theophylline overdose

Reactions 1279 - 21 Nov 2009

O STheophylline overdose

Severe toxicity in an elderly patient: case reportA 75-year-old woman developed severe (grade IV)

theophylline toxicity while receiving the drug for asthma,and later died [dosage and duration of treatment to reactiononset not stated]; her blood concentration was equivalentto a drug overdose.

The woman had a history of complete arrhythmia treatedwith amiodarone and vitamin K antagonists, chronicalcoholism, and asthma treated with theophylline.Emergency services were called after she sustained cranialtrauma from a fall; her consciousness was impaired, andshe had a recent history of vomiting and diarrhoea. She wasconvulsing on arrival of emergency services.

The woman’s seizure resolved with diazepam. She had aGlasgow Coma Scale (GCS) score of 3, and a glucose levelof 1.70 g/L; she gradually awoke in transit. On arrival at anemergency department, she had a GCS score of 11,tachycardia of 122/min, a stable BP of 126/75 and a bodytemperature of 37.9°C. Examination revealed full left-sidedhemiplegia, and later left-sided cloni, which wereterminated with clonazepam. Laboratory investigationsshowed the following: potassium 1.2 mmol/L, chloride82 mmol/L, magnesium 0.65 mmol/L, creatinine clearance30 mL/min and WBC count 15 × 109/L; her INR was > 10,consistent with vitamin K antagonist overdose. Arterialblood gas analysis on supplementary oxygen showed aPaCO2 of 10.4kPa, a PaO2 of 14.3kPa, a pH of 7.39, abicarbonate level of 45.5 mmol/L and a base excess of17.3 mmol/L. Sinus tachycardia with full right bundle-branch block was evident on ECG. Her plasma theophyllineconcentration was determined to be 51 mg/L (therapeutic:10–20 mg/L), consistent with an overdose. Chronictheophylline intoxication was diagnosed. EEG findingswere suggestive of non-convulsive status epilepticus withright-sided predominance; findings had not changed onrepeat EEG 24 hours later. A lumbar puncture aftercorrection of her INR was normal. She received potassiumand magnesium; thiopental and midazolam wereadministered under mechanical ventilation. Her EEGabnormalities resolved, but she experienced prolongedcoma. Other complications included ventriculartachycardia requiring cardioversion, shock requiringnorepinephrine [noradrenaline] administration, severalnosocomial infections and severe polyneuropathy.Following extubation, she experienced respiratory distressand impaired consciousness. It was decided to limit activetreatment measures, and she died after 2 months on lifesupport.

Author comment: In our case, the patient was sufferingfrom severe theophylline intoxication (level 4), with a guardedsurvival prognosis from the outset. . . The intoxication itselfwas responsible for an intracellular transfer of potassiumthrough stimulation of the Na-K pump ATPase of the musclecells. Furthermore, the digestive problems induced by theoverdose increased potassium depletion. Involvement ofpossible rhabdomyolysis in the renal failure was notinvestigated. . . The habitual administration of theophylline inthis elderly patient oriented diagnosis towards chronicintoxication.Guihard B, et al. Chronic theophylline intoxication. Journal Europeen desUrgences 22: 62-65, No. 2, Jun 2009 [French; summarised from a translation.] -France 801154579

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Reactions 21 Nov 2009 No. 12790114-9954/10/1279-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved