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Wang L, Wang Y, Zhang RY, Wang Y, Liang W, Li TG. Management of acute carbamazepine poisoning: A narrative review. World J Psychiatry 2023; 13:816-830. [DOI: 10.5498/wjp.v13.i11.816] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 09/23/2023] [Accepted: 10/11/2023] [Indexed: 11/17/2023] Open
Abstract
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.
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Affiliation(s)
- Luan Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yang Wang
- Department of General Surgery, The 4th Affiliated Hospital of China Medical University, Shenyang 110032, Liaoning Province, China
| | - Ruo-Ying Zhang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yao Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Wei Liang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Tie-Gang Li
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Manto MU. Cerebellotoxic Agents. HANDBOOK OF THE CEREBELLUM AND CEREBELLAR DISORDERS 2022:2363-2408. [DOI: 10.1007/978-3-030-23810-0_96] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Manto MU. Cerebellotoxic Agents. HANDBOOK OF THE CEREBELLUM AND CEREBELLAR DISORDERS 2021:1-46. [DOI: 10.1007/978-3-319-97911-3_96-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 12/15/2020] [Indexed: 09/02/2023]
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Ghannoum M, Yates C, Galvao TF, Sowinski KM, Vo THV, Coogan A, Gosselin S, Lavergne V, Nolin TD, Hoffman RS. Extracorporeal treatment for carbamazepine poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2014; 52:993-1004. [PMID: 25355482 PMCID: PMC4782683 DOI: 10.3109/15563650.2014.973572] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Context. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence and consensus-based recommendations on the use of extracorporeal treatments (ECTRs) in poisoning. Objectives. To perform a systematic review and provide clinical recommendations for ECTR in carbamazepine poisoning. Methods. After a systematic literature search, the subgroup extracted the data and summarized the findings following a pre-determined format. The entire workgroup voted via a two-round modified Delphi method to reach a consensus on voting statements, using a RAND/UCLA Appropriateness Method to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote determined the final recommendations. Results. Seventy-four articles met inclusion criteria. Articles included case reports, case series, descriptive cohorts, pharmacokinetic studies, and in-vitro studies; two poor-quality observational studies were identified, yielding a very low quality of evidence for all recommendations. Data on 173 patients, including 6 fatalities, were reviewed. The workgroup concluded that carbamazepine is moderately dialyzable and made the following recommendations: ECTR is suggested in severe carbamazepine poisoning (2D). ECTR is recommended if multiple seizures occur and are refractory to treatment (1D), or if life-threatening dysrhythmias occur (1D). ECTR is suggested if prolonged coma or respiratory depression requiring mechanical ventilation are present (2D) or if significant toxicity persists, particularly when carbamazepine concentrations rise or remain elevated, despite using multiple-dose activated charcoal (MDAC) and supportive measures (2D). ECTR should be continued until clinical improvement is apparent (1D) or the serum carbamazepine concentration is below 10 mg/L (42 the μ in μmol/L looks weird.) (2D). Intermittent hemodialysis is the preferred ECTR (1D), but both intermittent hemoperfusion (1D) or continuous renal replacement therapies (3D) are alternatives if hemodialysis is not available. MDAC therapy should be continued during ECTR (1D). Conclusion. Despite the low quality of the available clinical evidence and the high protein binding capacity of carbamazepine, the workgroup suggested extracorporeal removal in cases of severe carbamazepine poisoning.
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Affiliation(s)
- Marc Ghannoum
- Division of Nephrology, Verdun Hospital, University of Montreal , Montreal, QC , Canada
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Manto M. Cerebellotoxic Agents. HANDBOOK OF THE CEREBELLUM AND CEREBELLAR DISORDERS 2013:2079-2117. [DOI: 10.1007/978-94-007-1333-8_96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Benini R, Ben Amor IM, Shevell MI. Clinical clues to differentiating inherited and noninherited etiologies of childhood ataxias. J Pediatr 2012; 160:152-7. [PMID: 21840535 DOI: 10.1016/j.jpeds.2011.06.029] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Revised: 04/18/2011] [Accepted: 06/22/2011] [Indexed: 10/17/2022]
Abstract
OBJECTIVE To identify clinical features at presentation that differentiate inherited and noninherited etiologies of childhood ataxias. STUDY DESIGN A retrospective chart review analysis was conducted on 167 patients evaluated in neurology outpatient clinics for ataxia or ataxia-related symptoms. The frequency of clinical features, determined a priori, in the 2 groups was compared. RESULTS A larger proportion of patients were diagnosed with a nongenetic cause than with a genetic cause (89% [148 patients] vs 11% [19 patients]). The majority of patients in the nongenetic group (56% [83/148]) presented early for medical evaluation, compared with 31% (6/19) in the genetic group. Consanguinity (16% vs 4%) and positive family history (16% vs 2%) were more frequent in the genetic group. Presenting symptoms of abnormal gait (95% vs 57%) and muscle weakness (47% vs 8%), including physical findings of abnormal muscle tone (63% vs 32%), abnormal reflexes (63% vs 16%), clonus (26% vs 9%), dysmetria (32% vs 5%), pes cavus (21% vs 1%), sensory deficits (16% vs 0%), and nonneurologic musculoskeletal abnormalities (58% vs 19%), were more prevalent in the genetic group. CONCLUSION Certain clinical features can help delineate between inherited and noninherited causes of childhood ataxia and thus guide physicians in the targeted evaluation of patients.
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Affiliation(s)
- Ruba Benini
- Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada
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7
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Abstract
The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening.
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Affiliation(s)
- Mario Manto
- Unité d'Etude du Mouvement, FNRS Neurologie, ULB Erasme, Brussels, Belgium.
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Unei H, Ikeda H, Murakami T, Tanigawa K, Kihira K. Detoxication treatment for carbamazepine and lithium overdose. YAKUGAKU ZASSHI 2008; 128:165-70. [PMID: 18176069 DOI: 10.1248/yakushi.128.165] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.
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Affiliation(s)
- Hiroko Unei
- Department of Pharmaceutical Services, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
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Clinical experience with carbamazepine overdose: relationship between serum concentration and neurological severity. J Clin Psychopharmacol 2008; 28:241-3. [PMID: 18344740 DOI: 10.1097/jcp.0b013e3181674608] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Affiliation(s)
- Marc J Dinkin
- Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA
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Yildiz TS, Toprak DG, Arisoy ES, Solak M, Toker K. Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine overdose in a pediatric patient. Paediatr Anaesth 2006; 16:1176-8. [PMID: 17040307 DOI: 10.1111/j.1460-9592.2006.01955.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Carbamazepine (CBZ) intoxication is an important issue in acute poisoning practice. Highly protein-bound, CBZ is not removed efficiently through conventional hemodialysis. We describe the use of continuous venovenous hemodiafiltration (CVVHDF) in a 2-year-old boy who developed general tonic clonic seizure and respiratory depression due to controlled-release formula of CBZ overdose (peak drug level of > 20 microg.ml(-1), therapeutic range: 5-10 microg.ml(-1)). Serum CBZ concentrations fell to 0.25 microg.ml(-1) at the end of hemodiafiltration. The patient recovered rapidly and was discharged from hospital 4 days from the time of ingestion with no complications or neurologic impairment.
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Affiliation(s)
- Tulay Sahin Yildiz
- Department of Anaesthesiology, School of Medicine, University of Kocaeli, Kocaeli, Turkey.
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Affiliation(s)
- H A Spiller
- Kentucky Regional Poison Center, Louisville, Kentucky 40232-5070, USA.
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Schuerer DJ, Brophy PD, Maxvold NJ, Kudelka T, Bunchman TE. High-efficiency dialysis for carbamazepine overdose. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 2000; 38:321-3. [PMID: 10866333 DOI: 10.1081/clt-100100938] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND Carbamazepine intoxication is associated with seizures, coma, arrhythmias, and death. In acute intoxications, charcoal hemoperfusion enhances removal of the drug but is associated with thrombocytopenia, coagulopathy, hypothermia, and hypocalcemia. Alternatively, high-efficiency hemodialysis can be used without the side effects of charcoal hemoperfusion. CASE REPORT We report an 18-month-old comatose, convulsing child with plasma carbamazepine 27 microg/mL treated with high efficiency hemodialysis. Therapeutic carbamazepine levels were obtained after 4.5 hours of high-efficiency hemodialysis. The patient developed no untoward side effects, improved clinically, and was subsequently discharged home without sequelae. We conclude that high-efficiency hemodialysis is a safe, effective alternative to charcoal hemoperfusion in the pediatric population.
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Affiliation(s)
- D J Schuerer
- C.S. Mott Children's Hospital, University of Michigan, Ann Arbor 48109, USA
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Matos ME, Burns MM, Shannon MW. False-positive tricyclic antidepressant drug screen results leading to the diagnosis of carbamazepine intoxication. Pediatrics 2000; 105:E66. [PMID: 10799630 DOI: 10.1542/peds.105.5.e66] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Ingestion of toxic substances is a common problem in pediatrics. When presented with the limited history of an unknown ingestion in a patient with altered mental status, a clinician depends on the physical examination and a toxic screen to determine the ingested substance(s). Some toxic screens yield false-positive or false-negative results that confound identification of ingested toxins. Three cases are presented in which carbamazepine ingestions were identified because of the false-positive tricyclic antidepressant serum toxic screen result in each case. Carbamazepine ingestion is one of the most common pediatric overdoses. Side effects include altered mental status, tachycardia, mydriasis, seizures, coma, and death. Several other substances also cause false-positive tricyclic antidepressant toxic screen results, including certain antipsychotic medications, antihistamines, and the muscle relaxant cyclobenzaprine. Specific tests and drugs causing false-positive results are presented in table form. More modern methods, specifically gas chromatographic-mass spectrometric, are more reliable in distinguishing these drugs. Knowledge of which substances commonly cause false-positive results on a given toxic screen can still lead the clinician to the correct diagnosis. tricyclic, carbamazepine, ingestion, intoxication, drug screen.
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Affiliation(s)
- M E Matos
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
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Reacciones adversas de la carbamacepina. A propósito de un caso. Semergen 2000. [DOI: 10.1016/s1138-3593(00)73601-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Abstract
Carbamazepine is used to manage generalized tonic-clonic, partial, and mixed partial and generalized seizure disorders in children. It is frequently associated with neurologic adverse events, Stevens-Johnson syndrome, and hematologic side effects. Hepatic and renal adverse effects are less common but can cause death. A 6-year-old boy receiving carbamazepine for partial seizure disorder developed hepatorenal failure. With discontinuation of the drug, his liver and kidney function returned to normal within 2 weeks.
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Affiliation(s)
- M R Haase
- Department of Pediatric Pharmacy Practice, Medical University of South Carolina, Charleston, USA
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Abstract
PURPOSE Although the paradoxical ability of antiepileptic drugs (AEDs) to increase seizure activity has been recognized for decades, the underlying mechanisms are poorly understood and few systematic studies have addressed this problem. This article is intended to provide a critical review of available literature on this topic. METHODS Information was collected by means of computerized literature searches, screening of journals and textbooks, and consultation with colleagues. Mechanisms which potentially might precipitate underlying drug-induced exacerbation of seizures were considered based on available pharmacologic and clinical knowledge. RESULTS The reviewed information suggests that a paradoxical increase in seizure frequency may occur as a result of at least two separate mechanisms. The first appears to involve a nonspecific manifestation of drug intoxication; seizure-worsening in this context is usually reversible by dosage reduction or elimination of unnecessary polypharmacy. Conversely, the other mechanism may involve a distinct adverse primary action of the drug in specific seizure types or in syndromic forms. Carabamazepine, in particular, has been reported to precipitate or exacerbate a variety of seizures, most notably absence, atonic, or myoclonic seizures in patients with generalized epilepsies characterized by bursts of diffuse and bilaterally synchronous spike-and-wave EEG activity. Phenytoin and vigabatrin also have been implicated in worsening of seizures, particularly generalized seizures, whereas gabapentin has been associated repeatedly with precipitation of myoclonic jerks. Benzodiazepines occasionally have been reported to precipitate tonic seizures, especially when given intravenously to control other seizure types in patients with Lennox-Gastaut syndrome. Seizure deterioration has been reported also with other drugs; though in most cases evidence is still insufficient for meaningful conclusions to be drawn. CONCLUSIONS Drug-induced exacerbation of seizures is a serious and common clinical problem that is often unrecognized or overlooked by the treating physician. Its occurrence appears to be related to three possible causes: an incorrect diagnosis of seizure type or syndromic form, lack of knowledge about certain drugs that are contraindicated in specific types of epilepsies, or to prescription of excessive drug dosages and drug combinations. Further studies are required to evaluate the prevalence of this phenomenon of drug-induced exacerbation of seizures, to investigate its mechanisms in greater detail and to characterize additional prognostic factors that may be used for early identification of patients at risk.
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Affiliation(s)
- E Perucca
- Clinical Pharmacology Unit, University of Pavia, Italy
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Montgomery VL, Richman BJ, Goldsmith LJ, Rodgers GC. Severity and carbamazepine level at time of initial poison center contact correlate with outcome in carbamazepine poisoning. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 1995; 33:311-23. [PMID: 7629897 DOI: 10.3109/15563659509028916] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
We reviewed data from carbamazepine poisonings reported to the Kentucky Regional Poison Center from January 1986 through March 1992 to identify information available at the time of poison center contact which correlates to outcome. The Spearman rank correlation test was used to describe the relationship between two ordinal variables and interval-level variables. The Kruskal-Wallis test was used to determine the relationship between categorical and ordinal variables. Two way analysis of variance was used to test the effect of routine carbamazepine use on final severity and carbamazepine level of 345 reports involving carbamazepine poisoning; 263 (76%) involved only carbamazepine ingestion and formed the database. One hundred eighty four (70%) carbamazepine ingestions occurred in victims < or = 17 years old, 79 (30%) occurred in adults. Severity assigned at the time of initial poison center contact was significantly correlated with outcome severity for children and adults (r > or = 0.9, p < 0.00001). The amount reported ingested influenced the correlation between initial and final severity; whereas, time elapsed between ingestion and poison center contact did not alter the correlation between initial and final severity. The reason for ingestion was significantly correlated with outcome (p < 0.00001). A significant correlation between outcome and peak carbamazepine level for each age group was observed (pediatric r = 0.5, p < 0.00001, and adult r = 0.4, p = 0.008). Carbamazepine levels > 85 mumol/L (> 20 mcg/mL) were associated with more severe toxicity.
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Affiliation(s)
- V L Montgomery
- Department of Pediatrics, University of Louisville, KY 40292, USA
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