Theophylline & Caffeine Toxicity

Key Features

• Methylxanthines including theophylline and caffeine are nonselective adenosine receptor antagonists

• In overdose, toxicity results from the release of endogenous catecholamines with β₁- and β₂-adrenergic stimulation

• Theophylline

  • May cause intoxication after an acute single overdose or

  • Intoxication may occur as a result of chronic accidental repeated overmedication or reduced elimination resulting from liver dysfunction or interacting drug (eg, cimetidine, erythromycin)

  • Usual serum half-life of theophylline is 4–6 h; this may increase to > 20 h after overdose

• Caffeine in energy drinks or herbal or dietary supplement products can produce similar toxicity

Clinical Findings

• Mild intoxication

  • Nausea

  • Vomiting

  • Tachycardia

  • Tremulousness

• Severe intoxication (serum levels > 100 mg/L [555 mcmol/L])

  • Ventricular and supraventricular tachyarrhythmias

  • Hypotension

  • Seizures

• Status epilepticus is common and often intractable to usual anticonvulsants

• Symptoms may be delayed for hours after acute ingestion, especially if a sustained-release preparation was taken

• Serious toxicity may develop at lower levels (40–60 mg/L [222–333 mcmol/L]) with chronic intoxication

Diagnosis

• Serum theophylline concentration

• Hypokalemia, hyperglycemia, and metabolic acidosis are common after acute overdose

Treatment

• Activated charcoal

  • Give after acute ingestion

  • 60–100 g orally or via gastric tube, mixed in aqueous slurry

  • Do not use for comatose or convulsing patients unless it can be given by gastric tube and airway is protected by a cuffed endotracheal tube

  • Repeat doses may enhance gut decontamination and elimination by "gut dialysis"

• Consider whole-bowel irrigation for large ingestions of sustained-release preparations

• Indications for hemodialysis

  • Status epilepticus

  • Markedly elevated serum theophylline levels (eg, > 100 mg/L [555 mcmol/L] after acute overdose or possibly for levels > 60 mg/L [333 mcmol/L] with chronic intoxication)

• Treatment of seizures

  • Lorazepam, 2–3 mg intravenously

  • Diazepam, 5–10 mg intravenously

  • Phenobarbital, 10–15 mg/kg intravenously

  • Phenytoin is not effective

• Hypotension and tachycardia may respond to β-blocker therapy even in low doses

  • Esmolol, 25–50 mcg/kg/min by intravenous infusion

  • Propranolol, 0.5–1.0 mg intravenously

• Extracorporeal membrane oxygenation (ECMO) has been used successfully in patient with hemodynamic collapse after caffeine overdose