The Effect of Dichlorphenamide on Blood and Cerebrospinal Fluid Acid-Base State in Chronic Ventilatory Failure

Abstract

1. Pco₂, [HCO⁻₃] and [H⁺] have been measured in arterial blood and CSF in twenty-three patients with chronic airways obstruction and five patients without chest disease. 2. Through a range of Pco₂ in the CSF from normal to 79 mmHg there was a direct linear relation between Pco₂ and [H⁺]. The slope of this relation (0·41 nmol l⁻¹ mmHg⁻¹) was similar to that reported in experimental studies in animals and would appear to represent the extent to which regulatory mechanisms can protect CSF [H⁺] against the acidosis of chronic hypercapnia. 3. There was also a direct linear relation between CSF [HCO⁻₃] and arterial plasma [HCO⁻₃], the rise in [HCO⁻₃] in the CSF being less than that in the blood. 4. Thirteen patients were re-studied after receiving the carbonic anhydrase inhibitor dichlorphenamide for 1 week. A metabolic acidosis developed in the arterial blood. In the CSF Pco₂ and [HCO⁻₃] fell but [H⁺] did not change. CSF [H⁺] is maintained constant and normal in other forms of chronic metabolic acidosis but it seems likely that the constancy observed in the present study was fortuitous. Possible reasons for this are discussed, and it is concluded that variability in responsiveness to ventilatory stimuli between patients is the most likely explanation.