A Case of Carbamazepine Intoxication in a Young Boy

The Journal of Emergency Medicine, Vol. 39, No. 5, pp. 655– 661, 2010 Copyright © 2010 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$–see front matter

Letters to the Editor e A CASE OF CARBAMAZEPINE INTOXICATION IN A YOUNG BOY

the patient. The serum carbamazepine level was 25 ug/mL on the third day of hospitalization. When he was discharged on the fourth day of hospitalization, complete blood count, liver and kidney function tests, prothrombin time, active partial thromboplastin time, and brain magnetic resonance imaging were all within normal limits. The patient was treated with phenytoin, two doses for a total of 5 mg/kg/ day, and was followed-up for 2 months by our pediatric polyclinics. He did not have any seizures during this period and remained with normal neurological function. In acute carbamazepine intoxication, the neurological system is primarily affected. The signs range from nystagmus, ataxia, dysarthria, lethargy, and seizures to coma and respiratory depression, many of which our patient had (3). In adults, serum concentrations ⬎ 40 ␮g/mL are usually predictive of serious toxicity, and this blood level is associated with coma, respiratory depression, seizures, and dysrhythmias (4). However, children are known to develop severe manifestations at lower serum concentrations (5–7). It is reported that, in children, this peak level varies between 27 and 35 ␮g/mL (5–7). The reason for this lower threshold is unknown (3). It should be noted that, of the neurological manifestations of severe toxicity, coma without hypoxia or hypotension is generally not associated with residual neurological sequelae; however, status epilepticus is a rare but ominous complication (1,3). In our patient, the plasma level of carbamazepine was 25 ␮g/mL, but we measured this value on the third day of hospitalization. Peak plasma levels of carbamazepine would have been higher had it been measured on the first day of admission. Although seizures were controlled with diazepam, stupor was observed in our patient with no dysrhythmia, hypotension, cardiac toxicity, or hypoxia. The concern for cardiac toxicity must always be considered when dealing with carbamazepine ingestion. One-third of patients will characteristically develop a sinus tachycardia that is secondary to the anticholinergic effects (3). Hypotension, conduction delays, and QTc (corrected QT time in electrocardiography) prolongation (⬎ 420 ms) have been reported (3). In our patient, the items mentioned above were not found. The management of carbamazepine overdoses is supportive. Activated charcoal, which binds carbamazepine effectively, should be given early (3). Multiple-dose activated charcoal prevents enterohepatic recirculation and

e To the Editor: Carbamazepine, a commonly used anticonvulsant, is generally a safe drug. However, it has at times been associated with cases of severe toxicity and death. Its pharmacological properties include sedation, anticholinergic, antidysrhythmic, muscle relaxant, antidiuretic, and antidepressant effects (1). Carbamazepine is available in enteral solid and suspension formulations (2). In contrast to the solid formulation that is known to have slow and unpredictable absorption, therapeutic loading doses of carbamazepine suspension provide quick and predictable absorption in both children and adults (2). Pharmacokinetic studies have demonstrated rapid absorption of the suspension resulting in peak and therapeutic concentrations within 2 h of ingestion (2). In this letter, we discuss the case of a young boy who was followed for epilepsy for 2 years and who had a carbamazepine tablet intake equal to 100 mg/kg. A 7-year-old boy presented to our Emergency Department due to loss of consciousness. He had a history of epilepsy diagnosed 2 years prior at another center and was treated with carbamazepine pills at a dose of 200 mg twice a day. It was determined that 6 h before presentation, he took 10 carbamazepine pills, which was equal to 100 mg/ kg, and 1 h afterward he became unconscious. He did not develop seizures, but vomited three times at home. His family history was unremarkable. On physical examination, he appeared ill in general. On neurological examination, he had decreased level of consciousness and stupor; Glasgow Coma Scale score was 6. The remainder of the physical examination was normal. On laboratory examination, complete blood count, liver, renal function tests, serum electrolytes, arterial blood gas analysis, prothrombin time, and active partial thromboplastin time were all in the normal range, and urinalysis and electrocardiogram were similarly normal. The patient was hospitalized with a diagnosis of acute carbamazepine intoxication and was followed in the intensive care unit. Gastric lavage was performed and six daily doses of activated charcoal, 1 gm/kg/dose, were given. The patient did not develop cardiac dysrhythmias. Twelve hours after the hospitalization he began seizing, which was treated with diazepam. Supportive care was also given to 655

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should be used if no contraindication exists (e.g., anticholinergic ileus) (8). Cardiac monitoring should take place, and seizures should be treated with benzodiazepines (3). Early treatment is very important in these situations. In acute carbamazepine intoxication, due to the wide distribution capacity and high binding to plasma proteins, conventional hemodialysis is not useful. However, there are few studies that report that albumin-enhanced continuous venovenous hemodialysis may be an optimal and cost-effective option for the treatment of toxic-level ingestions of proteinbound drugs like carbamazepine that are not amenable to clearance by conventional dialysis protocols (9). Symptomatic treatment was given to our patient consistent with the literature, and there was no need to perform more invasive treatment modalities like hemodialysis or albumin-enhanced continuous venovenous hemodialysis. In summary, we present the case of a 7-year-old boy with epilepsy who had a significant carbamazepine tablet intake, equal to 100 mg/kg, and presented with coma but eventually was discharged neurologically intact. Murat Dog˘an, MD Department of Pediatric Endocrinology Faculty of Medicine Yuzuncu Yil University Van, Turkey Cahide Yılmaz, MD Department of Pediatric Neurology Faculty of Medicine Yuzuncu Yil University Van, Turkey Hayrettin Temel, MD Department of Pediatrics Faculty of Medicine Yuzuncu Yil University Van, Turkey Hüseyin Çaksen, MD Department of Pediatric Neurology Faculty of Medicine Yuzuncu Yil University Van, Turkey Gökmen Tas¸kın, MD Department of Pediatrics Faculty of Medicine Yuzuncu Yil University Van, Turkey doi:10.1016/j.jemermed.2008.10.007

REFERENCES 1. Spiller HA. Management of carbamazepine overdose. Pediatr Emerg Care 2001;17:452– 6. 2. Cohen H, Howland MA, Luciano DJ, et al. Feasibility and pharmacokinetics of carbamazepine oral loading does. Am J Health Syst Pharm 1998;55:1134 – 40. 3. Perez A, Wiley JF. Pediatric carbamazepine suspension overdose— clinical manifestations and toxicokinetics. Pediatr Emerg Care 2005;21:252– 4. 4. Hojer J, Malmlund HO, Berg A. Clinical features in 28 consecutive cases of laboratory confirmed massive poisoning with carbamazepine alone. J Toxicol Clin Toxicol 1993;31(3):449 – 8. 5. Macnab AJ, Birch P, Maccready J. Carbamazepine poisoning in children. Pediatr Emerg Care 1993;9:195– 8. 6. Miles MV, Lawless ST, Tennison MB, et al. Rapid loading of critically ill patients with carbamazepine suspension. Pediatrics 1990;86:263– 6. 7. Weaver DF, Camfield P, Fraser A. Massive carbamazepine overdose: clinical and pharmacological observations in five episodes. Neurology 1988;38:755–9. 8. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1999; 37:731–51. 9. Askenazi DJ, Goldstein SL, Chang IF, Elenberg E, Feig DI. Management of a severe carbamazepine overdose using albuminenhanced continuous venovenous hemodialysis. Pediatrics 2004;113:407–9.

e A RARE CAUSE OF JUNCTIONAL RHYTHM CAUSING SYNCOPE; MAD HONEY INTOXICATION e To the Editor: A 50-year-old man was admitted to our Emergency Department (ED) with complaints of blurred vision, dizziness, and a syncopal event 30 min prior without chest pain, palpitation, or dyspnea. He did not have any cardiovascular or systemic illnesses and was not taking any medication or herbal products. In his past medical history, he described a syncopal attack 6 months before that occurred after a meal and his cardiovascular evaluation was reported normal at that time. The patient had eaten a breakfast that included two bowls of honey 3 h before arrival. Physical examination revealed a pulse rate of 44 beats/min and a blood pressure of 80/55 mm Hg. An electrocardiogram (ECG) showed junctional rhythm with a ventricular rate of 44 beats/min (Figure 1). Blood chemistry and complete blood count were within normal limits. Atropine sulfate 3 mg was administered intravenously within 10 min but sinus rhythm was not restored. The patient became more hypotensive and the pulse rate decreased to 36 beats/min. Due to the ongoing symptoms and worsening clinical condition, intravenous saline infusion was started with boluses and a temporary trans-