Updated 1/2004

 

Features:

Mild/moderate toxicity:
Nausea, vomiting (which is often severe and resistant to standard antiemetics, epigastric pain, haematemesis and pancreatitis. Tachycardia, tremor, agitation, restlessness, confusion and hallucinations may occur.

Severe toxicity:
Convulsions, hypotension and cardiac arrhythmias such as supraventricular or ventricular tachycardia or ventricular fibrillation may occur. Coma may develop in severe cases.

Metabolic features:
Metabolic features are common and include hypokalaemia (which may be severe), hyperglycaemia, hypophosphataemia, hypomagnesaemia and hypercalcaemia. Metabolic acidosis and respiratory alkalosis may be seen.

Complications:
Complications include pyrexia, rhabdomyolysis and renal failure.

 

Management:

1. Ensure clear airway and adequate ventilation.

2. Consider activated charcoal (50 g for adults; 10-15 g for children) if the patient has ingested more than 20 mg/kg. Since most theophylline products are slow release charcoal given more than 1 hour after ingestion may be of benefit. (See also point 13 for repeat dose charcoal.)

3. Observe for at least 4 hours after ingestion. With sustained release preparations observation should occur for at least 12 hours.

4. Monitor pulse, blood pressure and cardiac rhythm.

5. Measure urea and electrolytes and perform 12 lead ECG. In patients with features other than mild toxicity, measure arterial blood gases, calcium, magnesium and phosphate.

6. Theophylline concentration should be measured urgently in patients with features of significant toxicity. Theophylline concentration will be an indication of possible toxicity but clinical features are the best guide. (A low serum potassium may a useful surrogate marker of theophylline toxicity if theophylline concentration is not rapidly available).

In patients with severe poisoning or theophylline concentration > 60 mg/L (330 micromol/L) the theophylline concentration should be repeated every 2-4 hours, until peak concentrations have passed. This is particularly important if a slow release preparation has been taken.

7. Correct hypokalaemia (< 3.0 mmol/L) with intravenous potassium supplementation. Initial hypokalaemia, however, may not reflect true total body potassium depletion and severe rebound hyperkalaemia may occur during recovery. Repeated monitoring of electrolytes is suggested (1-2 hourly) in patients with severe poisoning.

Hypomagnesaemia may occur with severe hypokalaemia. Magnesium concentrations should be measured in such cases and corrected with parenteral magnesium as necessary.
Note that non selective beta blockers such as propranolol may help to correct hypokalaemia and this should be taken into consideration when calculating requirements for potassium supplementation.

8. Vomiting may be resistant to simple antiemetics. Ondansetron has been shown to be effective(Brown & Prentice, 1992; Roberts et al, 1993; Daly & Taylor 1993). Give 8 mg slowly intravenously in an adult (0.15 mg/kg in a child). Alternatively metoclopramide 10-30 mg in an adult.

9. Sinus tachycardia or supraventricular tachycardia with an adequate cardiac output is best left untreated. Beta-blockers may be given in severe cases but extreme caution should be used if the patient has asthma or COPD and in these cases a relatively beta-1 specific or short-acting beta-blocker such as metoprolol or esmolol may be considered (see below). Give propranolol 1 mg intravenously (25-50 microgrammes/kg in a child) repeated at 2 minute intervals as required to a maximum of 10 mg. Propranolol may also be effective in treating the metabolic complications (e.g. hypokalaemia) associated with theophylline overdose.

Alternatively metoprolol 5mg slowly intravenously repeated after 5 minutes to maximum of 10-15 mg in an adult or esmolol 50 microgrammes/kg slowly intravenously followed by an infusion of 50-200 microgrammes/kg/min in an adult ( 300-1000 microgrammes/kg in a child) may be given. These will not correct the metabolic disturbances in the same way as propranolol.

Patients with asthma or COPD who, after correction of hypokalaemia, have supraventricular tachycardias causing haemodynamic compromise should be treated with intravenous verapamil. Alternatively DC cardioversion should be considered.

10. Ventricular arrhythmias should be treated with DC cardioversion if causing haemodynamic compromise. Ventricular tachycardia has responded to intravenous magnesium in one patient with ischaemic heart disease. If there is no evidence of haemodynamic compromise give magnesium sulphate 8 mmol intravenously. Discuss with your local poisons service: in the UK NPIS 0870 600 6266, in Ireland NPIC (01) 809 2566.

11. Single brief convulsions do not require treatment. If frequent or prolonged control with intravenous diazepam (10-20 mg in adults; 0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). Give oxygen and correct acid base and metabolic disturbances as required.

Phenytoin (loading dose 15 mg/kg IV infusion in adults and children) may be considered if convulsions are unresponsive to the above measures, given slowly (over 20-30 minutes - see BNF) with BP and ECG monitoring. Animal studies suggest that phenytoin may not be as effective as an anticonvulsant as in other situations, and alternative anticonvulsants should be considered (eg barbiturates or intubation and ventilation with EEG monitoring).

12. If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation consider correction with 250 mL of 1.26% sodium bicarbonate i.v. in an adult and repeat as necessary (250 mL of 1.26% contains 37.5 mmol sodium bicarbonate). Alternatively 50 mL of 8.4% contains 50 mmol sodium bicarbonate but ideally should not be given by a peripheral venous line as it is irritant to veins and can cause skin necrosis in cases of extravasation.

Do not overcorrect metabolic acidosis since this may exacerbate hypokalaemia.

13. Repeat dose activated charcoal is the treatment of choice for severe poisoning and should be considered if the plasma theophylline concentration is >40 mg/L and, in patients for whom levels are not available, for patients with hypokalaemia and other features of significant poisoning. Give charcoal (50 g for adults; 10-15 g for children) by mouth or nasogastric tube provided the airway can be protected. This should be repeated every four hours.

14. Charcoal haemoperfusion should be considered if:

• Ileus/intestinal obstruction prevents administration of multiple dose activated charcoal
• Plasma theophylline concentration > 80 mg/L (acute) or > 60 mg/L (chronic). In infants under 6 months of age or the elderly charcoal haemoperfusion should be considered at theophylline concentrations > 40 mg/L. (Clinical features rather than theophylline concentration are the best guide for treatment.) Discuss with your local poisons service: in the UK NPIS 0870 600 6266, in Ireland NPIC (01) 809 2566. </UL> 15. Other measures as indicated by the patient's clinical condition.