Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts

Abstract

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The eVects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/ day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances. (Arch Dis Child 2001;84:68-71) Keywords: acetazolamide; cerebrospinal fluid; hydrocephalus; ventriculopleural shunts Congenital and acquired obstructive hydrocephalus are common problems in children, with an incidence of 0.4-0.8 per 1000 liveborns and stillbirths. 1 The majority of these patients are managed with ventriculoperitoneal shunts. The ability of the peritoneal membranes to absorb cerebrospinal fluid (CSF) may be decreased after intra-abdominal infections or surgery, such that a ventriculoperitoneal shunt may not provide adequate decompression of the ventricles. In this situation, CSF may need to be drained from the ventricle into other body cavities, such as the pleural space. The success of ventriculopleural shunts may be limited by the rate of absorption of CSF by the pleural membranes. Respiratory insuYciency may develop with the accumulation of large volumes of CSF in the pleural space. Therefore, attempts to limit CSF production may be beneficial in this situation.Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease CSF production in animal models and is used in both adults and children to treat conditions such as pseudotumor cerebri.2 3 There are, however, no studies reporting the change in CSF volume produced by children after extended treatment with ACTZ. We report our use of ACTZ in two children who had experienced multiple ventriculoperitoneal shunt failures and who were temporarily managed with externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. We evaluated the eVect of ACTZ on CSF production and the subsequent tolerance of the ventriculopleural shunt. Case reportsPatient 1 was a 1 year old male born at 24 weeks gestation with multiple medical problems, including bronchopulmonary dysplasia (BPD) and respiratory failure requiring mechanical ventilatory support via a tracheostomy. He also had a right femoral Broviac type indwelling central catheter for parenteral nutrition and medications. He developed hydrocephalus secondary to an intraventric...

The value of transcranial Doppler imaging in children with tuberculous meningitis

“…Carbonic anhydrase inhibitors (acetazolamide) and loop diuretics (furosemide) exert their effect on ICP by reducing CSF production at the choroid plexus [19]. Acetazolamide has a rapid onset of action and has been found to reduce CSF production in humans by 6-50 % [20].…”

Cerebrospinal fluid rhinorrhea: endoscopic repair based on a combined diagnostic approach

“…The layering of graft material with fi brin glue can reduce the rate of postoperative recurrence of CSF rhinorrhea. Intracranial pressure reducing measures like lumbar drainage of CSF and the use of drugs like [17] acetazolamide have been useful in faster and effective healing of CSF fi stulae. Causes of recurrence of CSF leak include failure to localize the exact site of leak, diffi culty in controlling the underlying cause of leak like a chronic obstructive pulmonary disease or hypertension, failure on the part of the patient to follow the postoperative advice completely etc.…”

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus

“…17,74,88,93 As reviewed earlier, the charge gradient created by transport of positive ions (primarily Na + ) into the ventricular space is balanced by the cotransport of bicarbonate, which is produced by CA in the intracellular compartment. However, the precise mechanism by which acetazolamide reduces CSF production is not completely understood.…”

“…Nonetheless, pharmacological (e.g., acetazolamide) and surgical (e.g., choroid plexus cauterization [CPC]) strategies that decrease CSF production have been shown to be successful for specific hydrocephalus subtypes. 17,109 Here, we review the physiological and molecular mechanisms of CSF secretion by the choroid plexus and provide evidence for the role of increased CSF production in animal models and children with hydrocephalus. We propose that CSF hypersecretion is probably an underrecognized mechanism of hydrocephalus in at least certain pediatric hydrocephalus subtypes.…”

“…69,123 Partial reduction of CSF secretion by pharmacological inhibition of CA by acetazolamide highlights the importance of this enzyme in CSF homeostasis. 17,130 NKCC1 is highly expressed in the luminal (apical) membrane of the CPE. 13 In most secretory epithelia, NKCC1, the Na + /K + -ATPase, and K + channels are located on the basolateral membrane, and Cl -channels are located on the apical membrane.…”