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Inicio Revista de Psiquiatría y Salud Mental (English Edition) Metabolic acidosis and topiramate. Use of Winters’ formula
Journal Information
Vol. 7. Issue 2.
Pages 96 (April - June 2014)
Vol. 7. Issue 2.
Pages 96 (April - June 2014)
Scientific letter
DOI: 10.1016/j.rpsmen.2014.02.002
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Metabolic acidosis and topiramate. Use of Winters’ formula
Acidosis metabólica y topiramato. Utilidad de la fórmula de Winters
Paula Rubio, August Supervía??
Corresponding author

Corresponding author.
, Alfons Aguirre, José Luís Echarte
Servicio de Urgencias, Hospital del Mar, Barcelona, Spain
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Topiramate is a drug introduced in Europe in 1995 for the treatment of hard-to-control epilepsy. The drug is also effective in the treatment of bipolar disorder, migraines, neuropathic pain, alcohol dependence, essential tremor, obesity and eating disorders. One of its side effects is hyperchloremic metabolic acidosis without anion gap,1,2 which can appear in up to 40% of the patients who receive topiramate at therapeutic doses; it is more frequent and severe in the case of acute poisoning.1 However, in the cases of acute intoxication, it is usually associated with other drugs, which can also influence acid–base balance. We report the case of a patient who presented with metabolic acidosis after an overdose of 2 drugs, one of them being topiramate.

This was a 38-year-old woman with a history of gastric reduction due to obesity and cluster B personality disorder. She was on treatment with venlafaxine, mirtazapine, topiramate and lorazepam. She came to emergency treatment for autolytic-intention medicine overdose with topiramate and lorazepam of uncertain dosage and time. Upon arrival the patient was found to be Glasgow 14, tending to somnolence, with the rest of the examination being normal. She was given activated charcoal. The analytical analyses showed hyperchloremic metabolic acidosis with normal anion gap: pH 7.29, pCO2 41mmHg, bicarbonate 19.7mmol/l, excess of bases ▭6.9, chlorine 113.4mmol/l, and anion gap 14.6. After 18h her level of consciousness improved, being in Glasgow 15, and the pH was normal, although low levels of bicarbonate (18.2mmol/l) and hyperchloremia (117mmol/l) persisted. Nevertheless, given her clinical stability, the patient was discharged after psychiatric assessment.

Topiramate, besides potentially causing metabolic acidosis, can also produce central neurogenic hyperventilation. This is probably due to its inhibitory effect on the carbonic anhydrase in the brain and to the subsequent LCR acidosis.2 In such a situation, the clinical picture develops with hyperventilation, arterial hypotension and different degrees of altered consciousness and cognitive functions.1 In these cases, gastric lavage and administering activated charcoal are of little use because topiramate is very rapidly absorbed.1 The perfusion of sodium bicarbonate as treatment for acute intoxication with acidosis is controversial.1,2 However, some authors recommend administering alkaline solutions in cases of acidosis secondary to chronic treatment.3

In the case that we present here, topiramate might be responsible for the metabolic acidosis with normal anion gap that the patient had. However, when we apply Winter's formula (expected pCO2=1.54×HCO3+8.36±1.11), we see that the expected pCO2 is 38.7±1.11mmHg, a value less than that presented by our patient. This formula is extremely useful for calculating the value of pCO2 starting from a specific value of serum bicarbonate. Consequently, when the pCO2 values are different from that expected when applying Winter's formula, it can be concluded that there is another process that is influencing the genesis of acidosis. In this case, the discrepancy between the expected and real pCO2 values led us to suspect the presence of a component of respiratory depression attributable to the benzodiazepines. It can be interpreted that the presence of other toxic substances (such as the benzodiazepines in this case) can eliminate the compensatory respiratory effect secondary to acidosis produced by topiramate. The conclusion is that the finding of abnormally elevated pCO2 with respect to the degree of existing acidosis can alert one to the possible presence of a component of respiratory depression that can be produced by other toxic substances.

D. García-Gil, V. Pérez Vázquez, C. Asencio Méndez, J. García-Torrejón.
Intoxicación aguda por topiramato con intención suicida.
Med Clin (Barc), 133 (2009), pp. 766-767
S. Franco Hidalgo, J.M. Prieto de Paula.
Intoxicación aguda por topiramato: causa de acidosis metabólica y de hiperventilación central.
Med Clin (Barc), 136 (2011), pp. 224-225
L. Fernández de Orueta, J. Esteban Fernández, H. Aichner, A. Casillas Villamor, S. Rodríguez Álvarez.
Acidosis metabólica inducida por topiramato: a propósito de un caso.

Please cite this article as: Rubio P, Supervía A, Aguirre A, Echarte JL. Acidosis metabólica y topiramato. Utilidad de la fórmula de Winters. Rev Psiquiatr Salud Ment (Barc.). 2013;7:96.

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