eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Theophylline

Tracey H Reilly, MD, Attending Physician, Department of Emergency Medicine, United Health Services Hospitals
Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health; Chandra D Aubin, MD, Associate Residency Director, Division of Emergency Medicine, Assistant Professor, Washington University School of Medicine; Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine

Updated: Dec 9, 2008

Introduction

Background

The frequency of theophylline overdose has greatly decreased as the use of theophylline for the treatment of asthma and chronic obstructive pulmonary disease (COPD) has declined because of its narrow therapeutic window and the effectiveness of inhaled beta-agonists. The occurrence of adverse effects with theophylline, even at levels in the therapeutic range, and the severity of its effects in acute and chronic overdose are notable; however, theophylline continues to be prescribed for some patients.

Pathophysiology

Theophylline is a methylxanthine derivative that works by inhibiting phosphodiesterase and potentiating intracellular levels of cyclic adenosine monophosphate (cAMP). It is also an antagonist at adenosine receptors in the bronchial smooth muscle, peripheral vasculature, CNS, and myocardium. Peak serum levels occur 90-120 minutes after oral administration, and sustained-release preparations are common; these preparations cause delayed absorption and potential bezoar formation.

Theophylline is 56% protein bound and has a volume of distribution of 0.5 L/kg. Approximately 90% of it is metabolized by the CYP1A2 isozyme of the hepatic cytochrome P450 system to form inactive substances, and 10% is excreted unchanged in the urine. The elimination half-life is significantly longer in neonates than in children and adolescents and is increased in patients with viral illness, congestive heart failure, and hepatic disease. Theophylline metabolism is inhibited by drugs that affect the cytochrome P450 system such as cimetidine, macrolides, and fluoroquinolones. Drugs such as phenytoin, barbiturates, carbamazepine, and tobacco can increase the metabolism of theophylline and lead to toxicity when they are discontinued.

Theophylline affects various body systems, as follows:

• Cardiovascular system: Theophylline stimulates beta1-receptors and can cause atrial tachydysrhythmias such as sinus and supraventricular tachycardia, even at therapeutic levels. Higher levels can also cause atrial fibrillation, multifocal atrial tachycardia in patients with COPD, and, occasionally, ventricular tachycardia or fibrillation. Hypotension may occur in severe overdoses secondary to beta2-receptor–stimulated vasodilatation. It may be refractory to fluids and conventional vasopressors.
• CNS: Neurologic adverse effects, including tremor, restlessness, and agitation, can also occur at therapeutic levels. Seizure is the most severe neurologic effect, occurring at levels higher than 90 mcg/mL in acute overdose, higher than 30 mcg/mL in acute-on-chronic ingestion, and as low as 20 mcg/mL in chronic toxicity.
• GI system: Nausea and vomiting are common in acute overdose. Abdominal pain and diarrhea can occur, and drug bezoars may occur with ingestion of sustained-release products.
• Metabolic system: Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, hypomagnesemia, and metabolic acidosis can occur secondary to beta-adrenergic stimulation.

Frequency

United States

In 2006, the American Association of Poison Control Centers (AAPCC) reported 413 exposures to theophylline or aminophylline; 73 of those exposures were in children younger than 19 years.¹ The incidence of theophylline toxicity has greatly decreased over the past decade. This decline in the prescription of theophylline is secondary to the safety and efficacy of the inhaled beta2-agonists in the treatment of asthma and COPD.

International

No current statistics on the international use of theophylline are available, although the drug continues to be available. It is potentially available without prescription in some countries.

Mortality/Morbidity

The most significant morbidity and mortality of theophylline toxicity in acute overdose are secondary to the cardiovascular and CNS effects. Life-threatening tachydysrhythmias and hypotension, as well as refractory seizures, can occur.

Age

Although theophylline toxicity can occur in people of any age, it is more severe in neonates than in children and adolescents.

Clinical

History

• Acute theophylline overdose causes nausea and vomiting, abdominal pain, tachycardia, mild metabolic acidosis, hypokalemia, hypercalcemia, hypophosphatemia, hypomagnesemia, and hyperglycemia. Severe symptoms such as seizures, dysrhythmias, and hypotension usually do not occur with acute overdose until levels are 80-100 mcg/mL.
• Chronic intoxication often causes milder GI symptoms and does not cause electrolyte shifts or hypotension, as observed in acute overdose. However, significant dysrhythmias and seizures are common with lower levels of the drug in chronic intoxication and in acute-on-chronic overdose.
• Theophylline toxicity should be considered in patients with new-onset seizures or status epilepticus with an opportunity for exposure.

Physical

• Cardiovascular findings: Sinus tachycardia is the most common finding. Supraventricular tachycardia, atrial fibrillation, atrial flutter, multifocal atrial tachycardia, and, less commonly, ventricular dysrhythmias can occur. Hypotension commonly occurs in acute overdose.
• Neurologic findings: Tremors, restlessness, agitation, and seizures are common.
• GI findings: Nausea, vomiting, abdominal pain, and diarrhea can occur.

Causes

• Acute toxicity occurs with accidental or intentional overdose.
• Chronic toxicity is caused by excessive daily dosing or interactions of drugs such as macrolide or quinolone antibiotics, allopurinol, oral contraceptives, and cimetidine, which lower the metabolism of theophylline and thereby increase its serum concentrations. Anticonvulsant medications such as phenytoin, phenobarbital, and carbamazepine enhance theophylline metabolism and increase levels of theophylline when these drugs are discontinued.

Differential Diagnoses

Workup

Laboratory Studies

• Serum theophylline levels should be determined every 2 hours until levels decline and every 4 hours until 2 successive findings are below therapeutic levels.
• Check the basic metabolic panel (BMP) for metabolic acidosis and hyperglycemia and determine calcium, phosphorus, and magnesium levels. In the most severe cases, all organ systems may be affected and appropriate laboratory levels, such as creatine kinase and urine myoglobin levels, should be obtained to determine if rhabdomyolysis has occurred.

Imaging Studies

• A kidneys, ureters, and bladder (KUB) radiograph may reveal radiopacities from undissolved sustained-release tablets or pharmacobezoars. Bead-filled capsules may appear as radiolucencies.
• Nonenhanced head CT scans may be obtained if seizures occur.

Other Tests

• Electrocardiography and ECG monitoring may be needed to observe for the development of atrial and ventricular tachydysrhythmias.

Procedures

• Endotracheal intubation should be performed as indicated for airway protection in patients with an altered mental status and vomiting, status epilepticus, or hemodynamic instability.
• Nasogastric tube placement may be required to deliver multidose activated charcoal.
• Hemodialysis may be required in cases of severe toxicity.

Treatment

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.²

Consultations

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

Medication

Antiemetics

These agents may be used to control vomiting. Phenothiazine antiemetics should be avoided to prevent potentiation of theophylline toxicity.

Metoclopramide (Reglan)

Dopamine antagonist that stimulates acetylcholine release in myenteric plexus. Centrally acts on chemoreceptor triggers in floor of fourth ventricle, which provides important antiemetic activity.

Dosing

Adult

0.4-1 mg/kg IV q6-8h; not to exceed 10-20 mg/dose

Pediatric

<6 years: 0.1 mg/kg IV infused over 1-2 min
6-14 years: 2.5-5 mg IV infused over 1-2 min
>14 years: Administer as in adults

Interactions

Anticholinergic drugs may antagonize effects; opiate analgesics may increase toxicity in CNS

Contraindications

Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction, or perforation; history of seizure disorders

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in history of mental illness and Parkinson disease; monitor for EPS

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin peripherally and centrally. Prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and complete-body radiation therapy.

Dosing

Adult

0.15 mg/kg/dose IV prn; not to exceed 32 mg/d

Pediatric

>3 years: Administer as in adults

Interactions

Cytochrome P450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) may change half-life and clearance; dose adjustment usually not required

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

For prevention of nausea and vomiting, not for rescue of nausea and vomiting

Drug absorption reducers

Activated charcoal is used to decrease drug absorption and may be all that is required in mild-to-moderate toxicity. It is not absorbed and is excreted entirely through the GI tract.

Activated charcoal (Actidose-Aqua, Liqui-Char)

Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal absorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water. For maximum effect, administer within 30 min after poison ingestion.

Dosing

Adult

1 g/kg (50-100 g) PO; usually given with sorbitol the first dose only

Pediatric

1-2 g/kg PO; avoid cathartic (ie, sorbitol) in patients <2 y

Interactions

May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases absorbent properties)

Contraindications

Documented hypersensitivity; poisoning or overdose of mineral acids and alkalis; unprotected airway with absent gag reflex

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Assess bowel sounds prior to administration to minimize occurrence of charcoal ileus; not effective in ethanol, methanol, and iron salt poisoning; induce emesis before administration; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black; repeated doses of cathartics can cause severe volume loss and electrolyte disturbance, especially in children

Whole bowel irrigation agents

Polyethylene glycol is used to increase GI transit time, decreasing absorption of theophylline. It may be used in older children or adults who have ingested significant amounts of products with delayed absorption. It is not absorbed and is entirely excreted through the GI tract.

Polyethylene glycol (GoLYTELY, NuLytely, Colovage, Colyte)

Laxative with strong electrolyte and osmotic effects that has cathartic actions in GI tract.

Dosing

Adult

2 L/h NG

Pediatric

1-2 mL/kg/h PO/NG

Interactions

Reduces effectiveness and absorption of oral medications

Contraindications

Documented hypersensitivity; colitis; megacolon; bowel perforation; gastric retention; GI obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in ulcerative colitis and hot loop polypectomy

Benzodiazepines

These agents may be needed to control agitation and seizures.

Diazepam (Valium)

Depresses all levels of CNS (eg, limbic system, reticular formation), possibly by increasing activity of GABA. Individualize dose and increase doses cautiously to avoid adverse effects.

Dosing

Adult

0.2 mg/kg IV at 2 mg/min, not to exceed 20 mg; may titrate dose according to adverse effects (ie, monitor for respiratory depression)

Pediatric

<5 years: 0.2-0.5 mg/kg IV, not to exceed 5 mg/dose
>5 years: 0.2-0.5 mg/kg IV, not to exceed 10 mg/dose
Titrate dose according to adverse effects (ie, monitor for respiratory depression); administer IV by slow injection, not to exceed 5 mg/min

Interactions

CNS toxicity of benzodiazepines increases with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; altered mental status; hypotension; respiratory depression

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution with other CNS depressants, low albumin levels, and hepatic disease (may increase toxicity)

Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life. May depress all levels of CNS, including limbic system and reticular formation, by increasing action of GABA, a major inhibitory neurotransmitter in the brain. Excellent when sedation longer than 24 hours is needed.

Dosing

Adult

0.04 mg/kg (2-4 mg) IV; titrate to effect
Status epilepticus: 4 mg IV infused slowly over 2-5 min; may repeat in 10-15 min prn; not to exceed 8 mg/12 h

Pediatric

0.05 mg/kg IV (range 0.02-0.1 mg/kg)
Status epilepticus:
Neonates: 0.05 mg/kg IV infused slowly over 2-5 min; may repeat in 10-15 min prn
Infants and children: 0.1 mg/kg IV infused slowly over 2-5 min; second dose of 0.05 mg/kg after 10-15 min prn
Adolescents: Administer as in adults; not to exceed 4 mg/12 h

Interactions

CNS toxicity of benzodiazepines increases with concurrent administration of alcohol, phenothiazines, barbiturates, and MAOIs

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, altered mental status, respiratory depression, hypotension, organic brain syndrome, and Parkinson disease

Alpha agonists

These agents are used to treat hypotension refractory to fluid challenge.

Phenylephrine (Neo-Synephrine)

Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body. Increases peripheral venous return.

Dosing

Adult

100-180 mcg/min IV initially; decrease to 40-60 mcg/min as tolerated

Pediatric

0.1 mg/kg (3 mg/m²) IM/SC; repeat q1-2h; not to exceed 5 mg/dose
0.1-0.5 mcg/kg/min IV infusion; titrate to desired effect

Interactions

Bretylium may potentiate action of vasopressors on adrenergic receptors, possibly resulting in arrhythmias; MAOIs may significantly enhance adrenergic effects, and pressor response may be increased 2-fold to 3-fold; guanethidine may increase pressor response of direct-acting vasopressors, possibly resulting in severe hypertension

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; severe hypertension; tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients and those with asthma, thyroid disease, BPH, hyperthyroidism, myocardial disease, bradycardia, partial heart block, or severe arteriosclerosis; in hypovolemia, use is not a substitute for replacement of blood, fluids and electrolytes, and plasma (promptly restore with loss); dilute IV and administer via large vein; extravasation precautions required

Beta-adrenergic blocking agents

These agents are used to treat severe tachycardia with ischemia or severe hypertension. Short-acting agents should be used because of the potential for significant hypotension in theophylline toxicity.

Esmolol (Brevibloc)

Excellent in patients at risk for complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Dosing

Adult

500 mcg/kg IV bolus initially, followed by 50 mcg/kg/min IV infusion; may increase by increments of 50 mcg/kg/min q4-5min prn; not to exceed 200 mcg/kg/min

Pediatric

300 mcg/kg/min IV infusion with continuous heart rate and BP monitoring to determine onset of beta-blockade (ie, >10% reduction); titrate upward by 50-100 mcg/kg/min q10min to desired effect

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole, calcium-channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents

Contraindications

Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in atrial fibrillation and bronchospasm; use infusion pump; beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen with abrupt withdrawal (withdraw drug slowly and monitor patient closely)

Follow-up

Further Inpatient Care

• Admit all patients with signs or symptoms of theophylline toxicity.
• Admit patients with serial unchanged or increasing theophylline levels of more than 30 mcg/mL in acute or acute-on-chronic ingestions of sustained-release preparations.
• Admit patients with cardiovascular or neurologic symptoms to the ICU, with airway management, monitoring, and supportive care as indicated.
• Patients with significant cardiovascular or neurologic symptoms should receive hemodialysis. Multidose activated charcoal should be used for patients with less severe toxicity.

Further Outpatient Care

• Patients with 2 consecutive decreasing theophylline levels of less than 30 mcg/mL, determined at least 2 hours apart, who are asymptomatic and who have no comorbid conditions may be considered for discharge.

Inpatient & Outpatient Medications

• Inpatient medications have been discussed previously (see Medication).
• Patients with 2 consecutive decreasing levels of less than 30 mcg/mL who are asymptomatic may be discharged, and further doses of theophylline should not be resumed until levels are within the therapeutic range (10-20 mcg/mL).
• No outpatient medications are required for the treatment of theophylline toxicity.

Transfer

• Patients with dysrhythmias, hemodynamic instability, or severe agitation, altered mental status, or seizures after ingestions of significant amounts of theophylline should be transferred to the ICU. These patients should also be transferred to facilities that can provide hemodialysis.

Deterrence/Prevention

• Drug levels should be periodically monitored in patients who are being treated with theophylline.
• Particular attention should be paid to potential drug interactions.
• Macrolide and quinolone antibiotics should be avoided. If they are administered, theophylline levels should be carefully monitored.
• Patients should be counseled about the potential for serious toxicity in acute and chronic overdose and about the potential for drug interactions.

Prognosis

• The prognosis of patients with theophylline toxicity depends on the amount and severity of the ingestion. Significant ingestions increase the risk of death from dysrhythmias, refractory hypotension, or status epilepticus.
• Hypoxic brain injury is a risk in patients with status epilepticus, prolonged hypotension, or significant aspiration causing hypoxia.

Patient Education

• Patients should be advised of the potential for serious toxicity in acute and chronic overdose and of the potential for serious drug interactions.
• Patients should be advised that current drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD), such as inhaled beta-agonists and inhaled steroids, offer better therapeutic effects without the risk of significant toxicity associated with theophylline.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

Miscellaneous

Medicolegal Pitfalls

• Because inhaled beta-agonists and steroids are effective in the treatment of asthma and chronic obstructive pulmonary disease (COPD) and because they do not have the risk of serious or fatal toxicity, a potential liability is associated with the continued prescription of theophylline for patients with these conditions.

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. 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].

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

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

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

6. 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].

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

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

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

10. 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].

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

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

13. 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].

Keywords

theophylline toxicity, theophylline overdose, acute theophylline overdose, chronic theophylline intoxication, methylxanthine, asthma treatment, chronic obstructive pulmonary disease treatment, COPD treatment, theophylline adverse affects, theophylline prescription, methylxanthine derivative, 1, 3-dimethylxanthine, smooth muscle relaxant, diuretic, cardiac stimulant, vasodilator, angina pectoris treatment, peripheral vascular disease treatment, bronchial asthma treatment, hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, hypomagnesemia, and metabolic acidosis,  atrial fibrillation, atrial flutter, multifocal atrial tachycardia

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; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept 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 Association for the Advancement of Science, American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, 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, Department of Emergency Medicine, Washington University School of Medicine
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

Medical Editor

Halim Hennes, MD, MS, Pediatric Emergency Medicine Research Director, Professor, Departments of Pediatrics and Emergency Medicine, Medical College of Wisconsin
Halim Hennes, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Merck Salary Employment

CME Editor

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.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)