Effects of acetazolamide and furosemide on ventilation and cerebral blood volume in normocapnic and hypercapnic patients with COPD.
OBJECTIVE
Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume (CBV), to short-term changes in arterial PCO(2) was measured.


METHODS
Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa) and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy.


RESULTS
Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory (Delta VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2), respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state.


CONCLUSIONS
Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state.
van de Ven
Marjo J T
MJ
Department of Pulmonology Dekkerswald, University Medical Center Nijmegen, Groesbeek, Nijmegen, The Netherlands. m_vandeven60@hotmail.com
Colier
Willy N J M
WN
van der Sluijs
Marco C
MC
Oeseburg
Berend
B
Vis
Piet
P
Folgering
Hans
H
D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000471:Alkalosis / Q000378:metabolism; D001810:Blood Volume / Q000187:drug effects*; D002245:Carbon Dioxide / Q000032:analysis*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002908:Chronic Disease; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012119:Respiration / Q000187:drug effects*
D004232:Diuretics; D002245:Carbon Dioxide; D005665:Furosemide; D000086:Acetazolamide