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CASE REPORT
Year : 1996  |  Volume : 50  |  Issue : 7  |  Page : 247-249
 

Management of isoniazid poisoning - Case report


Department of Medicine-III and Neurology, Patient B .D. Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana124 001, India

Correspondence Address:
A K Sood
Department of Medicine-III and Neurology, Patient B .D. Sharma Postgraduate Institute of Medical Sciences, Rohtak, Haryana124 001
India
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PMID: 8979544

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How to cite this article:
Sood A K, Dua A, Mahajan A. Management of isoniazid poisoning - Case report. Indian J Med Sci 1996;50:247-9

How to cite this URL:
Sood A K, Dua A, Mahajan A. Management of isoniazid poisoning - Case report. Indian J Med Sci [serial online] 1996 [cited 2013 May 21];50:247-9. Available from: http://www.indianjmedsci.org/text.asp?1996/50/7/247/11573


There are 15 to 20 million active cases of pulmonary tuberculosis, out of which 25% are sputum posi­tive cases. The prevalence of active disease in adults is 18 per 1000 population. The incidence of this disease is 2 to 3% per year. lsoniazid (INH) is the most com­monly used drug along with other cntitubercular drugs. [1] Intentional isoniazid overdose is an uncom­mon but well recognized problem in population having a high pre­valence of tuberculosis.

Although INH is considered quite safe in therapeutic doses, but when ingested in large doses, it decrea­ses the synthesis of inhibitory neurotransmitter GABA by inhibit­ing the pyridoxal phosphate depen­dent enzyme, glutamic acid decar­boxylase. [2] Features of acute in­toxication appear within 30 minutes of ingestion and include nausea, vomiting, dizziness and slurred speech. Major manifestations in­clude coma, generalized seizures. metabolic acidosis and death. [3] INH intoxication is a readily treatable condition and early and effective treatment can save the life. Pyri­doxine prevents a decrease in GABA concentration and is effec­tive in preventing seizures. Dia­zepam acts synergistically with pyridoxine in the control of ioni-azid induced seizures. INH is ef­fectively removed by hemodialysis also.

We report here a case of INH intoxication with status epilepticus who due to non-availability of in­jectable pyridoxine preparation, was given 10! gm of pyridoxine through a Ryle's tube and the pa­tient showed a quick and complete recovery.

Case Report : A 22 year old girl was admitted to the casualty department of Medical College Rohtak with the history of inges­tion of forty tablets of isoniazid 300 mg each (12 gm) with she in­tention of committing suicide. Shortly afterwards she developed severe nausea and vomited twice. Four hours later she started hav­ing continuous generalized tonic­-clonic seizures and was uncon­scious since then.

She was suffering from reactive depression for past six months as she was a case of bilateral extensive pulmonary tuberculosis for the last two years and had been taking antitubercular treatment irre­gularly. She was not taking any treatment for depression. There was no past history of seizures, trauma or jaundice.

At the time of admission the pa­tient was deeply comatosed and having frequent tonic clonic seizu­res. She was cyanosed with ton­gue-bite and labored breathing. She had moderate degree of pallor, slight edema of feet and there was no jaundice. Her pulse rate was 132/mt, regular, BP was 100/60 mmHg, respiratory rate was 32/mt and she was febrile (100.2°F). Pupils were mild-dilated and react­ing to light normally. Fundus exa­mination was normal. Systemic examination revealed bilateral ex­tensive coarse crepitations in the chest and bronchial breathing at the right apex. Cardiovascular sys­tem was essentially normal. Liver was palpable 2 cm below costal margin, non-tender. Spleen was 3 cm below costal margin, non-ten­der and there was no free fluid. CNS examination revealed a deeply comatosed patient without signs of meningeal irritation. Motor system examination reveal­ed a flaccid paralysis of all four limbs with bilateral extensor plan­tar response.

A stomach wash was carried out immediately after endotracheal in­tubation. Endobronchial suction was done repeatedly and 20 mg of diazepam was administered slow­ly intravenously over 10 minutes. She was also given oxygen though endotracheal tube. Ringer lactate and intravenous furosemide were given to force diuresis. In absence of availability of injectable pyrido­xine, a Ryle's tube was passed and she was given 5000 mg (125 tab­lets of 40 mg each) of pyridoxine through it immediately and ano­ther 5000 mg after one hour. Dia­zepam 10 mg iv. was repeated whenever needed. Within four hours of administration of pyri­doxine orally, seizure frequency reduced considerably but she was still comatosed. She regained con­sciousness after 24 hours, but had marked slurring of speech, nystag­mus and ataxia, from which she took about seven days to recover. She was seizure free afterwards.

On investigation, her hemoglo­bin was 7.5 gm%. Rest of her hematological and biochemical profile was normal. X-ray skull was normal and CT scan showed evi­dence of cerebral edema only. CSF examination was completely normal. X-Ray chest revealed bila­teral extensive fibro-cavitatory tuberculosis and sputum for AFB was positive. EEG done four hours later revealed diffuse high voltage delta and sharp spiky discharges along with evidence of seizural dis­charge, lasting for several seconds. A repeat done 24 hours later re­vealed diffuse high voltage delta and sharp spiky discharges, with­out evidence of seizural discharge. Blood gas parameters revealed evidence of mild metabolic acido­sis. She continued to improve and was given symptomatic treatment. She was also seen by a psychia­trist and was discharged seven days later with the advice to con­tinue antitubercular treatment. She made a complete recovery without any neurological residue.


 ¤ Discussion Top


Diagnosis of INH induced seizu­res is dependent on history and clinical circumstances, absence of previous history of seizures and complete relief of seizures after pyridoxine treatment. Ingestion of 15 gm or more is frequently fatal if untreated. [3]

Pyridoxine is given intravenously on the basis of 1 gm of pyridoxine for each gram of INH estimated to have been ingested. [2],[4],[5],[6] If the amount is unknown 5 gm of pyri­doxine intravenous is given at one time followed in 30 minutes by ad­ditional 5 gm. Sodium bicarbonate is given to correct metabolic acido­sis. Diazepam is used to control seizures. [2],[4]

Isoniazid should be prescribed with caution to those with a history of depression or suicidal tendency. Measures to prevent INH overdose include supervising drug admini­stration, dispensing small amounts of INH at one time and evaluating the patient compliance more often. [6]

This case again stresses the above-mentioned recommenda­tions to prevent INH toxicity. It also demonstrates the efficacy of oral pyridoxine in reversing this fatal emergency.


 ¤ Summary Top


A young girl was admitted with generalized tonic clonic seizures and unconsciousness, four hours after ingestion of 12 gm of isoni­azid (INH). In the absence of in­jectable preparation of pyridoxine, she was treated with oral pyrido­xine and made a complete re­covery.

 
 ¤ References Top

1.Udani PM. Tuberculosis in children. API text-book of Medi­cine 4th ed. Editor Shah SJ, Natio­nal Book Depot, Bomaby. 1986, 1091-1100.  Back to cited text no. 1      
2.Wason S, Lacouture P, Lovejoy FH Jr. Single high dose pyridoxine treatment for isoniazid overdose. JAMA 1981;246:1102-1104.  Back to cited text no. 2      
3.Brown CV. Acute isoniazid poison­ing. Am Rev Resp Dis 1972;105: 206-216.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Chin L, Sievers ML, Laird HE, et al. Evaluation of diazepam and pyridoxine as antidote to isonia­zid intoxication in rats and dogs. Toxicol Appl Pharmacol 1978:45; 713-722.  Back to cited text no. 4      
5.Katz KA, Jobin GC. Large doses of pyridoxine in the treatment of massive ingestion of isoniazid. Rev Resp Dis 1970;101:991-992.  Back to cited text no. 5      
6.Blanchard PD, Yao JDC, McAlpine DE, Hurt RD. Isoniazid overdose in the Cambodian population of Olmsted County, Minnesota. JAMA 1986:256:3131-33.  Back to cited text no. 6      




 

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