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Pediatric Carbamazepine Toxicity Treatment & Management

  • Author: Muhammad Waseem, MD, MS; Chief Editor: Timothy E Corden, MD  more...
 
Updated: Apr 22, 2016
 

Medical Care

General and supportive measures in carbamazepine toxicity are as follows[26] :

  • 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 fingerstick glucose assay and should be given intravenous glucose if the glucose level is low.

Activated charcoal and lavage

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 with an impaired gag reflex, the nasogastric tube should not be inserted until after the airway has been protected by endotracheal intubation.

Although gastric lavage is not recommended for routine use in the management of poisoning,[27] a significant overdose of carbamazepine can be an exception to that rule. 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 those 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. Enterically administered activated charcoal can be used to prevent the primary absorption and reabsorption of carbamazepine, which is excreted in the bile.

Carbamazepine is one of several important drugs that have enterohepatic circulation (others are phenobarbital and theophylline), which allows treatment of overdose with multiple doses of charcoal, even after all of the drug has been absorbed. 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, as that could result in hypothermia.[27]

Charcoal hemoperfusion

Charcoal hemoperfusion has been used to treat patients with life-threatening carbamazepine poisoning.[28] 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; thus, 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:

  • Associated GI hypomotility or ileus is present and makes the use of activated charcoal ineffective
  • The patient's clinical status is deteriorating despite the administration of enteric activated charcoal
  • The patient has a severe life-threatening intoxication that causes deep coma, seizures, arrhythmias, and/or respiratory depression; such patients are at risk for rapid deterioration and death

Dialysis

Peritoneal dialysis is ineffective in eliminating carbamazepine from the serum because of the drug's insolubility in water, high protein binding, and relatively large volume of distribution. It had been thought that hemodialysis is also ineffective in treating carbamazepine toxicity for the same reasons. However, several case reports have documented successful management of severe carbamazepine toxicity with hemodialysis. Askenazi et al reported a 10-year old girl with carbamazepine poisoning who was treated successfully using albumin-enhanced continuous venovenous hemodialysis.[29]

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.[30] These authors 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 three adolescent patients.[31] They conclude that standard low-flux hemodialysis may be used for treatment of mild carbamazepine overdose or when hemoperfusion is not available.

Harder et al reported a case in an adult with acute carbamazepine overdose who was successfully treated with hemodialysis followed by continuous venovenous hemodialysis. The patient’s clinical status and her levels of carbamazepine and its epoxide metabolite markedly and rapidly improved with this treatment.[32]

Prabahar et al successfully treated an adult with severe carbamazepine toxicity using “simple hemodialysis” because hemoperfusion was not available at their facility. Their report also included a review of the available literature on this subject. They concluded that hemodialysis was an effective and relatively safe way of managing severe carbamazepine toxicity, especially when charcoal hemoperfusion is not available.[33]

A systematic review of extracorporeal treatment of carbemazepine poisoning by Ghannoum et al concluded that intermittent hemodialysis is the preferred extracorporeal treatment, but intermittent hemoperfusion or continuous renal replacement therapies are alternatives if hemodialysis is not available.[34]

Ghannoum et al recommend extracorporeal treatment for patients with multiple seizures refractory to treatment or with life-threatening dysrhythmias. They suggest it for patients with prolonged coma or respiratory depression requiring mechanical ventilation and for those with significant, persistent toxicity, particularly when multiple-dose activated charcoal and supportive measures fail to reduce carbamazepine concentrations. Extracorporeal treatment should be continued until clinical improvement becomes apparent or the serum carbamazepine concentration falls below 10 mg/L.[34]

Next

Consultations

See the list below:

  • 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.
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Contributor Information and Disclosures
Author

Muhammad Waseem, MD, MS Associate Professor of Emergency Medicine in Clinical Pediatrics, Associate Professor of Clinical Healthcare Policy and Research, Weill Medical College of Cornell University; Consulting Staff, Department of Emergency Medicine, Lincoln Medical and Mental Health Center

Muhammad Waseem, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, American Heart Association, Society of Critical Care Medicine, Society for Simulation in Healthcare, 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, American Geriatrics Society

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, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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: Received salary from Merck for employment.

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, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

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.

Acknowledgements

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

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Chemical structure of carbamazepine.
 
 
 
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