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

Toxicity, Carbamazepine

Muhammad Waseem, MD, Associate Professor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University; Consulting Staff, Department of Pediatrics, Bronx Lebanon Hospital; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center
Joel R Gernsheimer, MD, FACEP, Visiting Associate Professor, Department of Emergency Medicine, Attending Physician and Director of Geriatric Emergency Medicine, State University of New York Downstate Medical Center; Nicholas D Caputo, MD, House Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center/Weill Cornell Medical College

Updated: Oct 27, 2009

Introduction

Background

Carbamazepine (Tegretol) has been used for the treatment of trigeminal neuralgias since 1960. Since carbamazepine received approval for use as an antiepileptic agent in the United States in 1974, it became widely used for the management of partial or tonic-clonic epilepsy. Carbamazepine is also used as a treatment for patients with manic-depressive illness, postherpetic neuralgia, and phantom limb pain. Some of the available dosage forms for carbamazepine include 100-mg and 200-mg oral tablets and a 100-mg/5-mL oral suspension.

The therapeutic plasma concentration is 4-12 mg/L. A peak plasma level is achieved in 6-24 hours. Controlled-release formulation could result in peak levels as late as 4 days after administration.¹ The volume of distribution is 1-2 L/kg. Carbamazepine is approximately 75-80% protein bound, and approximately 2-3% is excreted unchanged in the urine. Carbamazepine is oxidized by hepatic microsomal enzymes to produce its active metabolite, carbamazepine 10,11-epoxide. The serum concentration of the epoxide metabolite is approximately 20% in children and 10-15% in adults.

Autoinduction of microsomal enzyme results in a shorter carbamazepine half-life (10-20 h) in patients who use the drug long-term compared with those with a short-term exposure (31-35 h). The autoinduction process takes about 4 weeks.

In terms of drug interactions, carbamazepine induces the metabolism of other anticonvulsant drugs such as phenytoin, clonazepam, primidone, valproic acid, and ethosuximide. This may lead to subtherapeutic levels of these drugs, especially phenytoin.

Inhibitors of hepatic microsomal enzymes, such as erythromycin, clarithromycin, cimetidine, and propoxyphene, increase carbamazepine levels and may cause toxicity. Carbamazepine may increase the toxicity of adenosine and may increase the risk of heart block. Lower initial doses of adenosine should be used in patients who are taking carbamazepine.

Chemical structure of carbamazepine.

Pathophysiology

Carbamazepine is a complex drug that has both anticonvulsant properties in therapeutic doses and a proconvulsant property in overdose situations with supratherapeutic serum levels. Carbamazepine is chemically and stereospatially related to the tricyclic antidepressant (TCA) imipramine; it is spatially similar to phenytoin. The therapeutic anticonvulsant mechanism of carbamazepine is similar to phenytoin and is believed to be primarily related to the blockade of presynaptic voltage-gated sodium channels.

Blockage of sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. It also inhibits N -methyl-D-aspartate (NMDA) receptors and CNS adenosine receptors. Carbamazepine also has powerful anticholinergic properties through inhibition of the muscarinic and nicotinic acetylcholine receptors. The seizures that occur with carbamazepine toxicity are largely secondary to a central anticholinergic syndrome. The coma and respiratory depression associated with overdose may be related to sodium channel suppression of neurotransmission. Carbamazepine causes antagonism at the adenosine subtype A1 receptor and agonism at the adenosine subtype A2 receptor. In lower therapeutic doses, this may be partially responsible for the anticonvulsant effect, whereas, in overdose situations, it may increase sedation or precipitate coma.

Cardiac arrhythmias due to carbamazepine are related to its sodium channel and anticholinergic effects. In therapeutic doses, the cardiovascular sodium channels are only minimally affected, and carbamazepine does not appear to be proarrhythmic. However, in overdose situations, carbamazepine produces sodium channel blockade effects similar to those of TCAs.

Frequency

United States

Because of widespread use of carbamazepine in patients with pediatric epilepsy, the incidence of carbamazepine poisoning is increasing in all age groups. In 1997, the American Association of Poison Control Centers recorded 7151 cases of carbamazepine intoxication.¹

Mortality/Morbidity

In 2007, among 4,255 exposures to carbamazepine, 78 patients had a major toxicity, and 1 death was reported.¹ Complications of severe poisoning include coma, respiratory depression, seizures, hypotension, and GI hypomotility. Cardiac toxicity is uncommon in children, especially in those who have a structurally normal heart.

Sex

No specific sex predilection has been noted.

Age

Of the 2230 cases of carbamazepine toxicity reported by the American Association of Poison Control Centers in 2004, 660 were reported among children younger than 6 years, 380 were reported among children aged 6-19 years, and 1,190 were reported in individuals older than 19 years.¹ Most pediatric patients are younger than 6 years.

Clinical

History

• Ingestion history
  • Unintentional ingestions of carbamazepine are common in children younger than 6 years; suicidal ingestions typically occur in adolescents.
  • Other causes of carbamazepine poisoning include iatrogenic overdose; dosage errors; and interactions with drugs such as erythromycin, cimetidine, isoniazid, and propoxyphene. All these drugs increase the levels of carbamazepine by competitively inhibiting its metabolism.
  • The medication source is usually the patient or another family member who is taking carbamazepine for seizure control or the treatment of other illness.
  • An important cause of toxicity in children who are using the suspension is failure to adequately shake the bottle. Because the drug settles to the bottom of the bottle, if the full bottle is not shaken, the patient actually receives a low dose of the drug, which may lead to subtherapeutic levels and seizures. However, if the child is subsequently given doses of the drug from the bottom of the unshaken bottle, the patient may develop toxicity because the active drug has been concentrated there.
• Symptom history
  • Symptoms usually appear within 6 hours of ingestion but may be delayed as long as 24 hours after the ingestion. Case reports indicate the possibility of delayed absorption, which causes levels to peak as late as 72 hours.
  • Mild toxic ingestions cause vomiting, drowsiness, ataxia, slurred speech, nystagmus, dystonic reactions, and hallucinations.
  • Severe intoxications may produce coma, seizures, respiratory depression, and hypotension.

Physical

Carbamazepine toxicity should be considered in any child who presents with seizures, apnea, or an unexplained change in mental status, particularly when the child has access to the drug. The serum concentration may not always be directly correlated with the clinical picture. The severity of toxicity is assessed on the basis of the clinical status and not the serum carbamazepine concentration.

• Vital signs
  • Hypothermia may occur after an acute overdose and may last as long as 10 hours.
  • Hyperthermia may occur as part of a neuroleptic malignant syndrome.
• Neurologic effects
  • Common neurologic effects include ataxia, slurred speech, nystagmus, dystonia and other extrapyramidal movements, and various degrees of CNS depression. Seizures are common in children with an underlying epileptic disorder.
  • In severe cases, coma and status epilepticus may occur.
  • Neuroleptic malignant syndrome and transient ophthalmoplegia are also associated with carbamazepine overdose.
  • Syndrome of inappropriate antidiuretic hormone secretion has also been reported.
• Respiratory effects
  • Respiratory depression or apnea that requires mechanical ventilation may be observed within first 24 hours of the patient's presentation.
  • Pulmonary edema or aspiration pneumonia may occur.
  • Fulminant interstitial pneumonitis may also be noted.²
• Cardiovascular effects
  • Cardiovascular effects are rarely observed in children.
  • Hypotension, bradycardia, and conduction disorders may occur in those with an abnormal myocardium or a preexisting conduction defect.
• GI and hepatic effects
  • Anticholinergic effects include delayed gastric emptying and decreased intestinal motility.
  • With acute carbamazepine toxicity, chemical pancreatitis without accompanying pain or abnormalities may be present.
  • Hepatitis and, rarely, hepatic failure may occur. This is usually due to an idiosyncratic reaction rather than an overdose.
• Hematologic effects
  • Neutropenia, agranulocytosis, thrombocytopenia, and aplastic anemia may occur with therapeutic doses or chronic intoxication but not after an acute overdose. Carbamazepine has also been reported to have induced immunoglobulin deficiency in some cases in therapeutic doses;³ however, this has not been reported in acute intoxication.
  • Thrombocytopenia or aplastic anemia can result in bleeding; however, this effect is rarely seen with acute poisoning.
• Dermatologic effects (Dermatologic effects are due to idiosyncratic reactions rather than to an overdose of carbamazepine.)
  • Toxic epidermal necrolysis⁴
  • Hypersensitivity syndrome⁵
  • Stevens-Johnson syndrome⁶
  • Tendon sheath abscess⁷
• Fatalities: Death may result from apnea, status epilepticus,⁸ aspiration pneumonitis, severe hepatitis, or aplastic anemia.

Differential Diagnoses

Other Problems to Be Considered

• Acute change in mental status: In patients who have a history of seizures while taking carbamazepine, the postictal state (after an unwitnessed seizure) and an acute mental status change due to carbamazepine overdose are difficult to differentiate. Always consider other causes of coma in a child with no prior history of illness. Other causes include trauma, suspected child abuse, infections, CNS tumors, hypoglycemia, and other intoxications.
• Arrhythmias: Although arrhythmias are uncommon in pediatric patients, they may occur in children with underlying cardiac disease and with very large overdoses. Other causes of arrhythmias should be assessed, including electrolyte abnormalities, hypoxia, and overdoses with other drugs known to cause arrhythmias (eg, Dilantin, digoxin, cocaine, tricyclic antidepressants [TCAs]).
• Seizures: In patients taking long-term carbamazepine therapy for epilepsy, identifying the cause of the current seizure is important. A seizure could be due to subtherapeutic drug levels, breakthrough seizures with therapeutic drug levels, or carbamazepine toxicity. Other causes must also be considered; these include trauma, hypoglycemia, electrolyte disturbances, brain tumors, CNS infections, or new-onset epilepsy.

Workup

Laboratory Studies

• The workup in a patient with suspected carbamazepine poisoning should include appropriate comprehensive serum and urine drug screening with analysis of the following:
  • Alcohol level, if alcohol toxicity is suspected, particularly in adolescents
  • Serum electrolyte levels, including glucose, calcium, magnesium, phosphate, serum bicarbonate, BUN, and serum creatinine levels
• Liver function tests should also be performed because elevated liver enzyme levels, hepatitis, and hyperammonemia may be noted with chronic toxicity.
• Serum drug testing should be based on the history of ingestion and/or the patient’s toxidrome.
  • A serum and urine drug screen may not detect carbamazepine; therefore, the serum carbamazepine level should also be determined if the patient has access to carbamazepine. Structural similarity between carbamazepine and tricyclic antidepressants (TCAs) may cause false-positive results with immunoassay for TCAs.
  • Because carbamazepine absorption varies, the serum concentration may not peak for as long as 24-72 hours. With controlled-release formulation, levels may continue to rise until 4 days postingestion.
  • Initial serum levels of more than 35 mg/L (127 µmol/L) suggest serious toxicity. However, lower initial serum levels do not necessarily indicate a benign course and the patient still needs to be closely monitored for signs and symptoms of significant toxicity.
  • The serum concentration may not always directly correlate with the clinical picture. The severity of toxicity is assessed on the basis of the clinical status and not only the serum carbamazepine concentration.
• Toxicity may result from carbamazepine itself or its active epoxide metabolite. However, measuring epoxide levels along with the carbamazepine level provides no additional advantage.
• The CBC count with a differential and platelet count should be obtained.

Imaging Studies

• With acute carbamazepine toxicity, ultrasonography may reveal chemical pancreatitis without accompanying pain or other signs and symptoms.

Other Tests

• Perform a 12-lead ECG in patients with suspected poisoning.
• Continuous EEG recordings in a case with unconsciousness, absent brainstem reflexes, and stimulus-sensitive multifocal myoclonus revealed a burst-suppression pattern, with bursts containing only generalized spikes accompanying myoclonic activity.⁹ After treatment, EEG became more continuous and rhythmic without epileptiform discharges and with declining serum carbamazepine levels.
• Carbamazepine is incorporated and retained in hair, depending on the blood levels. Sectional hair analysis helps investigators determine if chronic poisoning is an issue.¹⁰

Treatment

Medical Care

• General and supportive measures in carbamazepine toxicity
  • Rapid and thorough evaluation of the patient's status is crucial; pay particular attention to the patient's level of sensorium, the ability to maintain an airway, and the respiratory and hemodynamic status.
  • Patients with severe poisoning require admission to the ICU. Examples of such patients include those who are comatose on arrival to the facility and those with a deteriorating mental status, hypotension, seizures, or respiratory irregularities (eg, respiratory depression, apnea).
  • Therapeutic emesis is not recommended because rapid deterioration in neurostatus may occur, leading to aspiration.
  • Patients with a deep coma, apnea, or respiratory depression may require intubation and mechanical ventilation.
  • Patients with hypotension may need isotonic fluid boluses or inotropic support.
  • All patients require continuous cardiac monitoring for cardiac arrhythmia.
  • All patients with change in mental status require a finger stick glucose and should be given intravenous glucose if the glucose level is low.
• Administration of multiple-dose activated charcoal
  • After the patient's airway, breathing, and circulation are stabilized, therapy with multiple-dose activated charcoal should be started, with doses administered every 4 hours via a nasogastric tube after initial stomach lavage. Obviously, in patients without gag reflexes, the nasogastric tube should not be inserted until after the airway has been protected by endotracheal intubation.
  • Although usually gastric lavage is not usually useful, unless it is performed within an hour of the ingestion of the drug, this is not necessarily the case with a significant overdose of carbamazepine. Sustained-released preparations may persist in the stomach for many hours. Hypomotility may occur. Enterohepatic circulation occurs with carbamazepine overdose. Pharmacobezoars may form in the stomach. Nasogastric tube insertion is necessary to instill charcoal. For all these reasons, nasogastric tube insertion with lavage is indicated, even many hours after the ingestion has occurred.
  • A significant amount of carbamazepine is excreted in the bile. Enterally administered activated charcoal can be used to prevent the primary absorption and reabsorption of carbamazepine, which is excreted in the bile.
  • There are several important drugs that have entero-hepatic circulation and overdoses of these drugs should be treated with multiple doses of charcoal, even after all of the drug has been absorbed. These drugs include phenobarbital, theophylline, and carbamazepine. This procedure is often referred to as "gut dialysis" because drug levels may rapidly fall after this treatment.
  • If sorbitol is used, it should only be given with the first dose of the activated charcoal. Repeat doses of sorbitol may lead to dehydration, electrolyte abnormalities, and even death, especially in young children.
  • Serious carbamazepine poisoning is often complicated by drug-induced GI hypomotility. Severe ileus may interfere with the administration of multiple-dose charcoal and with decontamination of the GI tract. GI hypomotility may result in ongoing drug absorption and prolongation of symptoms.
• Whole bowel irrigation
  • Whole bowel irrigation may be used to treat carbamazepine overdoses with sustained-released preparations or in patients who had a massive ingestion. It can also be used if the formation of concretions or pharmacobezoars is suspected.
  • If the carbamazepine level is not decreasing or is even rising despite repeated doses of activated charcoal, the use of whole bowel irrigation should be strongly considered.
  • Whole bowel irrigation uses preparations that contain polyethylene glycol (PEG), such as Colyte or Go-lightly. PEG decreases the amount of the toxin in the digestive tract without causing dehydration or electrolyte depletion. The dose is 20-40 mL/kg/h until the patient has clear diarrhea.
  • It is contraindicated in children younger than 9 months and in patients with an acute abdominal problem.
  • In young children, the PEG solution should not be cooled in order to avoid hypothermia.¹¹
• Charcoal hemoperfusion
  • Charcoal hemoperfusion has been used to treat patients with life-threatening carbamazepine poisoning.¹² Activated charcoal imbedded in the hemoperfusion cartridge competes with plasma proteins for binding of the drug.
  • Hemoperfusion is limited to the removal of substances from the blood compartment; therefore, patients receiving drugs with a large volume of distribution may require prolonged hemoperfusion.
  • Charcoal hemoperfusion may have a more important role in patients with acute toxicity because of the low intrinsic clearance (see Background).
  • Hemoperfusion may effectively remove the parent drug and its epoxide metabolite.
  • Charcoal hemoperfusion is an important adjuvant therapy in patients with life-threatening carbamazepine poisoning complicated by drug-induced gastrointestinal hypomotility.
  • Repeat hemoperfusion treatments may by necessary until GI motility returns to its previous level.
  • To the author's knowledge, no written guidelines address the use of charcoal hemoperfusion in carbamazepine poisoning. Hence, a common-sense approach is to use charcoal hemoperfusion in the following situations: (1) when associated GI hypomotility or ileus is present and makes the use of activated charcoal ineffective, (2) when the patient's clinical status is deteriorating despite the administration of enteric activated charcoal, and (3) when the patient has a severe life-threatening intoxication that causes deep coma, seizures, arrhythmias, and/or respiratory depression. In these situations, the patient may rapidly deteriorate and die.
• Dialysis
  • Hemodialysis and peritoneal dialysis are ineffective in eliminating carbamazepine from the serum because of the drug's insolubility in water, high protein binding, and relatively large volume of distribution. However, Askenazi et al reported a 10-year old girl with carbamazepine poisoning who was treated successfully using albumin-enhanced continuous venovenous hemodialysis.¹³
  • Yildiz et al reported successful use of continuous venovenous hemodiafiltration (CVVHDF) for the treatment of carbamazepine poisoning in a 2-year old patient after ingestion of controlled-release tablets.¹⁴ Yildiz et al claim that, although more difficult and more expensive, CVVHDF combines both diffusion and convection principles, thus enhancing the clearance of the drug.
  • Bek et al used conventional low-flux hemodialysis in the management of acute carbamazepine overdose in 3 adolescent patients.¹⁵ They conclude that standard low-flux hemodialysis may be used for treatment of mild carbamazepine overdose or when hemoperfusion is not available.

Consultations

• If the patient's history suggests suicidal intent, consult a child psychiatrist.
• In all cases involving an accidental ingestion, personnel from social services or child protective services should be notified to evaluate the patient's home situation.
• Consultation with a toxicologist or with poison control center personnel should be considered.
• Consultation with a nephrologist should be obtained early if charcoal hemoperfusion may be needed.

Medication

Decontamination agents

Consider activated charcoal decontamination in any patient who presents within 4 hours of ingestion, or even later if the patient has an overdose with a sustained release preparation or has evidence of significant toxicity.

Activated charcoal (Actidose-Aqua, Liqui-Char, Insta-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. Prevents absorption by adsorbing drug in the 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. Does not dissolve in water.
For maximum effect, administer within 30 min after poison ingestion. The usual dose is 1 g/kg but never less than 30 g. It can be repeated in a dose of 0.5 g/kg q2h or 1 g/kg q4h when indicated, until the patient is asymptomatic and/or toxic drug levels have decreased to safe levels if measurable.
Sorbitol may be added to activated charcoal to improve its palatability. However, as mentioned above, it should never be used with multiple doses of charcoal, and never in children younger than 1 y.

Dosing

Adult

30-100 g, 1 g/kg (minimum of 30 g), , or 10 times the weight of ingested poison given PO as susp in 4-8 oz of water; may repeat with 0.5 g/kg PO q2h or 1 g/kg q4h

Pediatric

<1 year: 1 g/kg PO as aqueous slurry (mix in at least 240 mL water); limit to a single dose and do not use sorbitol
>1 year: Administer as in adults; do not exceed sorbitol dose of 1.5 g/kg body weight

Interactions

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

Contraindications

Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies

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

Not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before giving activated charcoal; after emesis with ipecac, patient may not tolerate activated charcoal for 1-2 h, for this reason many experts advocate administering activated charcoal without inducing emesis first; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black, for this reason many experts advocate administering activated charcoal without inducing emesis first

Follow-up

Further Inpatient Care

Discharge patients with carbamazepine toxicity if the following conditions are met:

• The patient is symptom free and the carbamazepine level has decreased to less than 4-8 mg/L. Obviously, patients with significant toxicity should be admitted and patients with life threatening or potentially life-threatening signs and/or symptoms should be admitted to an ICU.
• An exception to decreasing the carbamazepine level to a subtherapeutic level is in the patient who is taking carbamazepine for seizure control. This patient may be discharged with a therapeutic serum level of carbamazepine or another substituted anticonvulsant.
• After being “medically cleared," the patient should not be discharged from the hospital until personnel from social services or child protective services or a psychiatrist agrees, if the case required the notification of these professionals.

Further Outpatient Care

• Patients should follow up with their primary care provider within 24-48 hours after their discharge.
• The physician should reevaluate the patient's condition and discuss the prevention of future episodes.

Deterrence/Prevention

• A discussion with the patient's parents concerning the safe storage and dosage of medications is essential.
• Parents should be provided the toll-free telephone number for the American Association of Poison Control Centers (800-222-1222).

Patient Education

• A discussion regarding the prevention of unintentional ingestion is an important component of the routine care of the child.
• The patient's parents should be taught how to safely store medications.
• 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

When patients with suspected carbamazepine poisoning are treated, the following services should be notified:

• The American Association of Poison Control Centers: This organization maintains a nationwide database of all the poisoning cases. Contacting the regional or state poison control center in cases of carbamazepine poisoning helps in maintaining the accuracy of this database and also helps in managing the case according to current guidelines. Information from this database can also help in ensuring that patients receive the necessary follow-up care.
• Social services: Once the patient is admitted to the hospital, social services should be contacted to evaluate the patient's home situation. Social services personnel may later notify child protection services if needed.
• Child protection services
  • If the patient's history strongly suggests a disturbed home environment that may have resulted in the neglect of the child, notifying child protection services may be prudent. However, in most cases, a consultation with social services personnel is sufficient.
  • Psychiatry should be consulted if the patient may be suicidal.
  • Failure to consider and appropriately treat carbamazepine toxicity, when faced with a consistent history and/or toxidrome, can lead to medicolegal problems.

Multimedia

Media file 1: Chemical structure of carbamazepine.

References

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Keywords

carbamazepine overdose, carbamazepine poisoning, acute carbamazepine poisoning, accidental carbamazepine poisoning, Tegretol, Tegretol overdose, Tegretol toxicity, Carbatrol, Epitol, trigeminal neuralgias, tonic-clonic epilepsy, partial epilepsy, manic depression, treatment, diagnosis

Contributor Information and Disclosures

Author

Muhammad Waseem, MD, Associate Professor of Emergency Medicine in Clinical Pediatrics, Weill Medical College of Cornell University; Consulting Staff, Department of Pediatrics, Bronx Lebanon Hospital; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center
Muhammad Waseem, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Joel R Gernsheimer, MD, FACEP, Visiting Associate Professor, Department of Emergency Medicine, Attending Physician and Director of Geriatric Emergency Medicine, State University of New York Downstate Medical Center
Joel R Gernsheimer, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Nicholas D Caputo, MD, House Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center/Weill Cornell Medical College
Nicholas D Caputo, MD is a member of the following medical societies: American College of Emergency Physicians and Emergency Medicine Residents Association
Disclosure: Nothing to disclose.

Medical Editor

William T Zempsky, MD, Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
William T Zempsky, 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 financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

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.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Girish G Deshpande, MD, to the original writing and development of this article.

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