Rationales to use / Dosing Recommended
After 4 days, if the pressure remained elevated, acetazolamide could be
added at a dose of 250 mg/6 h orally. Corticosteroids were allowed at
doses of up to 50 mg/day of hydrocortisone to alleviate reactions to the
amphotericin B infusions.
Treatment of
elevated CSF pressure in granulomatous meningitis is aimed at decompressing the
fluid, either by ventricular drainage or by medical means, such as treatment
with acetazolamide or mannitol. These agents reduce secretion of the CSF or
render the plasma relatively hypertonic, thus causing an osmotic gradient from
the CSF to the plasma.
(Renal Adjustment)
For patients who weighed >45 kg, the starting dosage was 1 tablet
given every 6 h. The dose interval was reduced according to serum creatinine
level, as follows: the interval was reduced to 12 h for patients with a serum
creatinine level of 186–266 μM and to 24 h for those with a serum
creatinine level of 267–354 μM; no tablets were given to patients whose
level increased to >354 μM.
(Weight)
For patients who weighed 35–45
kg, the starting dosage was 1 tablet given every 8 h; the dose interval was
reduced to 24 h for patients with a serum creatinine level of 186–266 μM,
and no tablets were given to patients whose level increased to >266 μM.
Oral potassium supplements were given if the patient's serum potassium level
decreased to <3.0 mM, and bicarbonate supplements were provided if
the venous bicarbonate level decreased to <15 mM.
For the patient with
cryptococcal meningitis, a 2-month course of acetazolamide therapy at a total
dose of 500 mg/day was associated with resolution of the papilledema and
restoration of visual acuity. The
patient with C. immitis meningitis required 4 years of acetazolamide
therapy; intermittent discontinuation of acetazolamide resulted in recurrence
of headaches and visual disturbances. No significant electrolyte abnormalities
or adverse events were observed. The papilledema did not recur after the
cessation of therapy.
Chronically elevated ICP may lead to serious sequelae, including visual
and hearing loss, systemic hypertension, severe cephalgia, and depressed mentation.
* Acetazolamide may be used to reverse chronically elevated ICP due to
fungal meningitides and deserves further investigation.
Franks Shann
- 5-10 mg/kg (Adult 100-250mg) q6-8H
Rationales NOT to use
Discussion. This
evaluation of acetazolamide for the treatment of elevated intracranial pressure
complicating cryptococcal meningitis was terminated prematurely, because
independent review strongly suggested that acetazolamide
therapy was harmful, with an excess of severe acidosis and adverse events.
This study has insufficient power to characterize the effect, if any, of
acetazolamide on intracranial pressure, headache, or Karnofsky score. The
severity of the acidosis, combined with hypokalemia, suggests that
acetazolamide has an additive or synergistic toxicity with amphotericin B
resulting from renal tubular dysfunction.
The antisecretory effects of acetazolamide may be insufficient to
reduce intracranial pressure in the face of severe outflow obstruction (caused
by cryptococci or capsular polysaccharide) of CSF drainage through the
arachnoid villi [2]. Acetazolamide should not be used in combination with
amphotericin B for the treatment of cryptococcal meningitis. This study does
not address whether acetazolamide may be beneficial for patients receiving
lipid formulations of amphotericin B; for HIV-negative patients; for the
palliation of symptoms of elevated intracranial pressure, if used in areas
where amphotericin B is not affordable [10]; or after the amphotericin B course
has finished.
Mannitol has no proven value in
reducing pressure in cryptococcal meningitis. Acetazolamide or corticosteroids to control CSF pressure unassociated with immune reconstitution
inflammatory syndrome (IRIS) should also
be avoided.
A Randomized, Double‐Blind, Placebo‐Controlled Trial of
Acetazolamide for the Treatment of Elevated Intracranial Pressure in Cryptococcal
Meningitis
[ Newton et al. - 35(6):769-72 · September
2002 ]
We conducted a trial of oral
acetazolamide for the treatment of cryptococcal meningitis in 22 Thai adults
with headache and an opening cerebrospinal fluid pressure of >/=200 mm H(2)0.
The trial was terminated prematurely
because patients who received acetazolamide developed significantly lower
venous bicarbonate levels and higher chloride levels and had more-frequent
serious adverse events than did subjects who received placebo.
Acetazolamide should not be
used as therapy for increased ICP management since it may cause hyperchloremic acidosis and does not result in a decrease
in ICP (AI)
- All accessed on 24/10/2018 -
