoniazid. From this Abstract Objective: make a review about the risk of seizures related to the use of antibiotics. Method: We perform a non-systematic review using Google Scholar platform approaching the relationship between seizures and the most used antibiotics classes in clinical practice. Results and Discussion: 34 papers in English language were used for this review. Conclusion:Rarely antibiotics may cause seizures, mainly in patients with renal dysfunction, hepatic or previous brain disease. It is important to learn about drugs at greatest risk of seizures in each class of antibiotics. The treatment involves the use of correct medications, primarilygabaergic drugs, avoiding ineffective anticonvulsants.

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Isoniazid overdose

2018

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Pyridoxine for the treatment of isoniazid-induced seizures in intentional ingestions: The experience of a national poison center

Cited by 10 publications

References 18 publications

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Seizures Related to Antibiotic Use: Update

Isoniazid overdose

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