Theophylline Toxicity Treatment & Management

Evaluate ABCs (airway, breathing, circulation) and intervene as necessary. Endotracheal intubation may be needed in patients who require high-dose benzodiazepines or barbiturates to control seizures. Vascular access for hemoperfusion may be required.

Administer activated charcoal if the airway is patent and the patient is alert. Multidose activated charcoal (MDAC) enhances elimination of theophylline. It is important to control nausea and vomiting in order to perform MDAC treatment. It is also important that the patient is able to protect the airway, in order to prevent aspiration of activated charcoal. Administer sorbitol (as a cathartic) with the activated charcoal no more than one time.

Consider performing whole-bowel irrigation (WBI) in patients with exposure to sustained-release theophylline preparations. Administer polyethylene glycol electrolyte solution, as follows:

• Adults: 2 liters per hour until clear rectal effluent
• Children: 500 mL/h until clear rectal effluent

Theophylline-induced seizures tend to be resistant to treatment. Benzodiazepines (eg, lorazepam) are considered the first line of treatment. Historically, phenobarbital prophylaxis was used in patients at high risk for seizures. High-risk cases include the following:

• Acute overdose with theophylline levels higher than 80 mcg/mL
• Chronic toxicity with levels higher than 40 mcg/mL
• Patients older than 60 years or younger than 3 years with toxic levels

Hypotension resistant to isotonic fluids (20 mL/kg) may require vasopressors with predominantly alpha-agonist activity (eg, phenylephrine, norepinephrine). In patients with theophylline toxicity, beta-blockade with propranolol has been shown only in case reports to successfully reverse peripheral beta receptor-mediated hypotension without apparent effect on concomitant tachycardia. Exercise caution with beta-blockers, however, as the evidence for efficacy is limited and they pose a risk of beta-adrenergic blockade in patients with preexistent bronchospastic disease.

Esmolol, a short-acting beta-blocker, has been used successfully for unstable supraventricular tachycardia and related hypotension in theophylline overdose. ^[9] Esmolol is a relatively selective beta1-receptor antagonist, and thus may not have as much effect on beta2-mediated hypotension as do less-selective agents (eg, propranolol), although it is less likely to induce bronchospasm than other beta-blockers.

Extracorporeal treatments can be used in the treatment of theophylline poisoning, with hemodialysis being the preferred method due to its ability to both enhance the clearance of the toxin and help correct metabolic derangements. In cases of acute toxicity, the Extracorporeal Treatments in Poisoning (EXTRIP) workgroup recommends extracorporeal treatments for patients with any of the following: ^[10]

• Theophylline concentration > 100 mg/L
• Seizures
• Life-threatening dysrhythmias
• Shock
• A rising serum theophylline concentration despite optimal therapy
• Clinical deterioration despite optimal therapy

In cases of chronic toxicity, the EXTRIP workgroup suggests the following as indications for extracorporeal treatments ^[10] :

• Theophylline concentration > 60 mg/L
• Patient age less than 6 months or over 60 years and theophylline concentration > 50 mg/L
• Gastrointestinal decontamination cannot be performed

Hemodialysis can be stopped when there is apparent clinical improvement or theophylline concentration < 15 mg/L.

Correct electrolyte abnormalities in patients with electrocardiographic changes (eg, corrected QT interval prolongation) and/or ventricular dysrhythmias. Current recommendations for treating patients with tachycardia, hypotension, anxiety, and vomiting from theophylline overdose may include the following:

• Fluid bolus with isotonic fluid (20 mL/kg)
• Ondansetron to help control vomiting
• A benzodiazepine to decrease anxiety, decrease risk of seizures, and help control vomiting
• Phenylephrine or norepinephrine to increase blood pressure if fluid resuscitation fails.  

Because charcoal hemoperfusion is a complicated process that is not routinely used in healthcare facilities, most medical centers will perform hemodialysis. Hemodialysis in combination with MDAC often is sufficient for the treatment of severe theophylline toxicity.

Admit all patients with signs and symptoms of toxicity (acute or chronic), or observe them in the ED until their theophylline level decreases and their symptoms have resolved. Admit patients with theophylline levels higher than 30 mcg/mL. Admit patients demonstrating cardiovascular or neurologic dysfunction to the critical care unit.

Consult the regional poison control center or local medical toxicologist (certified through the American Board of Medical Toxicology) for additional information and patient care recommendations. Consult a nephrologist if hemoperfusion is needed.

For patients with therapeutic theophylline levels that are not rising, discharge with followup is recommended. For asymptomatic patients with therapeutic levels following intentional overdose, consider discharge after psychiatric evaluation.

Patients prescribed theophylline who have risk factors for reduced elimination or metabolism of the drug, such as congestive heart failure or liver disease, should be more closely monitored to avoid significant intoxication. ^[6]

Routine theophylline level monitoring is required annually for well-managed adults  and once every six months for children when given orally. Patients should receive education on theophylline toxicity and side effects as delays in diagnosis and treatment of toxicity can be life-threatening. ^[8]