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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 8  |  Issue : 6  |  Page : 299-301

Acute carbamazepine toxicity in a child: A case report


Department of Pediatrics, Division of Pediatric Critical Care, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission03-Aug-2021
Date of Decision27-Sep-2021
Date of Acceptance04-Oct-2021
Date of Web Publication19-Nov-2021

Correspondence Address:
Dr. Suresh Kumar Angurana
Department of Pediatrics, Division of Pediatric Critical Care, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_65_21

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  Abstract 


Carbamazepine is a commonly prescribed antiepileptic drug with a potential to cause fatal toxicity in acute overdose in children. Symptoms of acute toxicity include central nervous system depression, seizures, anticholinergic toxidrome, and arrhythmias. We report a 5 year old male child with accidental carbamazepine toxicity treated sussessfully with good suppotrive management. Intestinal decontamination therapies may be beneficial if used at the appropriate time. Multidose activated charcoal may be used if multiple controlled release tablets are ingested. Extracorporeal therapies for drug removal may be required in life-threatening toxicity to reduce plasma drug levels and hasten recovery. Appropriate and timely management leads to excellent neurological outcome.

Keywords: Activated charcoal, antiepileptic drug toxicity, carbamazepine, extracorporeal removal, multidose activated charcoal, pediatric toxicity


How to cite this article:
Randhawa MS, Sharma P, Angurana SK, Bansal A. Acute carbamazepine toxicity in a child: A case report. J Pediatr Crit Care 2021;8:299-301

How to cite this URL:
Randhawa MS, Sharma P, Angurana SK, Bansal A. Acute carbamazepine toxicity in a child: A case report. J Pediatr Crit Care [serial online] 2021 [cited 2021 Nov 27];8:299-301. Available from: http://www.jpcc.org.in/text.asp?2021/8/6/299/330729




  Introduction Top


Carbamazepine is a commonly used antiepileptic drug in children and adults. Acute overdose of carbamazepine has the potential to cause central nervous system (CNS) depression, anticholinergic toxidrome, and arrhythmias.[1] In acute overdose, decontamination measures and supportive care are the key to management in mild cases. Severe, life-threatening toxicities may warrant extracorporeal therapies for drug removal. There were 1556 cases of carbamazepine overdose reported in the US in 2019 out of which 111 were in children below 5 years of age. Severe toxicity was noted in 5.7% (n = 88) and 0.2% (n = 3) died.[2] We report a 5-year-male who presented with acute overdose with carbamazepine leading to severe life-threatening manifestations. He was successfully managed with decontamination, extracorporeal therapy (hemodialysis), and supportive care in pediatric intensive care unit (PICU) and recovered well.


  Case Report Top


A 5-year-male was referred to our emergency department (ED) with a history of progressive drowsiness, few episodes of nonprojectile vomiting, and four episodes of generalized tonic-clonic seizures, each lasting 3–4 min, without gaining sensorium between seizures. He was taken to a primary care facility where he received intravenous phenytoin, fluids, intubated, and referred to our ED. On triage assessment, he was intubated, had poor respiratory efforts, with equal bilateral air entry and no added sounds on chest examination, and saturation was 96%. He had tachycardia (142/min), well palpable central and peripheral pulses, capillary refill time of 2 seconds, and blood pressure of 94/66 mm Hg. His Glasgow Coma Scale was E1V1M4, pupils were dilated he had, intermittent dystonic movements, and blood glucose was 82 mg/dL. He also had hyperthermia and dry skin.

On review of the history, the parents recalled that the child had accidently consumed 4–5 tablets (controlled release) of carbamazepine (400 mg/tab), amounting to 80–100 mg/kg of carbamazepine. The diagnosis of carbamazepine toxicity was made. He was continued on mechanical ventilation, administered multidose activated charcoal (MDAC), 1 g/kg, 6 doses at 4 hourly intervals, and phenytoin was discontinued. Carbamazepine blood levels were 30 mg/L (normal: 4–12 mg/L). Over the next 24 h, he remained deeply comatose with intermittent dystonias even after decontamination therapy and supportive measures. At this time point, he underwent one cycle (for 3 h) of hemodialysis. Soon after, the sensorium of the child improved, and he was extubated in the next 24 h and discharged after a PICU stay of 72 h with premorbid neurological status. Parents were advised to store the drugs, toxins, and dangerous substances away from the reach of children and adequate supervision.


  Discussion Top


We report a 5-year-old male, who had toxic ingestion of carbamazepine and recovered following decontamination therapy, hemodialysis, and supportive care. Carbamazepine is commonly used drug for focal seizures, neuralgic pain syndromes, and bipolar disorders as it is widely available, affordable, and effective. However, it is also one of the drugs that can result in fatal overdose.[3] The usual therapeutic dose of carbamazepine is 10–30 mg/kg/day in children. As carbamazepine induces its own metabolism, its half-life decreases with chronic use and dose as high as 30 mg/kg/day may not produce toxic effects. However, in acute overdose, without any prior exposure, even 20 mg/kg may induce fatal toxicity as the drug may remain in the system for longer and peak levels may appear much after the ingestion. Higher the dose ingested, more severe are the symptoms. A controlled-release formulation may stay in the intestines for a long time and slowly release the drug causing peak levels to appear as long as 72–96 h after ingestion. These properties make it one of the “one pill can kill” drugs for toddlers as a single 400 mg controlled-release tablet may cause significant toxicity.[4] Therapeutic range of carbamazepine in the plasma is 8–12 mg/L. Levels >40 mg/L cause severe toxicity and warrant aggressive therapy.[1]

Carbamazepine poisoning manifests as symptoms related to CNS, anticholinergic effects, and cardiovascular system. The CNS symptoms include blurring of vision, nystagmus, vertigo, headaches, diplopia, cerebellar signs, seizures, dyskinesias, dystonic movements, and finally, hallucinations and coma. The anticholinergic effects include mydriasis, dry flushed skin, tachycardia, and hyperthermia. The sodium channel blocking properties may cause arrhythmias, conduction abnormalities in form of prolonged QRS duration, progressing to conduction blocks, and life-threatening arrhythmias. The direct negative inotropic effect may cause hypotension. Other side effects such as drug rash and bone marrow suppression are usually seen in chronic rather than acute overdose.[3]

As there is no specific antidote available for carbamazepine toxicity, supportive care is of paramount importance. Initial care must focus on stabilization of the airway, breathing, and circulation. Children with severe CNS depression and unstable airway need endotracheal intubation and mechanical ventilation. Hypotension, if present, usually responds well to fluid boluses. Seizures should be controlled with benzodiazepines. The antiepileptic drugs with sodium channel blocking action must be avoided. A 12-lead electrocardiogram must be obtained to document QRS duration and conduction blocks and in severe toxicity, should be repeated 12 hourly. A QRS duration of >110 ms warrants treatment with sodium bicarbonate, targeting a duration <100 ms.[4]

Decontamination measures may prove beneficial in carbamazepine toxicity. Gastric lavage may be done if child presents within 1 h of ingestion. However, the clinical benefit has not been proven and caution must be observed to prevent aspiration.[5] Activated charcoal (AC) may be used within 1–2 h of ingestion. Any CNS depression with an unstable airway is a contraindication to AC. As there is no convincing evidence of clinical benefit of AC, intubation is not warranted solely for giving AC to the children who do not otherwise need an invasive airway device.[6] Due to the presence of controlled release forms of carbamazepine and significant entero-hepatic circulation, MDAC may be used especially in cases with severe toxicity and persistent symptoms, in dose of 1 gram/kg for first dose, and 0.5 g/kg subsequently at 4–6 hourly intervals till resolution of symptoms.[7] One must auscultate for adequate bowel sounds before administration of AC and MDAC.[7]

Carbamazepine is a small molecule (239 Dalton), 75% protein bound and has a high volume of distribution. In acute poisoning, the large amounts of nonprotein bound drug may be present in the plasma which can be removed by extracorporeal therapies. Hemodialysis has been recommended as the preferred modality and hemoperfusion and continuous renal replacement therapy as alternatives.[8] Peritoneal dialysis and plasma exchange are not helpful. Indications of extracorporeal therapy include life-threatening arrhythmias, persistent encephalopathy, incessant seizures, and prolonged mechanical ventilation. Hemodialysis eliminates the unbound form of the carbamazepine molecule from the plasma through diffusion across a semipermeable membrane. It has been used successfully in the past for carbamazepine toxicity.[9],[10] Elimination may be enhanced by adding 5% albumin to the dialysate or using charcoal filters, but these are costly with little clinical benefit.[11] There has been some interest in using intravenous lipid emulsion instead of extracorporeal therapy, but larger trials are needed.[12] Extracorporeal therapies may be stopped once drug levels are below toxic range, or the patient has become asymptomatic. Decontamination modalities may be continued for the duration of extracorporeal therapy to prevent further absorption from the intestinal tract.[8] Even asymptomatic children with consumption of doses >20 mg/kg should be observed in the emergency room for at least 8 h for symptom onset. Symptomatic children should be managed as above and kept till 72 h or symptom resolution, whichever is longer.[4]

Carbamazepine poisoning is not uncommon in children. With adequate supportive care, decontamination, and extracorporeal therapy, if indicated, the outcome is generally good.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's legal guardian has given the consent for images and other clinical information to be reported in the journal. The patient's legal guardian understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

We acknowledge the contributions of Dr. Sudeep KC and Dr. Karthi Nallasamy in clinical management of the case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Al Khalili Y, Sekhon S, Jain S. Carbamazepine Toxicity. StatPearls. Treasure Island (FL): StatPearls Publishing; 2021. Available from: http://www.ncbi.nlm.nih.gov/books/NBK507852/. [Last accessed on 2021 Apr 21].  Back to cited text no. 1
    
2.
Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Brooks DE, Dibert KW, et al. 2019 annual report of the American association of poison control centers' national poison data system (NPDS): 37th annual report. Clin Toxicol (Phila) 2020;58:1360-541.  Back to cited text no. 2
    
3.
Durelli L, Massazza U, Cavallo R. Carbamazepine toxicity and poisoning. Incidence, clinical features and management. Med Toxicol Adverse Drug Exp 1989;4:95-107.  Back to cited text no. 3
    
4.
Carbamazepine Toxicity • LITFL • Toxicology Library Toxicants. Life Fast Lane • LITFL; 2019. Available from: https://litfl.com/carbamazepine-toxicity-tox-library/. [Last accessed on 2021 Apr 24].  Back to cited text no. 4
    
5.
Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J, et al. Position paper update: Gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila) 2013;51:140-6.  Back to cited text no. 5
    
6.
Chyka PA, Seger D, Krenzelok EP, Vale JA; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005;43:61-87.  Back to cited text no. 6
    
7.
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.  Back to cited text no. 7
    
8.
Ghannoum M, Yates C, Galvao TF, Sowinski KM, Vo TH, Coogan A, et al. Extracorporeal treatment for carbamazepine poisoning: Systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol 2014;52:993-1004.  Back to cited text no. 8
    
9.
Ram Prabahar M, Raja Karthik K, Singh M, Singh RB, Singh S, Dhamodharan J. Successful treatment of carbamazepine poisoning with hemodialysis: A case report and review of the literature. Hemodial Int 2011;15:407-11.  Back to cited text no. 9
    
10.
Yaylacı S, Demir MV, Acar B, Sipahi S, Tamer A. Successful treatment of excessive dose of carbamazepine. Indian J Pharmacol 2012;44:417-8.  Back to cited text no. 10
    
11.
Churchwell MD, Pasko DA, Smoyer WE, Mueller BA. Enhanced clearance of highly protein-bound drugs by albumin-supplemented dialysate during modeled continuous hemodialysis. Nephrol Dial Transplant 2009;24:231-8.  Back to cited text no. 11
    
12.
Sohn JT. Lipid Emulsion Treatment for Carbamazepine Toxicity; 2021. Available from: https://pediatrics.aappublications.org/content/lipid-emulsion-treatment-carbamazepine-toxicity. [Last accessed on 2021 Apr 24].  Back to cited text no. 12
    




 

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