Theophylline Toxicity Treatment & Management

Updated: Aug 31, 2020
  • Author: Christopher P Holstege, MD; Chief Editor: Stephen L Thornton, MD  more...
  • Print
Treatment

Emergency Department Care

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

Benzodiazepines and phenobarbital may be used to treat seizures. 

Hypotension resistant to isotonic fluids (20 mL/kg) may require vasopressors with predominantly alpha-agonistic 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. However, use caution using beta-blockers as the evidence for efficacy is limited and their is a risk of beta-adrenergic blockade to 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. [7] Exercise caution with beta-blocking agents because of their negative inotropic effects. Esmolol is a relatively selective beta1-receptor antagonist; thus, it may not have as much effect on beta2-mediated hypotension as 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 it being able to both enhance the clearance of the toxin and help correct metabolic derangements. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup recommends extracorporeal treatments if: [8]

  • Theophylline concentration >100 mg/L in acute exposures

  • Seizures are present

  • Life-threatening dysthymias are present

  • Shock is present

  • There is a rising serum theophylline concentration despite optimal therapy

  • There is clinical deterioration despite optimal therapy

The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup suggests extracorporeal treatments if:

  • Theophylline concentration > 60 mg/L in chronic exposures

  • The patient is less than 6 months or over 60 years old and the theophylline concentration >50 mg/L in chronic exposure

  • Gastrointestinal decontamination cannot be administered

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

Correct electrolyte abnormalities in patients with ECG changes (eg, QTc 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
  • 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 follow is recommended.  For asymptomatic patients with therapeutic levels following intentional overdose, consider discharge of after psychiatric evaluation.

Next:

Prevention

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. [5]

Previous