Pediatric Theophylline Toxicity Treatment & Management

  • Author: Tracey H Reilly, MD; Chief Editor: Timothy E Corden, MD   more...
 
Updated: Nov 21, 2011
 

Medical Care

  • Initial stabilization: Initial treatment of theophylline poisoning involves assessment of the ABCs, cardiac monitoring, administration of isotonic fluids for rehydration, and determination of glucose level. Perform endotracheal intubation as indicated for airway protection and ventilatory assistance.
  • Treatment of cardiovascular effects: Observe for hypotensive effects. Administer isotonic fluids for hypotension. Refractory hypotension may require administration of a pure alpha-agonist vasopressor agent (eg, phenylephrine). Most patients tolerate theophylline-induced tachycardia without difficulty. Beta-blockers should be used with extreme caution, as mixed results following administration have been reported in the literature. Theophylline toxicity is refractory to adenosine. Ventricular dysrhythmias should be treated in the usual manner.
  • CNS hyperstimulation treatment: Patients who are preseizurogenic (ie, manifesting signs of hyperreflexia, clonus, and marked tremor) should be treated with either benzodiazepines or phenobarbital. If seizures develop, prompt therapy with benzodiazepines and phenobarbital should be initiated. Phenytoin may worsen theophylline-induced seizures and should be avoided.
  • Decontamination: Administer activated charcoal (1-2 g/kg). Consider whole-bowel irrigation for massive ingestion of sustained-release preparations. Multidose activated charcoal has been beneficial in the treatment of theophylline toxicity because it binds theophylline that diffuses through the small intestine ("gut dialysis"). Recurrent vomiting may be treated with metoclopramide or ondansetron.
  • Treatment of electrolyte disturbances: Treat hypokalemia cautiously in patients with acute ingestions. Hypokalemia is secondary to an intracellular shift, rather than total-body depletion. Potassium replacement may cause hyperkalemia as theophylline levels decrease. Most electrolyte disturbances are asymptomatic and do not require treatment.
  • Extracorporeal elimination: Hemodialysis is as efficacious as hemoperfusion and is the preferred method of extracorporeal elimination. Hemodialysis should be considered if the theophylline level is more than 100 mcg/mL in acute ingestions and more than 60 mcg/mL in chronic. In patients who develop seizures, refractory hypotension that is unresponsive to fluids, and unstable dysrhythmias, hemodialysis should be considered, regardless of the theophylline level. The molecular adsorbent recirculating system (MARS) has been cited in case reports as being efficacious in the removal of protein-bound drugs such as theophylline. However, the literature is quite limited in the use of MARS in the pediatric population, especially for the treatment of drug toxicity.[3]
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Consultations

  • Consult a toxicologist.
  • A nephrologist may be consulted in cases of severe toxicity requiring charcoal hemoperfusion or hemodialysis.
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Contributor Information and Disclosures
Author

Tracey H Reilly, MD  Attending Physician, Department of Emergency Medicine, United Health Services Hospitals

Tracey H Reilly, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, and American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Christopher P Holstege, MD  Associate Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Center; Associate Medical Toxicology Fellowship Director, Veterans Affairs Department of Health

Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, European Association of Poisons Centres and Clinical Toxicologists, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Chandra D Aubin, MD  Associate Residency Director, Division of Emergency Medicine, Assistant Professor, Washington University School of Medicine

Disclosure: Nothing to disclose.

Michael E Mullins, MD  Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine; Attending Physician, Emergency Department, Barnes-Jewish Hospital

Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Emergency Physicians

Disclosure: Johnson & Johnson stock ownership None; Savient Pharmaceuticals stock ownership None

Specialty Editor Board

Halim Hennes, MD, MS  Division Director, Pediatric Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director of Emergency Services, Children's Medical Center

Halim Hennes, MD, MS is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD  Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD  Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, et al. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). Dec 2007;45(8):815-917. [Medline].

  2. Adén U. Methylxanthines during pregnancy and early postnatal life. Handb Exp Pharmacol. 2011;373-89. [Medline].

  3. Novelli G, Rossi M, Morabito V, et al. Pediatric acute liver failure with molecular adsorbent recirculating system treatment. Transplant Proc. Jul-Aug 2008;40(6):1921-4. [Medline].

  4. Charytan D, Jansen K. Severe metabolic complications from theophylline intoxication. Nephrology (Carlton). Oct 2003;8(5):239-242. [Medline].

  5. de Pont AC. Extracorporeal treatment of intoxications. Curr Opin Crit Care. Dec 2007;13(6):668-73. [Medline].

  6. Holstege CP, Dobmeier S. Cardiovascular challenges in toxicology. Emerg Med Clin North Am. Nov 2005;23(4):1195-217. [Medline].

  7. Holstege CP, Hunter Y, Baer AB, et al. Massive caffeine overdose requiring vasopressin infusion and hemodialysis. J Toxicol Clin Toxicol. 2003;41(7):1003-7. [Medline].

  8. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. Apr 2005;12(2):78-85. [Medline].

  9. Minton NA, Henry JA. Acute and chronic human toxicity of theophylline. Hum Exp Toxicol. Jun 1996;15(6):471-81. [Medline].

  10. Minton NA, Henry JA. Treatment of theophylline overdose. Am J Emerg Med. Oct 1996;14(6):606-12. [Medline].

  11. Rutten J, van den Berg B, van Gelder T, van Saase J. Severe theophylline intoxication: a delay in charcoal haemoperfusion solved by oral activated charcoal. Nephrol Dial Transplant. Dec 2005;20(12):2868-9. [Medline].

  12. Shannon MW. Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication. Acad Emerg Med. Jul 1997;4(7):674-8. [Medline].

  13. Stork CM, Howland MA, Goldfrank LR. Concepts and controversies of bronchodilator overdose. Emerg Med Clin North Am. May 1994;12(2):415-36. [Medline].

  14. Watson WA, Litovitz TL, Rodgers GC, et al. 2004 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2005;23(5):589-666. [Medline].

 
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