You are in: eMedicine Specialties >
Emergency Medicine > TOXICOLOGY
Toxicity, Theophylline
Article Last Updated: Jun 13, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Greg Hymel, MD, Consulting Staff, Department of Emergency Medicine, Saint Vincent Mercy Medical Center
Greg Hymel is a member of the following medical societies: American Academy of Emergency Medicine
Editors: Lance W Kreplick, MD, MMM, FAAEM, FACEP, Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC; John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital; Fred Harchelroad, MD, FACMT, Chair, Department of Emergency Medicine, Director of Medical Toxicology, Department of Emergency Medicine, Associate Professor, Allegheny General Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Author and Editor Disclosure
Synonyms and related keywords:
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
Background
Theophylline has indications for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Medication, diet, and underlying diseases can alter its narrow therapeutic window. Adverse effects can be evident at therapeutic serum levels.
Pathophysiology
Theophylline is absorbed rapidly after oral administration. Peak serum levels occur in 90-120 minutes. Fasting or large volumes of fluid enhance absorption. Enteric-coated and sustained-release tablets have a delayed absorption. Intravenous aminophylline reaches peak serum levels in 30 minutes.
Theophylline is 60% protein bound and has a distribution volume of 0.5 L/kg. Therapeutic serum levels range from 10-20 mcg/mL. Toxic levels are considered to be higher than 20 mcg/mL; however, adverse effects may be evident within the normal therapeutic range.
Theophylline is eliminated by the hepatic cytochrome P-450 system (85-90%) and by urinary excretion (10-15%). The half-life is 4-8 hours in young adults and is shorter in children and smokers. Diet, cardiac or liver disease, tobacco use, and medications affecting the cytochrome P-450 system can affect the half-life.
Theophylline affects the cardiovascular (CV), neurological, GI, and metabolic systems. Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, and acidosis commonly occur after an acute overdose.
Frequency
United States
The 2002 annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented 1030 exposures to theophylline, with 170 in children younger than 6 years and 757 in persons older than 19 years. Of the 585 theophylline exposures treated in health care facilities, 39 were reported to have major adverse outcomes and 8 fatalities were noted. The documented toxic exposures have decreased markedly over the past decade as the utilization of theophylline for the management of asthma has diminished.
Race
No scientific data have demonstrated that outcomes of theophylline toxicity are dependent on race.
Sex
No scientific data have demonstrated that outcomes of theophylline toxicity are dependent on sex.
History
- Symptomology correlates better with single acute ingestions than with chronic overexposures. Symptoms of acute theophylline overdose are as follows:
- Nausea
- Vomiting
- Abdominal pain
- Mild metabolic acidosis
- Hypokalemia
- Hypophosphatemia
- Hypomagnesemia
- Hyperglycemia
- Tachycardia
- Chronic theophylline overdose has minimal GI signs or symptoms.
- Seizures, hypotension, and significant dysrhythmias usually are not observed until serum levels approach 80 mcg/mL.
- Seizures are more common with acute overdose than with chronic overdose and may develop at lower serum concentrations (40-60 mcg/mL).
- Cardiac dysrhythmias are more common following an acute overdose than chronic overdose.
Physical
- Cardiovascular
- Sinus tachycardia (most common)
- Atrial fibrillation
- Atrial flutter
- Supraventricular tachycardia (SVT)
- Multifocal atrial tachycardia
- Ventricular tachycardia
- Hypotension (severe overdoses)
- Ventricular fibrillation
- Pulseless electrical activity (PEA)
- Cardiac arrest
- Neurological
- Tremors (most common)
- Restlessness
- Agitation
- Hallucinations
- Headaches
- Irritability
- Seizures (Persistent seizures may occur with serum levels >25 mcg/mL.)
- Gastrointestinal
- Nausea
- Vomiting
- Abdominal cramps
- Diarrhea
Causes
- Chronic toxicity
- Drug interactions (eg, ethanol [ETOH], cimetidine, oral contraceptives, allopurinol, macrolide, quinolone antibiotics)
- Liver disease
- Congestive heart failure
- Febrile viral upper respiratory illness
- Acute toxicity
- Accidental overdose
- Intentional overdose
Alcoholic Ketoacidosis
Anxiety
Asystole
Atrial Fibrillation
Atrial Flutter
Delirium Tremens
Diabetic Ketoacidosis
Epidural Hematoma
Gastroenteritis
Hypercalcemia
Hypophosphatemia
Multifocal Atrial Tachycardia
Shock, Septic
Status Epilepticus
Subarachnoid Hemorrhage
Subdural Hematoma
Toxicity, Carbon Monoxide
Toxicity, Cyanide
Toxicity, Disulfiram
Toxicity, Iron
Toxicity, Monoamine Oxidase Inhibitor
Toxicity, Toxaphene and Organochlorine
Ventricular Fibrillation
Ventricular Tachycardia
Lab Studies
- Obtain serum theophylline levels every 2-4 hours until the level falls.
- This is especially important following ingestion of extended-release formulations.
- Theophylline can form bezoars, resulting in ongoing absorption and toxicity despite general measures at GI decontamination.
- Order electrolytes and glucose tests to evaluate for the following:
- Hypokalemia
- Hyperglycemia
- Metabolic acidosis
- Hypercalcemia
- Hypophosphatemia
- Test for pregnancy in women of childbearing age.
Imaging Studies
- Obtain a CT scan of the brain if seizures occur.
Other Tests
Prehospital Care
- Establish airway, breathing, and circulation (ABCs).
- Intravenous benzodiazepines may abort seizures.
Emergency Department Care
Evaluate ABCs and, if indicated, perform endotracheal intubation.
- Vascular access for hemoperfusion may be required.
- Endotracheal intubation may be needed in patients who require high dose benzodiazepines or barbiturates to control seizures.
- Consider gastric lavage (unless contraindicated) if the patient has recently ( <1 h) ingested a significant amount or a sustained-release preparation or if bezoar formation is suspected. Endoscopic bezoar fragmentation and retrieval may be utilized if lavage is not efficacious.
- Administer activated charcoal.
- Multidose charcoal enhances elimination of theophylline.
- Administer the cathartic, sorbitol, with the activated charcoal one time.
- Phenobarbital prophylaxis may benefit patients at high risk for seizures. Similarly, benzodiazepines will increase the seizure threshold. 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
- Benzodiazepines (IV) and phenobarbital may be used to treat seizures.
- Phenobarbital has the added advantage of enhancing the hepatic metabolism of theophylline.
- Hypotension resistant to isotonic fluids (10-20 cc/kg) may require vasopressors with predominantly alpha-agonistic activity (eg, dopamine, norepinephrine).
- In patients with theophylline toxicity, beta-blockade with propranolol has been shown to successfully reverse peripheral beta receptor-mediated hypotension without apparent effect on concomitant tachycardia.
- However, always consider the risk of beta-adrenergic blockade to patients with pre-existent bronchospastic disease.
- Esmolol, a short-acting beta-blocker, has been used successfully for unstable SVT and related hypotension in theophylline overdose.
- 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 affect on beta2-mediated hypotension as less-selective agents (eg, propranolol), although it is less likely to induce bronchospasm than other beta-blockers.
- Consider hemoperfusion with the following:
- Theophylline concentrations exceed 40 mcg/mL (chronic ingestion)
- Presence of life-threatening toxicity
- Levels exceeding 90 mcg/mL in acute ingestions
- Hemodialysis is an alternative method of elimination enhancement but is considerably less effective than hemoperfusion.
- Current recommendations for treating patients with tachycardia, hypotension, anxiety, and vomiting from theophylline-overdose may include the following:
- Fluid bolus with isotonic fluid
- Metoclopramide to help control vomiting
- Propranolol to increase blood pressure
- Benzodiazepine to decrease anxiety, decrease risk of seizures, and help control vomiting
- Phenylephrine to further increase blood pressure
- Hemoperfusion guided by response to treatment, underlying medical problems, and theophylline level
Consultations
- Consult the regional poison control center or local medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.
- Consult a nephrologist if hemoperfusion is needed
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: GI decontaminant
Empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.
| Drug Name | Activated charcoal (Liqui-Char) |
|---|
| Description | Prevents absorption by adsorbing drug in intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. Theoretically, by constantly bathing the GI tract with charcoal, the intestinal lumen serves as a dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine. Supplied as an aqueous mixture or in combination with a cathartic (usually sorbitol 70%). |
|---|
| Adult Dose | 1 g/kg PO; may repeat in 2-4 h at one-half original dose |
|---|
| Pediatric Dose | 1 g/kg PO (typical 12.5-25 g)
<2 years: Use aqueous charcoal without cathartic |
|---|
| Contraindications | Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway and absent gag reflex |
|---|
| Interactions | May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; sherbet, milk, or ice cream decreases adsorption |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administration; after emesis with ipecac syrup, 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; protect airway in patients with depressed level of consciousness; if using multiple dose charcoal, monitor for presence of bowel sounds to minimize risk of charcoal ileus and vomiting with subsequent pulmonary aspiration |
|---|
Drug Category: Antiemetics
Persistent vomiting may interfere with decontamination.
| Drug Name | Ranitidine (Zantac) |
|---|
| Description | H2 antagonist that may be a useful adjunct in reducing emesis volume. |
|---|
| Adult Dose | 50 mg IV q8h |
|---|
| Pediatric Dose | 1 mg/kg IV q6-8h |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin |
|---|
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
|---|
| Precautions | Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment |
|---|
| Drug Name | Metoclopramide (Reglan) |
|---|
| Description | Works as antiemetic by blocking dopamine receptors in the chemoreceptor trigger zone of the CNS. Generally drug of choice because lower cost than ondansetron (Zofran). |
|---|
| Adult Dose | 10-20 mg IV; not to exceed 1 mg/kg; up to 3 mg/kg/d IV in divided doses prn |
|---|
| Pediatric Dose | <6 years: 0.1 mg/kg IV slowly over 1-2 min |
|---|
| Contraindications | Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction or perforation; history of seizure disorders |
|---|
| Interactions | May antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Caution in history of mental illness and Parkinson disease; adverse effects include drowsiness, hypotension, and acute dystonia, especially at high doses; may increase frequency of seizure in individuals with epilepsy |
|---|
| Drug Name | Droperidol (Inapsine) |
|---|
| Description | Neuroleptic agent that may reduce emesis by blocking dopamine stimulation of chemoreceptor trigger zone. |
|---|
| Adult Dose | 1.25 - 5 mg IV |
|---|
| Pediatric Dose | 0.05-0.25 mg/kg IV |
|---|
| Contraindications | Documented hypersensitivity |
|---|
| Interactions | May increase toxicity of CNS depressants; cabergoline and levodopa may potentiate antipsychotic effects |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Hypovolemic patients may experience hypotension; may decrease pulmonary arterial pressure; tardive dyskinesia in patients receiving droperidol is 40%; elderly persons may experience high rate of extrapyramidal reactions; life-threatening arrhythmias may occur; watch for QT prolongation |
|---|
| Drug Name | Prochlorperazine (Compazine) |
|---|
| Description | May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system.
In addition to antiemetic effects, has the advantage of augmenting hypoxic ventilatory response, acting as a respiratory stimulant at high altitude. |
|---|
| Adult Dose | 10 mg IV slowly; may repeat once; not to exceed 40 mg/d; 25 mg PR q12h |
|---|
| Pediatric Dose | <20 pounds: Not recommended
20-29 pounds: 2.5 mg PR bid
30-39 pounds: 2.5 mg PR tid
<12 years: 0.06 mg/lb IM |
|---|
| Contraindications | Documented hypersensitivity; bone marrow suppression, narrow-angle glaucoma, and severe liver or cardiac disease; parkinsonism; depression |
|---|
| Interactions | Coadministration with other CNS depressants or anticonvulsants may cause additive effects; may cause hypotension with epinephrine |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Drug-induced Parkinson syndrome or pseudoparkinsonism occurs quite frequently; akathisia is most common extrapyramidal reaction in elderly persons; lowers seizure threshold; caution with history of seizures; may cause hypotension, altered mental status, and NMS |
|---|
Drug Category: Benzodiazepines and other sedative agents
Used to terminate seizures and for seizure prophylaxis in high-risk patients. Helps to alleviate nausea and vomiting. Decreases tremors and anxiety induced by theophylline.
| Drug Name | Diazepam (Valium) |
|---|
| Description | Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing activity of GABA. |
|---|
| Adult Dose | 0.2 mg/kg IV at 2 mg/min; not to exceed 20 mg (as a single dose); may repeat, monitoring for respiratory depression |
|---|
| Pediatric Dose | 0.2-0.5 mg/kg IV
<5 years: Not to exceed 5 mg
> 5 years: Not to exceed 10 mg |
|---|
| Contraindications | Documented hypersensitivity; altered mental status; low BP or RR; narrow-angle glaucoma |
|---|
| Interactions | Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, cimetidine, barbiturates, alcohols, and MAOIs |
|---|
| Pregnancy | D - Unsafe in pregnancy
|
|---|
| Precautions | Caution with other CNS depressants, low albumin levels, hepatic disease (may increase toxicity), altered mental status, respiratory depression, or hypotension |
|---|
| Drug Name | Lorazepam (Ativan) |
|---|
| Description | Sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Monitoring blood pressure after administering dose is important. Adjust prn. |
|---|
| Adult Dose | 0.044 mg/kg (2-4 mg) IV; titrate to effect
Status epilepticus: 4 mg IV over 2-5 min; may repeat second dose in 10-15 min prn; not to exceed 8 mg |
|---|
| Pediatric Dose | Infants and children: 0.02-0.1 mg/kg IV slowly over 2-5 min; repeat prn in 10-15 min at 0.05 mg/kg; not to exceed 4 mg/dose
Adolescents: 0.07 mg/kg IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 4 mg/dose |
|---|
| Contraindications | Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma |
|---|
| Interactions | Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs |
|---|
| Pregnancy | D - Unsafe in pregnancy
|
|---|
| Precautions | Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses |
|---|
| Drug Name | Midazolam (Versed) |
|---|
| Description | Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access. |
|---|
| Adult Dose | 0.01-0.05 mg/kg (usually 0.5-4 mg; up to 10 mg) IV slowly over several min; may repeat q10-15min until adequate response achieved |
|---|
| Pediatric Dose | <32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), > 2 months and children: 0.15 mg/kg, followed by continuous infusion of 1 mcg/kg/min; titrate upward q5min until seizures controlled |
|---|
| Contraindications | Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent) |
|---|
| Interactions | Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together |
|---|
| Pregnancy | D - Unsafe in pregnancy
|
|---|
| Precautions | Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine) |
|---|
| Drug Name | Phenobarbital (Barbita, Luminal) |
|---|
| Description | Interferes with transmission of impulses from thalamus to cortex of brain. |
|---|
| Adult Dose | 10-20 mg/kg IV; not to exceed 50 mg/min |
|---|
| Pediatric Dose | 15-20 mg/kg IV; not to exceed 50 mg/min |
|---|
| Contraindications | Documented hypersensitivity; severe respiratory disease, marked impairment of liver function, and nephritic patients |
|---|
| Interactions | May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and fatality; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur |
|---|
| Pregnancy | D - Unsafe in pregnancy
|
|---|
| Precautions | In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema; monitor for hypotension, respiratory depression, and need for intubation |
|---|
Drug Category: Cardiovascular agents
Alpha-agonists are used to treat persistent hypotension not responding to fluid challenges. Beta-blockers are used for treating severe tachycardia with ischemia or severe hypotension.
| Drug Name | Phenylephrine (Neo-Synephrine) |
|---|
| Description | Strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles. Increases peripheral venous return. |
|---|
| Adult Dose | 100-180 mcg/min IV initial, then 40-60 mcg/min IV as tolerated |
|---|
| Pediatric Dose | 0.1 mg/kg (3 mg/m2) as a single IM/SC dose; repeat q1-2h; not to exceed 5 mg total |
|---|
| Contraindications | Documented hypersensitivity; anatomical narrow-angle; narrow-angle glaucoma; severe hypertension; tachycardia |
|---|
| 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- to 3-fold
Guanethidine may increase pressor response of direct-acting vasopressors, possibly resulting in severe hypertension |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Caution in elderly patients, hyperthyroidism, myocardial disease, bradycardia, partial heart block, or severe arteriosclerosis; in hypovolemia, use is not substitute for replacement of blood, fluids and electrolytes, and plasma (these should be restored promptly when loss occurs) |
|---|
| Drug Name | Esmolol (Brevibloc) |
|---|
| Description | Short-acting IV cardioselective beta-adrenergic blocker with no membrane depressant activity. Half-life of 8 min allows for titration to effect and quick discontinuation prn. |
|---|
| Adult Dose | Loading dose: 500 mcg/kg IV for 1 min
Maintenance infusion: 100 mcg/kg/min IV for 4 min; repeat if inadequate; if still inadequate, repeat loading dose, then increase maintenance dose by increments of 50 mcg/kg/min IV |
|---|
| Pediatric Dose | 300 mcg/kg/min IV with continuous heart rate and blood pressure monitoring to determine onset of beta-blockade (equal to >10% reductions); titrate upward in 50-100 mcg/kg/min increments IV q10min prn |
|---|
| Contraindications | Documented hypersensitivity; asthma; COPD; CHF; moderate-to-severe left ventricular dysfunction; hypotension <90 mm Hg; bradycardia <60/min, second- and third-degree AV block |
|---|
| 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 |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
|---|
| Precautions | Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely |
|---|
Further Inpatient Care
- 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 levels higher than 30 mcg/mL.
- Admit patients demonstrating cardiovascular or neurologic dysfunction to the critical care unit.
Further Outpatient Care
- Accidental overdose: For patients with therapeutic theophylline levels and minimal or no toxicity and acute ingestions less than 10 mg/kg, discharge and follow up within 24 hours.
- Intentional overdose: Consider discharge after psychiatric evaluation.
Patient Education
Medical/Legal Pitfalls
- Failure to aggressively treat a theophylline intoxicated patient in a manner to prevent risk of seizures
- Failure to initiate access to hemoperfusion in the severely intoxicated patient
- Failure to diagnose chronic theophylline overdose because of the vague signs and symptoms of anxiety and nausea, thereby inappropriately discharging them from the ED
- Brashear RE, Aronoff GR, Brier RA. Activated charcoal in theophylline intoxication. J Lab Clin Med. Sep 1985;106(3):242-5. [Medline].
- Charytan D, Jansen K. Severe metabolic complications from theophylline intoxication. Nephrology (Carlton). Oct 2003;8(5):239-242. [Medline].
- Cooling DS. Theophylline toxicity. J Emerg Med. Jul-Aug 1993;11(4):415-25. [Medline].
- Gaudreault P, Harwood-Nuss. Methylxanthines, Toxicology. In: Clinical Practice of Emergency Medicine. 4th ed. 2005:1649-1652.
- Henderson A, Wright DM, Pond SM. Management of theophylline overdose patients in the intensive care unit. Anaesth Intensive Care. Feb 1992;20(1):56-62. [Medline].
- Kallstrom TJ. Evidence-based asthma management. Respir Care. Jul 2004;49(7):783-92. [Medline].
- Kearney TE, Manoguerra AS, Curtis GP, Ziegler MG. Theophylline toxicity and the beta-adrenergic system. Ann Intern Med. Jun 1985;102(6):766-9. [Medline].
- Marshall H, Emerman CL, Tintinalli J. Theophylline, Toxicology and Pharmacology. In: Emergency Medicine, A Comprehensive Study Guide. 6th ed. 2004:1098-1101.
- Medical Economics Staff. Drugs. In: Physician's Desk Reference. Medical Economics Co;1997.
- Micromedex. Theophylline. In: Micromedex. 1974-2006:36.
- Seneff M, Scott J, Friedman B, Smith M. Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability. Ann Emerg Med. Jun 1990;19(6):671-3. [Medline].
Toxicity, Theophylline excerpt Article Last Updated: Jun 13, 2006
|
