title: Hyperventilation and cerebrospinal fluid acidosis caused by topiramate.
abstract: OBJECTIVE
  To report a case of hyperventilation caused by topiramate therapy and propose a pathophysiologic mechanism for this disorder.
  
  
  METHODS
  A 52-year-old woman with refractory seizure disorder was admitted to the burn care unit with burns over 10% of her body. Her seizure medications, unchanged and well tolerated for several months, included carbamazepine 1200 mg, lamotrigine 500 mg, phenobarbital 80 mg, and topiramate 150 mg per day. During hospitalization, despite a relatively normal arterial pH, the woman developed persistent hyperventilation, with respiratory rates up to 50 breaths/min. Alkalinization did not reduce the hyperventilation. Thoracic contrast-enhanced computed tomographic scan ruled out pulmonary embolism and persistent pneumonia. Salicylate and biguanide screening were negative; results of repeated thyroid and liver function tests were normal. Cerebral magnetic resonance imaging excluded a cerebral pathology. After cerebrospinal fluid (CSF) analysis showed acidosis (pH 7.14), topiramate was withdrawn and the patient's general condition rapidly improved. Forty-eight hours later, the CSF pH had increased to 7.26. The woman was discharged from the burn care unit on the 42nd hospital day.
  
  
  CONCLUSIONS
  Hyperchloremic normal anion gap metabolic acidosis, which can lead to hyperventilation, has been reported as an adverse effect of topiramate treatment. However, our patient had respiratory alkalosis. Concurrent etiologies of peripheral hyperventilation were excluded, leaving central neurogenic hyperventilation as the remaining etiology. Such central neurogenic hyperventilation associated with topiramate has previously been reported in intensive care. Our case report demonstrates CSF acidosis. Withdrawing topiramate reduced both CSF acidosis and hyperventilation. The mechanism of topiramate-induced CSF acidosis remains unclear. According to the Naranjo probability scale, the relationship of hyperventilation to administration of topiramate in our patient was probable.
  
  
  CONCLUSIONS
  Normal doses of topiramate may provoke central neurogenic hyperventilation, as a result of CSF acidosis. The acid-base status of critically ill patients receiving topiramate should be monitored carefully.
authors.affiliation: Department of Anesthesia and Intensive Care Unit, Military Teaching Hospital Sainte Anne, Toulon-Armees, France. ambroise.montcriol@free.fr
authors.forename: Ambroise
authors.initials: A
authors.lastname: Montcriol
authors.forename: Eric
authors.initials: E
authors.lastname: Meaudre
authors.forename: Nadia
authors.initials: N
authors.lastname: Kenane
authors.forename: Yves
authors.initials: Y
authors.lastname: Asencio
authors.forename: Julien
authors.initials: J
authors.lastname: Bordes
authors.forename: Bruno
authors.initials: B
authors.lastname: Palmier
mesh_terms: D000138:Acidosis / Q000134:cerebrospinal fluid* / Q000139:chemically induced*; D000927:Anticonvulsants / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D006985:Hyperventilation / Q000139:chemically induced*; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose