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

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).

[The chemical toxicological determination of isoniazid and metoclopramide in the objects used for animals poisoning and in biological fluids]. / Khimiko-toksikologicheskoe opredelenie izoniazida i metoklopramida v ob''ektakh, ispol'zuemykh dlia otravleniia zhivotnykh, i v biologicheskikh zhidkostiakh.

The number of mass casualty incidents among the dogs has significantly increased during a few recent years in the cities of this country; they are most frequently attributed to the activities of the so-called dog hunters. The dog hunters make use of a variety of chemical compounds for poisoning the dogs. Most of them are the multi-component substances, with their chemical composition being highly variable and continuously modified. The objective of the present study was to develop the method for the isolation and identification of isoniazid and metoclopramide introduced into the baits that are distributed by the dog hunters for the poisoning of the animals. The proposed method was tested with the use of biological fluids obtained from the laboratory animals. The effectiveness of isolation of the compounds of interest from these materials with the use of the liquid-liquid and fractional freezing extraction techniques was evaluated. In addition, the method for solid phase extraction with the use of the 'Oasis HLB' cartridges was developed.

Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

BACKGROUND: Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. CASE PRESENTATION: A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge. CONCLUSIONS: Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting.

Near Fatal Poisoning by Isoniazid and Rifampicin.

Since six decades, Isoniazid and Rifampicin are used as first line drugs for treatment of tuberculosis. The minimum acute lethal or toxic dose of Rifampicin is not well established. However, non-fatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm and fatal acute overdoses with doses ranging from 14 to 60 gm. Isoniazid, if acutely ingested, even 1.5 to 2 gram may cause toxicity in adults. We report a case of Pott's spine on ATT, who took massive overdose of Rifampicin (>18 gm) and Isoniazid (>12 gm) and reported late (almost 36 hours) after ingestion. He was treated successfully with pyridoxine, hemodialysis and supportive care.

Antidotes to coumarins, isoniazid, methotrexate and thyroxine, toxins that work via metabolic processes.

Some toxins cause their effects by affecting physiological processes that are fundamental to cell function or cause systemic effects as a result of cellular interaction. This review focuses on four examples, coumarin anticoagulants, isoniazid, methotrexate and thyroxine from the context of management of overdose as seen in acute general hospitals. The current basic clinical pharmacology of the toxin, the clinical features in overdose and evidence base for specific antidotes are discussed. The treatment for this group is based on an understanding of the toxic mechanism, but studies to determine the optimum dose of antidote are still required in all these toxins except thyroxine, where treatment dose is based on symptoms resulting from the overdose.

Rhabdomyolysis due to isoniazid poisoning resulting from the use of intramuscular pyridoxine.

Isoniazid is an effective antituberculosis drug. Isoniazid poisoning produces a characteristic clinical syndrome that occurs 30 to 120 minutes after ingestion and includes seizures, metabolic acidosis, and in severe cases, coma. Rhabdomyolysis is one of the reported complications of isoniazid poisoning, but relevant data are limited. Parenteral pyridoxine is the antidote of isoniazid. In this case, a 16-year-old male patient admitted to the Pediatric Emergency Department two hours after isoniazid poisoning. For treatment, intramuscular pyridoxine was used, but he developed serious rhabdomyolysis.

Fatal suicidal poisoning with antituberculosis agents with ST elevation and acute coronary syndrome symptoms--a case report.

A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.

Toxic optic neuropathy.

Toxic optic neuropathy (TON) is a disease entity which is not only underdiagnosed, but also often diagnosed at a stage when recovery of vision is not possible. This article gives an overview of common causes, clinical features, and management of TON.

Isoniazid-induced status epilepticus in a pediatric patient after inadequate pyridoxine therapy.

BACKGROUND: Isoniazid (INH) is an effective treatment for tuberculosis and among the most common causes of drug-induced seizures in the United States. Isoniazid intoxication produces a characteristic clinical syndrome including seizures, metabolic acidosis, and, in severe cases, respiratory depression and coma. CASE: A 10-month-old male infant was presented after being found with his father's INH. The patient was brought to a local hospital where he had a witnessed generalized seizure and was given 650 mg pyridoxine intravenously, which was based on a 70 mg/kg recommendation. Five hours after the time of ingestion, the patient developed recurrent generalized seizures. He was given diazepam and then loaded with phenobarbital 20 mg/kg, while awaiting more pyridoxine from the pharmacy. He received an additional 2 g pyridoxine for a suspected ingestion of approximately 2.7 g INH (290 mg/kg total dose), and his seizures subsequently resolved. DISCUSSION: Treatment of INH toxicity must address correction of gamma-aminobutyric acid deficiency with pyridoxine replacement and management of life-threatening events. For poisonings in which the amount of INH ingested is known, pyridoxine is dosed on a gram-for-gram basis. Several reference textbooks recommend pyridoxine dosing in children to be 70 mg/kg. This was the justification for the initial pyridoxine dose administered in our case. However, after review of the referenced literature, the rationale supporting this recommendation remains unclear. Benzodiazepines should also be given with pyridoxine as they have been shown to have a synergistic effect in terminating seizures in animal models. CONCLUSIONS: As soon as possible after INH overdose is suspected or diagnosed, pyridoxine should be administered in a dose approximately equal to the estimated amount of INH ingested regardless of the age of the patient.

Liver transplantation for acute liver failure due to toxic agent ingestion in children.

ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow-up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post-operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.

Suicidal Isoniazid poisoning.

Accidental or intentional Isoniazid poisoning may manifest within half to three hours as intractable seizure, acidosis, and coma. Single high dose of pyridoxine was used as an antidote with good response as reported earlier. Ingestion of more than 80 mg/kg body weight produces severe central nervous system symptoms and a dose of 125 mg/kg is potentially lethal if not promptly treated. We report a case of suicidal attempt with use of Isoniazid, who developed grand mal seizures and was controlled with diazepam and symptomatic treatment.

Thoracic spine compression fracture during isoniazid-induced seizures: case report.

We report here an 11-year-old previously healthy girl with isoniazid intoxication who sustained a seizure-induced thoracic compression fracture. The following might be the first such case reported in the medical literature. Isoniazid toxicity should be suspected in any patient who comes to the emergency department with refractory seizures and metabolic acidosis. Forceful muscle contractions during a convulsive seizure can result in vertebral compression fracture, especially in the midthoracic region. A complaint of back pain after isoniazid-induced seizures in patients raises a strong suspicion of vertebral fracture and should be evaluated radiologically.

Coma caused by isoniazid poisoning in a patient treated with pyridoxine and hemodialysis.

Isoniazid is widely used to treat tuberculosis. In populations with a high prevalence rate of tuberculosis, acute ingestion of isoniazid has been reported as a potential cause of coma. In this study, we present the diagnosis and treatment of isoniazid poisoning in a case with acute coma as the major clinical presentation.A 32-year-old male who ingested 12 g isoniazid (2 hours prior to medical attention) was brought to the emergency department while in a coma and experiencing frequent seizures. Initial treatment with large doses of pyridoxine (for 6 hours) failed to awaken this patient. The patient was then given hemodialysis and pyridoxine; after 3 days he awoke from coma, with no further reported seizures.Isoniazid poisoning should be suspected in patients whose major symptoms are coma and seizure, especially those who have access to isoniazid. Monitoring the blood level of isoniazid will establish the diagnosis and help clinical management. A combination of hemodialysis and pyridoxine is effective in treating isoniazid poisoning.

Accidental isoniazid poisoning--a report.

Eight patients who had taken accidental overdose of Isoniazid were followed in relation to its clinical manifestations, EEG changes and management. All cases survived without any residual effect.