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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Carbamazepine is used to treat epilepsy&#44; neuropathic pain&#44; certain affective disorders and as a migraine prophylactic drug&#46; Carbamazepine poisoning&#44; resulting from attempted suicide&#44; is a relatively common clinical problem which can result in coma&#44; hypoventilation&#44; arrhythmias&#44; haemodynamic instability and death&#46;<span class="elsevierStyleSup">1&#44;2</span> In the event of an overdose&#44; the drug&#8217;s relatively high molecular weight&#44; moderately large distribution volume and high protein-binding capacity makes it difficult to eliminate from the body&#46; For that reason&#44; published experiences using haemoperfusion or haemodialysis yielded highly variable results&#46;<span class="elsevierStyleSup">3-16</span> We describe a patient with acute carbamazepine poisoning who was successfully treated with prolonged haemoperfusion&#46; This case serves to illustrate that in cases of acute carbamazepine poisoning for which extracorporeal techniques are indicated&#44; prolonged haemoperfusion with activated charcoal is effective for quickly lowering circulating substance levels&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE REPORT</span></p><p class="elsevierStylePara">Female patient 27 years of age diagnosed with a personality disorder whose basic treatment consisted of 400 mg&#47;day carbamazepine&#44; 75mg&#47;day venlafaxine&#44; 5mg&#47;day lorazepam and 15mg&#47;day clorazepate dipotassium&#46; The patient was admitted due to a suicide attempt with an undetermined amount of carbamazepine&#46; The patient arrived at the emergency room approximately five hours after having ingested the drug&#46; She was conscious with a Glasgow score of 7 and showed mydriatic pupils&#44; mild drowsiness and disorientation&#46; 1&#44;500ml of isotonic saline solution and 1&#44;500ml of 5&#37; glucose solution were administered&#46;Arterial pressure was 123&#47;65mmHg&#44; heart rate was 90 beats&#47;min and diuresis progressed at 150-200ml&#47;hour&#46; Five hours after having ingested the drug and following several gastric lavages with activated charcoal&#44; carbamazepine plasma levels were at 31&#46;2&#181;g&#47;ml&#46; Other laboratory data were as follows&#58; haematocrit 37&#37;&#44; haemoglobin 13g&#47;dl&#44; leukocyte count 12&#44;800&#47;mm<span class="elsevierStyleSup">3</span>&#44; Platelet count 225&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#44; glucose 80mg&#47;dl&#44; urea 33mg&#47;dl&#44; creatinine 0&#46;96mg&#47;dl&#44; Na 138mmol&#47;l&#44; K 3&#46;6mmol&#47;l&#44; Cl 104mmol&#47;l&#44; bicarbonate 20&#46;8mmol&#47;l&#44; total calcium 8&#46;9mg&#47;dl&#44; total proteins 7&#46;5g&#47;dl&#44; GOT 18IU&#47;l&#44; GPT 37IU&#47;l&#44; prothrombin activity 110&#37;&#44; INR 0&#46;9&#46; Normal ECG&#46; The patient was moved to the Intensive Care Unit for monitoring&#44; and three hours after having been admitted&#44; began haemoperfusion treatment with a cartridge of activated charcoal &#40;Adsorba 300 C&#44; Gambro&#44; Hechingen&#44; Germany&#41; with a blood flow rate of 180ml&#47;min&#46; The pre-haemoperfusion carbamazepine level was 19&#46;5&#181;g&#47;ml&#46; In the five hours during which haemoperfusion was performed and afterwards&#44; the patient remained haemodynamically stable with a diuresis of 150ml&#47;h&#46; The post-haemoperfusion carbamazepine level was 7&#46;8&#181;g&#47;ml&#44; and eight hours later&#44; it was 3&#46;9&#181;g&#47;ml&#46; The patient was discharged 24 hours later for follow-up by the Psychiatric Unit&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHODS</span></p><p class="elsevierStylePara">Carbamazepine plasma levels were determined using a fluorescence polarisation immunoassay &#40;Abbott&#41;&#46; The analysed samples were obtained at time of admission&#44; pre- and post-haemoperfusion&#44; and several hours after completing the treatment&#46; The therapeutic range for carbamazepine is between 4 and 12&#181;g&#47;ml&#46; To determine the specific pharmacokinetic parameters&#44; we used carbamazepine plasma concentrations and employed standard equations to calculate the constant elimination rate &#40;K<span class="elsevierStyleInf">el</span>&#41; and the carbamazepine half-life &#40;T<span class="elsevierStyleInf">1&#47;2</span>&#41; before&#44; during and after haemoperfusion&#58; K<span class="elsevierStyleInf">el </span>&#40;h<span class="elsevierStyleSup">-1</span>&#41; &#61; 1&#47;time &#42; ln &#40;C1&#47;C2&#41;&#59; T<span class="elsevierStyleInf">1&#47;2</span> &#61; 0&#44;693&#47;K<span class="elsevierStyleInf">el</span>&#44; where &#8220;time&#8221; is the number of hours between carbamazepine concentrations C1 and C2&#46; The reduction rate &#40;RR&#41; was calculated using the following formula&#58; RR &#61; 100 x &#40;1-C2&#47;C1&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">Carbamazepine distribution and metabolism are complex processes&#46; Carbamazepine has a molecular weight of 236 Daltons&#46; After oral administration&#44; it is absorbed slowly &#40;70-95&#37;&#41;&#44; with a maximum plasma peak between 2 and 18 hours&#46; It binds tightly to proteins &#40;80-85&#37;&#41; and its distribution volume is 1-2L&#47;kg&#59; its elimination is fundamentally hepatic&#44; through the P450 &#40;CYP3A4&#41; cytochrome system&#44; and only 1-3&#37; is eliminated by the kidney&#46; The drug&#8217;s elimination half-life is between 12 and 20 hours&#44; but an overdose can last as long as 55 hours&#46;<span class="elsevierStyleSup">15</span></p><p class="elsevierStylePara">Carbamazepine poisoning can result in coma&#44; hypoventilation&#44; arrhythmias&#44; haemodynamic instability and death&#46; The mortality rate is as high as 13&#37; of all cases&#46;<span class="elsevierStyleSup">2</span> Keeping in mind the circulating level of carbamazepine&#44; poisoning can be classified in four stages&#58; potentially catastrophic relapse with levels &#60; 11&#181;g&#47;ml&#44; disorientation and ataxia at levels of 11-15&#181;g&#47;ml&#44; combativeness and hallucinations at levels of 15-25&#181;g&#47;ml and convulsions and coma at levels &#62; 25&#181;g&#47;ml&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Treatment for carbamazepine overdose has drawn on diverse extracorporeal elimination techniques such as haemoperfusion&#44; haemodialysis&#44; a combination of both&#44; continuous haemodiafiltration and even plasmapheresis&#46;<span class="elsevierStyleSup">3-21</span></p><p class="elsevierStylePara">However&#44; the most commonly used technique since the 1980s has been haemoperfusion with activated charcoal&#44; which reduces circulating carbamazepine levels in some poisoned patients by 25-50&#37; after 3-4 hours of treatment&#46;<span class="elsevierStyleSup">6-8</span> In other cases treated with haemodialysis using highly permeable membranes&#44; circulating carbamazepine levels decreased by 25-27&#37; in 3 to 4 hours&#46;<span class="elsevierStyleSup">10&#44;11</span> In a recent case that was treated with haemodialysis over four hours&#44; the carbamazepine level was reduced by more than 50&#37;&#46;<span class="elsevierStyleSup">9</span> In another study&#44; the combined use of haemodialysis and haemoperfusion resulted in a plasma level reduction of 50&#37;&#46;<span class="elsevierStyleSup">14</span> One theory to explain haemodialysis&#8217; paradoxical efficacy in eliminating the drug&#44; despite its tight protein binding&#44; suggests a high breakage rate of the drug&#8217;s union to proteins which would take place in countercurrent flows through the pores in the dialyser membrane&#46;<span class="elsevierStyleSup">13</span> In a few cases in which plasmapheresis was performed&#44; results were inconsistent&#46;<span class="elsevierStyleSup">19-21</span> Continuous albumin dialysis is another treatment option that resulted in an elimination T<span class="elsevierStyleInf">1&#47;2</span> of 4&#46;5 hours&#46;<span class="elsevierStyleSup">17</span> In turn&#44; when haemoperfusion with activated charcoal and high-flux haemofiltration was used&#44;&#160; the elimination T<span class="elsevierStyleInf">1&#47;2</span> varied between four and eight hours&#46; For all of these reasons&#44; it is evident that studies of larger patient groups are needed in order to evaluate the efficacy of different extrarenal purification techniques&#46; Other techniques such as MARS or Prometheus could also be useful&#46;</p><p class="elsevierStylePara">According to the initial carbamazepine levels&#44; our patient was in a severe state of intoxication&#46; The elapsed time since the patient ingested the drug &#40;about five hours&#41; permitted elimination of a certain amount of it by gastric lavage&#44; and probably also its adsorption to the activated charcoal administered through the nasogastric tube&#46; With five hours of haemoperfusion&#44; the carbamazepine plasma level dropped by 60&#37; and over the next eight hours&#44; using only forced diuresis&#44; levels remained within the therapeutic range with no rebound effect &#40;figure 1&#41;&#46; The anticipated T<span class="elsevierStyleInf">1&#47;2</span> of 20 hours was lowered to 3&#46;8 hours during haemoperfusion treatment &#40;table 1&#41;&#46; In this patient&#44; the carbamazepine T<span class="elsevierStyleInf">1&#47;2</span> was much lower than in previously published cases for which toxicokinetic studies were carried out&#46;<span class="elsevierStyleSup">6&#44;7</span> Therefore in this case&#44; haemoperfusion resulted in the extraction of a considerable amount of the circulating carbamazepine&#44; which was probably due to its long duration&#59; according to our estimates&#44; the cartridge became saturated after seven hours&#46;<span class="elsevierStyleSup">5</span> Following haemoperfusion&#44; when only endogenous elimination &#40;hepatic and renal&#41; was being used&#44; spontaneous clearance of carbamazepine resulted in an elimination T<span class="elsevierStyleInf">1&#47;2</span> of eight hours&#46; The only complication during hospital treatment was transitory thrombocytopenia&#44; which resulted from the technique&#46; The clinical profile was resolved in 24 hours&#46;</p><p class="elsevierStylePara">In conclusion&#44; in addition to the general support measures &#40;which should include gastric lavage with activated charcoal and forced diuresis&#44; both of which can eliminate an amount of free substance&#41; early use of haemoperfusion is effective for rapidly lowering circulating carbamazepine levels in those cases of acute poisoning for which extracorporeal techniques are indicated&#46;</p><p class="elsevierStylePara"><a href="grande&#47;1021718078&#95;f1&#95;pag129&#46;jpg" class="elsevierStyleCrossRefs"><img src="1021718078_f1_pag129.jpg"></img></a></p><p class="elsevierStylePara">Figure 1&#46; </p><p class="elsevierStylePara"><a href="grande&#47;1021718078&#95;t1&#95;pag129&#46;jpg" class="elsevierStyleCrossRefs"><img src="1021718078_t1_pag129.jpg" alt="Pharmacokinetics of carbamazepine before&#44; during and after haemoperfusion"></img></a></p><p class="elsevierStylePara">Table 1&#46; Pharmacokinetics of carbamazepine before&#44; during and after haemoperfusion</p>"
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        "resumen" => "<p class="elsevierStylePara">Carbamazepine is used in the treatment of epilepsy&#44; and also prescribed in neuralgic pain syndromes&#44; and certain affective disorders&#46; Carbamazepine intoxication with suicide attempt is a relatively common clinical problem that can result in coma&#44; respiratory depression&#44; arrhythmia&#44; hemodynamic instability and death&#46; The drug&#39;s relatively high molecular weight&#44; elevated volume of distribution and intense protein-binding render it difficult to extracorporeal removal&#44; but published experience with hemoperfusion or hemodialysis present variable results&#46; We describe a case report involving carbamazepine intoxication who was successfully treated with charcoal hemoperfusion&#46; With this treatment the half-life of carbamazepine was reduced with rapid lowering of carbamazepine levels and clinical improvement&#46; Based on our experience in this patient and a review of previously reported cases&#44; extended charcoal hemoperfusion should be considered for serious carbamazepine intoxication because free as well as bound drug fractions are eliminated via this technique&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">La intoxicaci&#243;n aguda por carbamazepina en los intentos autol&#237;ticos es un problema cl&#237;nico bastante com&#250;n que puede dar lugar a coma&#44; depresi&#243;n respiratoria&#44; arritmias&#44; inestabilidad hemodin&#225;mica y muerte&#46; El f&#225;rmaco tiene un peso molecular relativamente elevado&#44; un volumen de distribuci&#243;n moderadamente grande y una intensa fijaci&#243;n a las prote&#237;nas&#46; En caso de sobredosis&#44; estas caracter&#237;sticas farmacocin&#233;ticas hacen su eliminaci&#243;n extracorp&#243;rea dif&#237;cil&#44; por lo que la experiencia publicada con hemoperfusi&#243;n o hemodi&#225;lisis presenta resultados variables&#46; Se presenta un caso de intoxicaci&#243;n aguda por carbamazepina que fue tratado exitosamente con medidas de soporte general y una sesi&#243;n de hemoperfusi&#243;n con carb&#243;n activado&#46; Esta t&#233;cnica produjo una extracci&#243;n considerable del f&#225;rmaco&#44; mejorando r&#225;pidamente los signos cl&#237;nicos de intoxicaci&#243;n&#46; Basados en la experiencia con esta paciente y en la revisi&#243;n de otros casos publicados&#44; concluimos que en la intoxicaci&#243;n aguda por carbamazepina el tratamiento precoz con hemoperfusi&#243;n prolongada debe considerarse de elecci&#243;n&#46;</p>"
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