Successful treatment of excessive dose of carbamazepine

Abstract

Carbamazepine is used in the treatment of epilepsy; it is also prescribed for treatment of neuralgic pain syndromes and certain affective disorders. Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma, respiratory depression, arrhythmia, hemodynamic instability, and death. There is no specific antidote. Multiple-dose activated charcoal and hemodialysis are the main treatment for carbamazepine intoxication. In this paper, we report the case of a 19-year-old woman with excessive dose carbamazepin intoxication and our successful treatment with multiple-dose activated charcoal and hemodialysis.

Introduction

Carbamazepine is an anticonvulsant and mood-stabilizing drug used in the treatment of epilepsy, bipolar disorder, and neuralgic pain syndromes. It is a commonly prescribed anti-epileptic agent. The therapeutic dose is 15-25 mg/kg and required serum levels of carbamazepine are within 4-12 μg/ ml.[1] Carbamazepine causes cardiac conduction disorder and central nervous system depression.[2] The drug's relatively high molecular weight, elevated volume of distribution, and intense protein-binding render it difficult to extracorporeal removal, but published experience with hemoperfusion or hemodialysis show variable results.[3] In this paper, we report a 19-year-old woman with fatal-dose carbamazepin intoxication who was treated successfully with multiple-dose activated charcoal and hemodialysis.

Case Report

A 19-year-old woman was admitted to the emergency department with a suicide attempt with carbamazepine (total dose taken was 8000 mg – 186 mg/kg). This was the patient's third suicide attempt. Pupillary were isocoric and mydriatic, and deep tendon reflexes were bilaterally equal. There was no evidence of lateralization. Glasgow Coma Scale (GCS) was 7; blood pressure, 70/40 mm Hg; pulse rate, 112/min rhythmic; respiratory rate, 22/min; and body temperature, 36.1°C. Electrocardiography (ECG) showed normal sinus rhythm. Computerized tomography of the brain was normal. Isotonic fluid therapy was started early in the emergency department. Nasogastric catheter was attached for gastric lavage and activated charcoal was given. The patient was admitted to the intensive care unit. Isotonic fluid infusion and 50 g of activated charcoal was administered every 4 hours. The recorded laboratory parameters were the following: hemoglobin, 12.8 g/ dl; leukocyte, 14600/mm³; platelet, 278000/mm³; urea, 22 mg/dl; creatinine, 0.59 mg/ dl; sodium, 138 mmol/L; potassium, 4.5 mmol/L; calcium, 8.4 mg/dL; Aspartate Aminotransferase (AST), 13 U/L; Alanine Transaminase (ALT), 29 U/L; arterial blood pH, 7.27; pCO₂, 40; pO₂,140; and HCO₃, 18. A hemodialysis catheter was attached to the right femoral and two consecutive sessions of hemodialysis were performed. We measured the carbamazepin level in the serum by high-pressure liquid chromatography. Pre-hemodialysis serum levels of carbamazepine was 57.7 μg/ml (normal value, 4-10 μg/ml; toxic dose, >15 μg/ml) and serum level of carbamazepine after hemodialysis was 28.9 μg/ml. The patient was conscious on the third day with a GCS of 15; blood pressure, 110/70 mm Hg; pulse rate, 78/min; and respiratory rate, 14/min. Serum level of carbamazepine was 6.8 μg/ml. The patient was transferred to the psychiatric clinic on the fifth day, as she was having persistent suicidal thoughts.

Discussion

Carbamazepine intoxication is associated with serum level of carbamazepine.[1,2] The clinical findings are usually neurological. Ataxia, nystagmus, mydriasis, ophthalmoplegia, sinus tachycardia, atrioventricular block, convulsions, myoclonus, hyperthermia, coma, and respiratory arrest may also be seen.[2] In our case, loss of consciousness, nystagmus, mydriasis, sinus tachycardia, convulsions, coma, hypokalemia, and transient pancytopenia were detected.

Deaths due to carbamazepine intoxication have been reported. A 13% mortality was observed in the study of 307 patients with carbamazepine intoxication. A serum concentration of 40 μg/ml or more is usually fatal. Severe central nervous system depression is typical if oral dose is more than 50 mg/kg.[2,4–6] In our case, the oral dose was 186 mg/kg and serum level of carbamazepine was 57.7 μg/ml. Central nervous system depression continued for three days. Fluid therapy in the early period, activated charcoal and hemodialysis were administered for drug elimination. Hemodialysis were performed in two consecutive sessions because of the absence of carbon hemoperfusion. Serum levels of carbamazepine decreased after hemodialysis. It is reported that hemodialysis can be performed in the absence of carbon hemoperfusion as in our case.[7–10]

Because of high mortality of carbamazepine intoxication, fluid therapy and activated charcoal treatment must be started emergently and hemodialysis must be performed even in the absence of carbon hemoperfusion.