Carbamazepine Intoxication Research Articles

Management of acute carbamazepine poisoning: A narrative review

Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine (CBZ) poisoning. The objective of this review is to provide currently available information on acute CBZ poisoning, including its management, by describing and summarizing various therapeutic methods for its treatment according to previously published studies. Several treatment methods for CBZ poisoning will be briefly introduced, their advantages and disadvantages will be analyzed and compared, and suggestions for the clinical treatment of CBZ poisoning will be provided. A literature search was performed in various English and Chinese databases. In addition, the reference lists of identified articles were screened for additional relevant studies, including non-indexed reports. Non-peer-reviewed sources were also included. In the present review, 154 articles met the inclusion criteria including case reports, case series, descriptive cohorts, pharmacokinetic studies, and in vitro studies. Data on 67 patients, including 4 fatalities, were reviewed. Based on the summary of cases reported in the included articles, the cure rate of CBZ poisoning after symptomatic treatment was 82% and the efficiency of hemoperfusion was 58.2%. Based on the literature review, CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage. In severe cases, extracorporeal treatment is recommended, with hemodialysis as the first choice.

カルバマゼピン中毒により下眼瞼向き眼振を認めた薬剤性めまい症例

We report the case of a 33-year-old man who presented with disequilibrium and downbeat nystagmus. Balance testing showed failure of visual suppression of caloric nystagmus with insufficient optokinetic nystagmus responses, suggesting central vestibular dysfunction. However, MRI showed no lesions in the brain, including in the cerebellum. The patient had been diagnosed previously as having epilepsy, and the convulsions had remained under control for more than 10 years with a maintenance dose of carbamazepine (900mg/day). Blood tests revealed a serum level of carbamazepine of 10.7mEq/l, which was over the therapeutic range (4.0-10.0mEq/l). Therefore, his carbamazepine dose was reduced, and with a reduction of the dose to 600mg/day, his disequilibrium and downbeat nystagmus gradually disappeared, along with a decrease in return of the serum level of carbamazepine to the therapeutic range. Therefore, we diagnosed the disequilibrium with downbeat nystagmus in this patient as having been caused by carbamazepine intoxication. Although carbamazepine is metabolized by CYP3A4 in the liver, elevated levels of the drug have been reported in cases of renal failure. As he also suffered from polycystic kidneys, we consider that the progressive renal dysfunction in our patient could have precipitated the carbamazepine intoxication.

難治性徐脈より心肺停止を呈し体外循環導入にて救命し得たカルバマゼピン中毒の1例(A case of carbamazepine intoxication with cardiopulmonary arrest caused by intractable bradycardia that was treated with extracorporeal circulation)

要旨カルバマゼピンは抗てんかん薬で，中毒症状としてめまいや意識障害，不整脈が認められることが多い。カルバマゼピン過量服薬から徐脈性不整脈，心肺停止に至り体外循環を導入し救命した症例を経験した。症例は54歳の女性，既往に統合失調症がある。搬送当日，朝から希死念慮のためカルバマゼピンを過量服薬し，自宅で倒れているところを発見した家族が救急要請した。病院到着後に徐脈から心停止に移行した。心拍再開したが薬剤抵抗性の徐脈を認めたためVA–ECMOを導入した。入院4日目にVA–ECMOを離脱，10日目に人工呼吸器を離脱し35日目に退院となった。カルバマゼピンはナトリウムチャネルブロックの作用を有しており，催不整脈作用を有する。過量服薬時の徐脈性不整脈は治療抵抗性のため，循環不全もしくは心停止に至る症例ではVA–ECMOの導入が効果的であることが示唆された。

Severe Carbamazepine Toxicity Treated with Continuous Venovenous Hemofiltration at Palestine Medical Complex: Two Case Reports

Carbamazepine intoxication is not uncommon and accounts for many cases of poisoning among anticonvulsive medications users. Since there is no specific antidote for carbamazepine overdose, management is limited to gastric decontamination and supportive therapy. With its high protein binding, the role of extracorporeal elimination in carbamazepine intoxication is still questionable. Here two cases of severe carbamazepine intoxication are presented; the cases were brought to the emergency department after the ingestion of 12,000 mg of controlled release carbamazepine for the first case, and unknown amounts of the same drug for the second case. Both cases were presented with altered mental status, convulsion, and high serum carbamazepine levels of more than 20 mcg/mL. They were intubated and treated with continuous venovenous hemofiltration, after which carbamazepine levels declined significantly along with subsequent clinical improvement and complete neurological recovery. Both cases were discharged home for further psychiatric care.

Clinical Features, Intensive Care Needs, and Outcome of Carbamazepine Poisoning in Children.

Carbamazepine is commonly used antiseizure medication with a narrow therapeutic range. The data on carbamazepine poisoning in children from India is limited. In this retrospective study, the authors reported 10 children with carbamazepine poisoning admitted to pediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India over a period of 8 y (2013 to 2020). The median age was 5.5 (4.3-6) y and 60% cases were males. All had accidental ingestion and the dose ingested was 96 (80-103) mg/kg. The common clinical features were drowsiness (100%), tachycardia (80%), vomiting (60%), seizures (60%), respiratory failure (60%), and dystonia (50%). At admission, 60% children had coma. The treatment included gastric lavage (70%), single-dose-activated charcoal (60%), multidose-activated charcoal (30%), mechanical ventilation (60%), and dialysis (20%). The duration of PICU and hospital stay was 36 (22-45) h and 48 (48-60) h, respectively. There was no mortality.

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

Successful Multiorgan Donation From a Brain-dead Donor Following Liquid Nicotine Voluntary Intoxication: A Case Report.

Successful Multiorgan Donation From a Brain-dead Donor Following Liquid Nicotine Voluntary Intoxication: A Case Report.

The effect of multidrug exposure on neurological manifestations in carbamazepine intoxication: a nested case-control study

BackgroundIn acute intoxication, carbamazepine concentration above 40 mcg/ml is associated with a risk of severe neurological consequences, including depressed consciousness, respiratory depression, cardiac conduction disorders, seizures, and death. Carbamazepine intoxication is often associated with the use of concomitant medications. However, the effect of exposure to other central-nervous-system (CNS) acting medications on the neurological manifestations of carbamazepine toxicity has not been evaluated.ObjectiveTo examine the effect of exposure to CNS-acting medications on the neurological effects of carbamazepine toxicity.MethodsA retrospective nested case-control study of all patients > 18 years of age, with at least one test of carbamazepine levels > 18 mcg/ml recorded at the Hadassah Hospital Central Laboratory, between the years 2004–2016. Sociodemographic and clinical data were collected from the computerized medical records, and the characteristics of patients with and without severe neurological symptoms of carbamazepine intoxication were compared.ResultsEighty patients were identified. In bivariate analyses, the odds of severe neurological symptoms was higher in patients with antidepressants use (odds ratio 8.7, 95% confidence interval: 1.8–41.2, p = 0.007), benzodiazepines use (8.6, 2.0–37.1, p = 0.004), and carbamazepine concentration above 30 mcg/ml (8.1, 1.9–33.3, p = 0.004).Multivariate models demonstrated that antidepressants and benzodiazepines were associated with severe neurological manifestations during carbamazepine intoxication, independently of carbamazepine concentration over 30 mcg/ml.ICU admission was associated in multivariate analysis with antidepressants (but not benzodiazepines) use, and with carbamazepine levels > 30 mcg/ml.ConclusionsAmong patients with carbamazepine intoxication, severe neurological symptoms are associated with exposure to benzodiazepines or antidepressants and with carbamazepine levels higher than 30 mcg/ml.

Role of Charcoal as a limitation of a carbamazepine poisoning

Role of Charcoal as a limitation of a carbamazepine poisoning

Use of Charcoal Hemoperfusion and High-Flux Hemodialysis in Carbamazepine Intoxication: Two Case Reports

Introduction: Carbamazepine (CBZ) is a drug used in the treatment of neurological and psychiatric disorders. Intoxication with CBZ is a serious condition that can result in coma, hemodynamic instability and death. Urgent management of CBZ intoxication is life saving and extracorporeal methods are used for removal of CBZ. It is also known that CBZ is highly protein-bound and charcoal hemoperfusion is the most effective extracorporeal elimination. We know that hemodialysis is also a technique for management of this drug. Case Presentation: We present two cases of CBZ intoxication, treated with two different methods, charcoal hemoperfusion and high-flux hemodialysis. The first patient who was receiving CBZ treatment for anxiety disorder was admitted to Bakirkoy Dr. Sadi Konuk Educational and Research Hospital, Istanbul, Turkey on 11th of December 2017, with complaints of dizziness and blurred vision. Vital signs were stable. Laboratory tests were normal. Serum CBZ level was 56 μg/mL (reference 4 - 12 μg/mL). The CBZ level was 15.6 μg/mL after charcoal hemoperfusion for 3 hours. The second patient was admitted to the emergency room on the 5th of February 2015, with blurred consciousness. The patient had taken CBZ for suicide. The CBZ level was 33 μg/mL and was 14.86 μg/mL after hemodialysis with high-flux membrane for 4 hours. Serum CBZ level decreased by 73% in the first patient who received charcoal hemoperfusion and by 55% in the second patient who received high-flux hemodialysis. Conclusions: In presenting these cases, we aimed to show the decrease of CBZ serum levels by using two different hemodialysis modalities in CBZ intoxication.

Carbamazepine intoxication complicated by status epilepticus and ventricular fibrillation in the youth ; a case report

Carbamazepine intoxication complicated by status epilepticus and ventricular fibrillation in the youth ; a case report

A Child with Coma, Hypotension, Respiratory Depression and Cardiac Conduction Disturbance - Carbamazepine Poisoning

Previously healthy child presenting with coma, hypotension and respiratory depression is challenge to the treating clinician. The wide availability of anticonvulsants increases the risk of overdose, may be intentional or accidental. Adequate history taking is very important to clinch the diagnosis. The clinical spectrum of carbamazepine poisoning may range from drowsiness to profound coma with respiratory failure. Cardiotoxicity is rare, presents primarily as conduction disturbances. Here with we report a 14 year old boy who presented with coma, respiratory depression, hypotension and cardiac involvement. The diagnosis of carbamazepine toxicity was revealed only after adequate history taking and toxicology screening.

Early hemoperfusion for emergency treatment of carbamazepine poisoning

ObjectivesTo investigate the clinical value of early hemoperfusion (HP) in emergency treatment of carbamazepine (CBZ) poisoning. Methods104 patients with acute CBZ poisoning treated from August 2004 to October 2015 in the Emergency Department were reviewed. Patients were categorized into three groups: group A, who received HP treatment in the Emergency Department; group B, who received HP treatment in the blood purification room; and group C, who did not received HP treatment. Pharmacokinetic parameters of CBZ and remission of complications were compared among the three groups. ResultsBoth groups A and B had lower time to peak, area under curve and maximum concentration values than group C (P<0.05), and these kinetics indexes were significantly lower in group A than in group B (P<0.05). The mean retention times were 0.85±0.08, 1.20±0.15 and 2.52±0.29days in the three groups, respectively, and were significantly lower value in group A than in group B (P<0.05). The incidences of respiratory depression and seizure in group A were significantly lower than those of groups B and C (P<0.05). Group A had significantly higher Glasgow coma scale (GCS) scores at 4h after admission than the other two groups (P<0.05), and group B had significantly higher GCS scores than group C at 6h after admission (P<0.05). ConclusionsInitiation of HP in the early treatment stage of CBZ poisoning upon admission to an emergency department can significantly reduce the plasma concentration and retention period of CBZ, relieve the symptoms and shorten the overall treatment period.

Retrospective Analysis of Anticonvulsant Exposures Admitted to Department of Emergency Medicine in Dokuz Eylül University Hospital

Purpose: To evaluate demographic characteristics, clinical signs and symptoms, treatment methods and clinical outcomes of anticonvulsant exposures in cases who were admitted to the Department of Emergency Medicine of in Dokuz Eylul University Hospital DEUH between 2000 and 2010 and reported to the Dokuz Eylul University Drug and Poison Information Center DEUDPIC .Methods: Age, sex, type of the anticonvulsant agents, route and causes of the exposure, clinical signs and symptoms, recommended and applied treatment methods and outcomes were recorded on a standard data forms, then entered into a computerized database program Ruber . The chi-square test was used in the statistical analyses. Results: Seventy seven patients 45 women, 32 men whose data were fully accessible were studied. Exposures were found to mostly occur due to acute 50.6% and intentional 77.9% . Patients presenting with anticonvulsant exposure, were most commonly admitted 32.5% to the DEUH within two hours after the ingestion. The most common causes of poisoning were identified as carbamazepine 32.5% and valproic acid 23.4% . On clinical evaluation, 36.4% of the patients did not develop any clinical signs or symptoms, and 7.8% of the patients developed severe clinical signs and symptoms. Most of the severe cases 66.7% resulted from carbamazepine ingestion. Also, 88.3% of the cases were found to have recovered and were discharged from the hospital without sequelae, no death occurred. The mean length of stay was 19.6±25.6 hours.Conclusion: Carbamazepine intoxication ranked first among the intoxications due to anticonvulsant exposures. In this case, the length of follow up in the emergency department may be prolonged, particularly as a result of the anticholinergic effects of carbamazepine that may delay the onset of clinical manifestations

Toxicology monitoring in carbamazepine poisoning. The effects of multiple dose activated charcoal

Toxicology monitoring in carbamazepine poisoning. The effects of multiple dose activated charcoal

Clinical management of carbamazepine intoxication during anti-tubercular treatment: a case report

We describe a 67-year-old man with medical history of focal post-stroke seizure and type 2 diabetes mellitus treated with carbamazepine, clobazam, gliclazide, insulin glargine, and omeprazole we visited for the onset in the last 7 days of asthenia, cough with mucus, breathing difficulty, chest pain, and weight loss. After clinical and laboratory tests, pulmonary tuberculosis was diagnosed, and a treatment with isoniazid, ethambutol, pyrazinamide rifampicin, and pyridoxine was started. Therapeutic drug monitoring of tuberculosis treatment documented that all drugs were in normal therapeutic range. Four days after the beginning of the treatment, we documented the improvement of fever, and three days later the patient showed sleepiness, visual disorder and asthenia. Clinical and pharmacological evaluation suggested a carbamazepine toxicity probably related to a drug interaction (Drug Interaction Probability Scale score = 6). The impossibility to switch carbamazepine for another antiepileptic drug, due to a resistant form of seizure, induced the discontinuation of tuberculosis treatment, resulting in the normalization of serum carbamazepine levels in one day (10 µg/ml) and in the worsening of fever, requiring a new clinical and pharmacological evaluation. The titration dosage of carbamazepine and its therapeutic drug monitoring allowed to continue the treatment with both antitubercular drugs and carbamazepine, without the development of adverse drug reactions. To date, tuberculosis treatment was stopped and clinical evaluation, radiology and microbiology assays documented the absence of tubercular infection and no seizures appeared (carbamazepine dosage 800 mg/bid; serum levels 9.5 µg/ml).

Risk factors and the outcome of therapy in patients with seizure after Carbamazepine poisoning: A two-year cross-sectional study.

Objective:We aimed to investigate the frequency of seizure after acute carbamazepine poisoning and the important risk factors related to the outcomes of therapy.Methods:In this two-year cross-sectional study conducted in a University Hospital in Iran, 114 patients with acute carbamazepine poisoning were divided into two groups of with seizure (n = 8) and without seizure (n = 106) after intoxication. Demographic data, average amount of drug ingestion, time elapsed from ingestion to hospital admission, history of seizure before poisoning, mental status, visual disturbances and nystagmus, duration of hospitalization, the outcomes of therapy, arterial blood gas values and serum biochemical indices were compared between the two groups.Findings:Patients with seizure had an estimated (Mean ± SD) ingestion of 14,300 ± 570 mg carbamazepine, which was significantly higher (P < 0.0001) than the seizure-free group (4600 ± 420 mg). The estimated average time between drug ingestion and hospital admission in patients with seizure and the seizure-free group were 515 ± 275 and 370 ± 46 minutes, respectively (P < 0.0001). In this study, 104 out of the total number of patients had recovered without any complication. Need for respiratory support, including airway support or intubation were the most recorded complication. One patient died after status epilepticus and aspiration pneumonia.Conclusion:The ingested amount of carbamazepine and the time elapsed from the ingestion of drug to hospital admission may influence the occurrence of seizure after acute carbamazepine poisoning; however, the outcome of supportive care in these patients seems to be positive.

Severe carbamazepine intoxication unresponsive to albumin‐enhanced continuous venovenous hemodiafiltration with low dialysate flow

Carbamazepine (CBZ) intoxication can be associated with severe toxicity, including neurological and cardio-respiratory abnormalities. Highly protein-bound, CBZ is not removed efficiently through conventional hemodialysis. Charcoal hemoperfusion is the most effective extracorporeal elimination therapy for CBZ intoxication. Recent reports have indicated that continuous venovenous hemodiafiltration (CVVHDF), albumin-enhanced continuous venovenous hemodialysis, high-flux hemodialysis and plasma exchange can be as effective as charcoal hemoperfusion. In contrast to recent reports, which demonstrated the effectiveness of CVVHDF with high dialysate flow in CBZ intoxication, we observed that serum CBZ level was decreased minimally by albumin-enhanced CVVHDF with low dialysate flow. Therefore, albumin-enhanced CVVHDF with high dialysate flow should be considered in severe CBZ intoxication, if hemoperfusion is unavailable because of the lack of facilities or if it cannot be performed.

Remitting-Relapsing Carbamazepine Overdosage Mimicking Vertebrobasilar Transient Ischemic Attacks

The objective of this article is to describe an atypical, remitting-relapsing presentation of carbamazepine toxicity due to its interaction with nebivolol. The method we use is a case report of an elderly epileptic patient in treatment with antiepileptic drugs (AEDs) and antihypertensive drugs, manifesting transient neurological symptoms in association with high blood pressure values. The case report is of a 72-year-old male by forty years of age had tonicclonic seizures related to the presence of a cerebral arteriovenous malformation. Seizures had been successfully controlled for many years by the same dosage of carbamazepine and lamotrigine, and recently total serum carbamazepine levels resulted within the “therapeutic range.” He had also a history of controlled essential hypertension, but lately he manifested a scarce control of his blood pressure values. Few days after a modification of his antihypertensive therapy, the patient had two transient episodes of dysarthria, ataxia, and dizziness. At the emergency department, his blood pressure values were 190/110 mmHg, ECG and routine blood tests were normal, and a brain CT did not show acute lesions; about two hours later, his neurological examination was normal. Morning fasting carbamazepine serum levels were “normal” too; therefore, his symptoms were initially interpreted as vertebrobasilar transient ischemic attacks. However, the recurrence of similar episodes despite the normalization of his blood pressure suggested a carbamazepine intoxication. Indeed, its dosage resulted too high just in occasion of one of his attacks. A moderate reduction of carbamazepine was followed by cessation of toxicity. This case reminds us to be aware of adverse consequences of other drugs in patients assuming carbamazepine: in this case, its toxicity was consequential to a likely metabolic interaction with nebivolol.

Plasma‐exchange treatment for severe carbamazepine intoxication: A case study

Acute poisoning is an important cause of morbidity and mortality during childhood. This manuscript reports the positive outcome of a pediatric case with a history of accidental carbamazepine intake treated using plasma exchange. A 3-year-old male presented with severe carbamazepine intoxication. He was comatose and had generalized tonic clonic seizure, ventricular tachycardia, and hypotension. Although he did not respond to classical therapies, we performed two sessions of plasma exchange. The patient recovered rapidly and was discharged from the hospital six days from the time of carbamazepine ingestion with no complication or neurologic impairment. Plasma exchange can be performed safely in very small children, and it might be the first line treatment, particularly for intoxication with drugs that have high plasma-protein-binding properties.