Effects of acetazolamide on ventilatory, cerebrovascular, and pulmonary vascular responses to hypoxia.
BACKGROUND
Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000-3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction.


OBJECTIVE
We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR).


METHODS
In this double-blind, placebo-controlled, randomized study, nine subjects ingested 250 mg acetazolamide every 8 h for 3 d. On the fourth test day, we measured the responses of ventilation, PVR, and CBF to acute isocapnic hypoxia (20 min) and sustained poikilocapnic hypoxia (4 h). Ventilation was measured with pneumotachography. Hypoxia was achieved with dynamic end-tidal forcing. The maximum pressure difference across the tricuspid valve (DeltaPmax, a good index of PVR) was measured with Doppler echocardiography. CBF was measured by transcranial Doppler ultrasound.


RESULTS
In normoxia, acetazolamide increased ventilation and reduced DeltaPmax, but did not influence CBF. The ventilatory and CBF responses to acute isocapnic hypoxia were unaltered, but the rise in DeltaPmax was reduced by 57%. The increase in DeltaPmax by sustained poikilocapnic hypoxia observed after placebo was reduced by 34% after acetazolamide, the ventilatory response was increased, but the CBF response remained unaltered.


CONCLUSIONS
Acetazolamide has complex effects on ventilation, PVR, and CBF that converge to optimize brain oxygenation and may be a valuable means to prevent/treat high-altitude pulmonary edema.
Teppema
Luc J
LJ
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Balanos
George M
GM
Steinback
Craig D
CD
Brown
Allison D
AD
Foster
Glen E
GE
Duff
Henry J
HJ
Leigh
Richard
R
Poulin
Marc J
MJ
D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D000532:Altitude Sickness / Q000150:complications / Q000517:prevention & control*; D001808:Blood Vessels / Q000000981:diagnostic imaging; D001921:Brain / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000517:prevention & control; D008168:Lung / Q000098:blood supply; D008297:Male; D010919:Placebos; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000209:etiology / Q000517:prevention & control*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D018608:Ultrasonography, Doppler
D010919:Placebos; D000086:Acetazolamide