THEOPHYLLINE OVERDOSE

Prof. A. Walubo

Department of Pharmacology

Case reportEmergency Dept.• A 22-yr-old F, • 6 hrs after ingestion of 20 g of S-R theophylline• Nausea, Vomiting and palpitations. • PMH: Not asthmatic & never used theophylline before• Lab: - K+ = 2.4 mmol/l;

- Theophylline s-conc.= 105 mg/L.

Admitted: ICU, • Intubated and mechanically ventilated • Admn charcoal by NG tube: 50g x 3 + magnesium sulfate.• Dev’ped => severe hypotension and convulsed:

- Rx: colloids, inotropes and diazepam, respectively.• 8 hrs: Theo-level had dropped to 48 mg/l.

=> haemoperfusion started, 6 hr later level was 24 mg/l; • The following 2 days, she made a full recovery.

Nephrol Dial Transplant (2005) 20: 2869

Pharmacological properties of theophylline

Mechanism• Inhibits PDE => increased cAMP.• Inhibits adenosine receptors, =>

tachycardia & CNS stimulation.• Increased catecholamines:

Adrenaline & noradrenaline

Neurological• Agitation, tremors, hypertonicity• Nausea, vomiting & hyperventilation• Seizures, coma

Cardiovascular• +ve inotropic & chronotropic action• SVT and ventricular arrhythmias• Hypotension, cardiac arrest

Respiratory• Smooth muscle relaxation• Improved ventilatory muscle power

Metabolic• Metabolic acidosis• Respiratory alkalosis• Hypokalaemia• Hypophosphataemia• Hypomagnesaemia• Hyperglycaemia

Gastrointestinal• Increased acid & pepsin secretion• Abdominal pain & GIT haemorrhage

Renal• Increased RBF• Increased GFR

Intensive Care Med (1990) 16:394-398

Clinical CategoriesMild Moderate Severe

Nausea V + toler. decont. V + not

toler.decont.

P < 120/min P < 140 P >140

SBP > 120 mmHg SBP > 100 mmHg SBP < 100 mmHg

No arrhythmia Atrial or V-ectopics SVT or V-Tachy.

Agitation or hyperreflexia Seizures

K < 3.0 mmol/L K < 3.0 mmol/L

Glu > 10 mmol/L Glu > 10 mmol/L

Rising Theo conc

NB: Potentially significant toxicity:- all chronic overmedication, - acute ingestions of > 10 mg/kg (8 mg/kg)- acute ingestions with mod-sev. s/s

Criteria for admission

• Theophylline > 50 mg/L in acute poisoning • Theophylline > 40 mg/L in chronic poisoning • Theophylline > 40 mg/L in pts < 6 m or > 60 yrs • Theophylline > 40 mg/L in pts with chronic illness

Indications for haemodialysis/perfusion

• Clinically severe toxicity. • Theophylline conc. > 150 mg/L. • Theophylline conc. > 100 mg/L in acute ingestion. • Theophylline conc. > 60 mg/L in chronic ingestion. • Failure of repeated dose charcoal therapy

NB: Local threshold concentrations can be chosen above which an unacceptable risk of life-threatening events exists even if the patient shows only moderate toxicity.

Management of severe theophylline poisoning

Emergency department• History and examination• ECG monitoring • Establish IV access, NS• Blood:- Theo level + Na, K,

ABG, Glu, Urea + Cr, & FBC

• Electrolyte therapy commence: - KCL 20 mmol/h

- MgSO4 10 mmol/h- KPO4 5 mmol/h

• Gastric lavage • Intragastric act. charcoal 50 g

Intensive care unit• Act charcoal 10 g hrly with 20%

mannitol or other carthatic.• IV-fluids: careful fluid balance• Repeat Theo: 4-6 hourly.• Sodium bicarbonate • Antiemetic: ondanstr. + ranitidine• Seizures – diazepam, then

thiopentone, intubation and positive pressure ventilation

• Serious arrhyth - ? propranolol• Severe toxicity: haemoperfusion or

hemodialysis.

Intensive Care Med (1990) 16:394-398

END