Carbamazepine-induced hyperglycemia: A rare case report.

Carbamazepine is a commonly used iminostilbene antiepileptic medication and it is estimated that 46.9% of the total antiepileptic drug overdose in the United Kingdom is because of this drug. The overdose of Carbamazepine can show negative effects on multiple systems, these include neurologic (ataxia, seizures, and altered sensorium), cardiac (tachycardia, hypotension) and metabolic manifestations. We reported a case of a 17-year-old girl had an increase in glucose levels after voluntary ingestion carbamazepine tablets. After ingestion, her gross random blood sugar level was increased, then physician suspected that she might be a Type I diabetic,but HbA1C[glycosylated hemoglobin] levels was found normal.Carbamazepine was discontinued and patient received symptomatic therapy. The patient had decreased levels of blood sugar level,after removal of the drug within the next day after ingestion of carbamazepine. A Naranjo assessment was obtained, indicating a definite relationship between the patient's increased in blood glucose levels and her use of carbamazepine.

First aid interventions by laypeople for acute oral poisoning.

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.

[From carbonmonoxide intoxication to organ donation; organ protective mechanic ventilation in severe pulmonary damage]. / Karbonmonoksit intoksikasyonundan organ donasyonuna; agir pulmoner hasarda organ koruyucu mekanik ventilasyon.

Organ donation is a matter of concern in critically ill patients who need intensive care after carbonmonoxide (CO) intoxication. A 26-year-old female patient was unconscious after having spent 20 minutes in the bathroom with a water heater (70% butane and 30% propane mixture). In the CT of the patient with Glasgow Coma Scale (GCS) 3, ventricular system was erased, white-gray matter separation was lost and fissures were observed as erased. Torax CT showed conspicuous areas showing air bronchograms in both lung bases and posterior areas and diffuse frosted glass densities in other areas. In a patient with no improvement in consciousness; apnea test, neurological examination and CT angiography showed that there was no blood flow in the brain and brain death was confirmed. On the second day of hospitalization, the relatives gave their approval for the donation. It may also be advantageous to use oxygen at high concentrations in carbonmonoxide poisoning as it may allow recruitment of closed alveoli. Successful kidney, heart, lung, liver and pancreas transplants from donors exposed to CO have been reported. Carbonmonoxide intoxication may be appropriate for transplantation for patients who are waiting for organs of brain death cases where the organ preservation is well done. Although carbonmonoxide intoxication has failed in the literature, it shows that there is no definite contraindication.

Early hemoperfusion for emergency treatment of carbamazepine poisoning.

OBJECTIVES: To investigate the clinical value of early hemoperfusion (HP) in emergency treatment of carbamazepine (CBZ) poisoning. METHODS: 104 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. RESULTS: Both 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). CONCLUSIONS: Initiation 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.

A case of severe carbamazepine overdose treated successfully with combined hemoperfusion and hemodialysis technique.

Carbamazepine intoxication manifests as altered mental status ranging from drowsiness to a coma and/or cardiac abnormalities such as sinus tachycardia, prolongation of the QRS interval, ventricular tachycardia, and hypotension. The patient may be agitated, but central nervous system (CNS) depression and presentation with coma is more common and could be lethal. Serious CNS toxicity often requires hemoperfusion and/or hemodialysis (HD). Herein, we present a case of a comatose patient, who was treated with a combination of hemoperfusion and HD in series. Our approach to treat the patient with a combination of hemoperfusion and HD was based on evidence from the literature supporting that the hemoperfusion and HD in series might provide the best clearance of carbamazepine.

Combination Clearance Therapy and Barbiturate Coma for Severe Carbamazepine Overdose.

A 15-year-old female subject presented comatose, in respiratory failure and shock, after the intentional ingestion of ∼280 extended-release 200-mg carbamazepine tablets with a peak serum concentration of 138 µg/mL (583.74 µmol/L). The patient developed clinical seizures and an EEG pattern of stimulus-induced rhythmic, periodic, or ictal discharges, suggestive of significant cortical dysfunction. Due to the extremely high drug serum concentration and clinical instability, a combination of therapies was used, including lipid emulsion therapy, plasmapheresis, hemodialysis, continuous venovenous hemodiafiltration, and endoscopic intestinal decontamination. The patient's elevated serum lactate level with a high mixed venous saturation suggested possible mitochondrial dysfunction, prompting treatment with barbiturate coma to reduce cerebral metabolic demand. The serum carbamazepine concentration declined steadily, with resolution of lactic acidosis, no long-term end-organ damage, and return to baseline neurologic function. The patient was eventually discharged in her usual state of health. In the laboratory, we demonstrated in vitro that the active metabolite of carbamazepine hyperpolarized the mitochondrial membrane potential, supporting the hypothesis that the drug caused mitochondrial dysfunction. We thus successfully treated a life-threatening carbamazepine overdose with a combination of modalities. Future studies are required to validate this aggressive approach. The occurrence of mitochondrial dysfunction must be confirmed in patients with carbamazepine toxicity and the need to treat it validated.

Severe Carbamazepine Intoxication in Children: Analysis of a 40-Case Series.

BACKGROUND We compared the factors that might impact the severity and the prognosis of carbamazepine (CBZ) intoxication in children, as well as the efficacy levels of the treatment options. MATERIAL AND METHODS Demographic information and clinical and laboratory findings for 40 patients were evaluated retrospectively. Predictive parameters for the development of serious complications were studied. RESULTS Median age of patients was 14 years; 65% of the patients were female. The most common pathological clinical finding and laboratory abnormality were inability to awaken the patient and hyperglycemia (45% and 60%, respectively). The incidences of convulsion, coma, and respiratory failure were 14 (35%), 10 (25%), and 3 (7.5%), respectively. The Glasgow Coma Scale (GCS) scores and pH levels at emergency service admission were significantly lower in the severe intoxication group and the ICU admission group, and body temperature and serum glucose and lactate levels were significantly higher in these groups. A significantly negative correlation was found between the serum CBZ level and the GCS score, but the serum CBZ level was found to be significantly positively correlated with the lactate level. CONCLUSIONS According to our study, the GCS score at admission to hospital, the serum CBZ, glucose, pH, and lactate levels, and body temperature might be useful in predicting serious CBZ intoxication and prognosis in pediatric cases. We conclude that invasive treatment methods, such as hemodialysis or albumin-enhanced continuous venovenous hemodialysis, should be used in patients who do not respond to supportive treatment.

Psychoactive pharmaceuticals at environmental concentrations induce in vitro gene expression associated with neurological disorders.

BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations. Preliminary studies in our laboratory identified gene sets associated with neuronal systems and human neurological disorders that were significantly enriched after treating fish brains with psychoactive pharmaceuticals at environmental concentrations. These gene expression inductions were associated with changes in fish behavior. Here, we tested the hypothesis that similar treatments would alter in vitro gene expression associated with neurological disorders (including autism) in human neuronal cells. We differentiated and treated human SK-N-SH neuroblastoma cells with a mixture (fluoxetine, carbamazepine and venlafaxine) and valproate (used as a positive control to induce autism-associated profiles), followed by transcriptome analysis with RNA-Seq approach. RESULTS: We found that psychoactive pharmaceuticals and valproate significantly altered neuronal gene sets associated with human neurological disorders (including autism-associated sets). Moreover, we observed that altered expression profiles in human cells were similar to gene expression profiles previously identified in fish brains. CONCLUSIONS: Psychoactive pharmaceuticals at environmental concentrations altered in vitro gene expression profiles of neuronal growth, development and regulation. These expression patterns were associated with potential neurological disorders including autism, suggested psychoactive pharmaceuticals at environmental concentrations might mimic, aggravate, or induce neurological disorders.

Carbamazepine and carbamazepine-10,11-epoxide clearance measurements during continuous venovenous hemofiltration in a massive overdose.

INTRODUCTION: Carbamazepine (CBZ) overdose can result in significant neurologic and cardiovascular toxicity, and is compounded by the presence of an active metabolite, carbamazepine-10,11-epoxide (CBZE). Existing publications describing continuous venovenous hemofiltration (CVVH) in CBZ overdose are limited in their ability to calculate accurate clearances. We report a case of CBZ overdose treated with CVVH with detailed measurement of CBZ, CBZE and their respective clearances calculated utilizing serial effluent measurements. This was coupled with serum level determinations comparing two analytical methodologies, time-of-flight mass spectroscopy and an immunoassay. CASE DETAILS: A 41-year-old woman presented unresponsive after an overdose of CBZ. Initial CBZ serum levels were markedly elevated (57.8 µg/mL) and continued to rise. Due to continued hemodynamic instability, extracorporeal removal was initiated using CVVH. MATERIALS AND METHODS: During the first 30 h of CVVH, interval serum samples and all ultrafiltrate bags were collected and analyzed. Serum and effluent levels of CBZ and CBZE were measured using an Agilent 6230 time-of-flight high-resolution mass spectrometer (TOF-MS). CBZ levels were also obtained utilizing the Microgenics CEDIA Carbamazepine Immunoassay (Thermo Fisher, Waltham, MA) for serum and effluent samples. Immunoassay analysis was performed using Siemens ADVIA 1800 instrument. RESULTS: The clearances achieved for CBZE (mean = 25.2, range 17.7-42.6 mL/min) exceeded that for CBZ (mean = 18.1, range 12.7-28.7 mL/min). CVVH removed a total of 1293 and 1261 mg of CBZ and CBZE, respectively. Serum levels of CBZ measured by immunoassay when compared with TOF-MS indicated cross reactivity of CBZE with the immunoassay. CONCLUSIONS: CVVH removed CBZE with higher clearances than CBZ. However, CVVH clearance rates for both CBZ and CBZE were lower than published clearances of CBZ and CBZE by intermittent hemodialysis. Our methodology allowed for a precise pharmacokinetic assessment of clearance based on total quantity of parent drug and active metabolite removed. Use of an immunoassay to determine CBZ serum levels reflects both parent compound and active metabolite due to cross-reactivity with CBZE.

Thirteen years of oxcarbazepine exposures reported to US poison centers: 2000 to 2012.

OBJECTIVES: Oxcarbazepine (OXC) is a 10-keto analogue of carbamazepine used in patients with partial and secondary generalized seizures. We evaluated ingestions of OXC reported to US poison centers for adverse effects from supratherapeutic doses and/or overdose. METHOD: Retrospective analysis of data reported to National Poison Data System from single-substance OXC ingestions between January 2000 and December 2012. RESULTS: There were 18,867cases with a mean of 1451 exposures/year. The patients were predominantly adults with 5464 exposures in children <6 years (29%). The most commonly reported clinical effects were drowsiness (n = 4703, 25%), vomiting (n = 1559, 8%), tachycardia (n = 590, 3%), agitated (n = 342, 1.8%), hypotension (n = 178, 0.9%), electrolyte disturbance (n = 153, 0.8%), coma (n = 156, 0.8%), and seizures (n = 121, 0.6%). There were 176 patients with a major effect of which 31 involved were children and 1728 (9%) patients with moderate effects of which 300 involved were children. Five deaths were reported in adults. Intentional exposure (e.g. suicide) was the reason for exposure in 68% of patients with major effects and in all fatalities. Fifty-three percent of adults and 38% of children were managed in a health-care facility (HCF). HCF utilization levels remained consistent. DISCUSSION: Severe outcomes appear to be infrequent (<1%). Unlike other anticonvulsants OXC does not appear to be proconvulsant in overdose. CONCLUSION: Serious outcomes for OXC overdoses are unlikely in the pediatric patient. With only mild symptoms likely, observation at home may be appropriate for the majority of cases. In the adult population there appears to be few neurologic and cardiovascular complications even in the intentional exposure.

[Successful hemodialysis for life-threatening carbamazepine drug overdose: Case-based introduction of new guidelines]. / Erfolgreiche Hämodialyse bei lebensbedrohlicher Carbamazepinintoxikation : Vorstellung neuer Leitlinien anhand eines Fallberichts.

BACKGROUND: Over the last decade, there has been a paradigm shift in the extracorporeal treatment of intoxications. The availability of new treatment options, especially new membranes has led to a decrease in the use of techniques like charcoal hemoperfusion, once considered the gold standard to eliminate highly protein bound substances. EXTRIP GUIDELINES: The EXtracorporeal Treatments In Poisoning (EXTRIP) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians, and nephrologists that is reviewing all available evidence in extracorporeal procedures for the treatment of poisonings in a standardized way to distill treatment recommendations for the physician at the bedside. One of the first available EXTRIP guidelines summarizes treatment recommendations for severe carbamazepine intoxications. CASE REPORT: We report the case of a 43-year-old Caucasian woman with who ingested about 21 g carbamazepine in a suicidal attempt together with alcohol. Combining gastroscopic removal of carbamazepine and multiple dose activated charcoal with intermittent high-flux hemodialysis lowered the initial carbamazepine level of 56.5 mg/l (47 mg/l before dialysis) to 25 mg/l. The patient, who initially required mechanical ventilation could be transferred to the psychiatric ward 24 h after ICU admission.

Carbamazepine poisoning treated by multiple extracorporeal treatments.

CONTEXT: Hemoperfusion (HP) or dialysis is occasionally used following carbamazepine (CBZ) toxicity but it remains unclear which is the most efficient modality. We describe a case of severe CBZ intoxication treated with different extracorporeal modalities during which CBZ toxicokinetics were compared. CASE DETAILS: A 58-year-old man was transferred to our facility 24 hours after ingesting over 14 g of sustained-release CBZ. Because of worsening neurological condition requiring mechanical ventilation and CBZ levels reaching 47.6 µg/mL, he underwent three intermittent hemodialysis (IHD), two continuous veno-venous hemofiltration (CVVH), and one IHD with HP (IHD-HP). IHD and CVVH removed 1.73 g of carbamazepine over 43 hours. Mean apparent half-life was 8.8 hours during IHD 49.1 hours during CVVH, and 5.1 hours during IHD-HP, while measured endogenous half-life after extracorporeal therapies was 81.4 hours. Mean CBZ clearances were 106.2 mL/min during IHD and 21.2 mL/ min during CVVH. His neurological status improved during extracorporeal elimination, and he was discharged without sequela after 16 days. Treatments were well tolerated aside from thrombocytopenia during IHDHP. DISCUSSION: All extracorporeal treatments facilitated CBZ elimination, although CVVH was significantly less efficient than IHD and IHD-HP. IHD-HP may be better than IHD alone but must be weighed against its risks. IHD appears sufficient to eliminate CBZ and may need to be repeated or prolonged according to the clinical context if CBZ absorption is delayed.

Características clínico-epidemiológicas de la intoxicación exógena grave en niños / Clinical and epidemiological characteristics of severe exogenous poisoning in children

Se realiza un estudio con el objetivo de caracterizar desde el punto de vista clínico y epidemiológico a los niños ingresados del Hospital General Docente Octavio de la Concepción y de la Pedraja del municipio Baracoa, con diagnóstico de intoxicación exógena aguda grave, desde el año 2011 al 2012. El universo está constituido por 34 niños. Se concluye que predominaron los niños mayores de 15 años, del sexo femenino, con inestabilidad emocional de la familia, intoxicados principalmente de forma no accidental, con drogas de abuso por vía oral, siendo la de mayor incidencia la carbamazepina que le produjeron fundamentalmente alteraciones del nivel de conciencia y fueron desintoxicados mediante el lavado gástrico, que no necesitaron ventilación mecánica, con estadía hospitalaria de 4 a 6 días, que ingresaron en estado grave y predominando los vivos al alta. Se recomienda realizar estudios de intervención comunitaria con los padres sobre la importancia de la comunicación con sus hijos y como mejorar la funcionabilidad familiar(AU)

A study is performed for characterizing from the standpoint of clinical and epidemiological situation of children admitted at the General Teaching Hospital Octavio de la Concepción y la Pedraja Baracoa, diagnosed with severe acute exogenous intoxication since 2011 to 2012. The universe consists of 34 children. As a conclusion in the research predominated children over 15 years old, female, with family emotional instability, intoxicated mostly not accident, abuse drugs orally, with the highest incidence carbamazepine ,mainly produced alterations level of consciousness and were detoxified by gastric lavage, who required mechanical ventilation with hospital stay of 4-6 days admitted in serious condition and predominantly live at discharge. It is recommended that community intervention studies are made with parents about the importance of Communications with their children and to improve the familiar functionality(AU)

Hypoglycemia - a rare complication of carbamazepine overdose.

Carbamazepine overdose usually presents with neurological manifestations such as ataxia, seizures and altered sensorium or cardiac manifestations that include tachycardia, hypotension and ventricular extra-systoles. We report a patient with carbamazepine overdose who manifested recurrent hypoglycemia on the third and fourth day following ingestion that resolved with supportive therapy.

Overdose with antiepileptic drugs: the efficacy of extracorporeal removal techniques.

Drug overdose is a growing problem among adolescents. Clinical severity depends on the drug and ingested amount, which in some cases may be life-threatening. We present a clinical case of a previously healthy teenage girl who ingested 16.4 g of carbamazepine and 14.5 g of valproic acid. She presented with profound disturbance of consciousness and toxic levels of both drugs, raised in the first hours after the ingestion. She was successfully treated with charcoal haemoperfusion followed by continuous venovenous hemodiafiltration. Overdose with the two drugs separately is common, but there are no reports of intoxication by simultaneous ingestion. High levels of carbamazepine and valproic acid can lead to severe systemic effects and management is made difficult by the absence of specific antidotes. Extracorporeal removal techniques are a good therapeutic option in these cases as they enhance the clearance by reducing the half-life of both drugs thereby preventing serious complications.

Extracorporeal treatment for carbamazepine poisoning: systematic review and recommendations from the EXTRIP workgroup.

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.

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.