Relative Effectiveness of Acetazolamide versus Medroxyprogesterone Acetate in Correction of Chronic Carbon Dioxide Retention1 ,2

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Abstract
We compared the relative efficacy of normalization of plasma bicarbonate with acetazolamide (ACET) versus medroxyprogesterone acetate (MPA) in correcting chronic CO2 retention during waking and sleeping states in patients with chronic obstructive airway disease (COPD). During placebo period, inspiratory effort (P0.1,) was high but insufficient to raise minute ventilation ( ) to the supernormal levels required for sufficient alveolar ventilation to normalize - Chronic ventilatory stimulation with either drug increased P0.1 (5 to 42%), mean inspiratory flow (14 to 31%), tidal volume (11 to 22%), and (16 to 19%) in 11 of 15 patients. This resulted in significant correction of their CO2 retention during waking and sleeping states ΔPaco2= -5 to -16 mmHg), despite the presence of high inspiratory impedance, shortened inspiratory time, and nonuniform ventilation-perfusion ratio. The acute ventilatory response to exogenous CO2 was not a good predictor of the chronic ventilatory response to MPA or even of the chronic response mediated by the ACET-induced increase in hydrogen ion concentration ([H+]). In 5 patients, ACET therapy was ineffective in correcting Paco2 despite increasing [H+] in plasma and cerebrospinal fluid (CSF). However, these same patients did correct with MPA coincident with an alkaline shift in plasma and CSF. The data confirm, using two means of chronic pharmacologic ventilatory stimulation, that insufficient inspiratory effort, as well as an abnormal breathing pattern, is a critical determinant of chronic CO2 retention. They further show that ACET induced acidification of plasma and cerebrospinal fluid does not cause sustained augmentation of ventilatory drive in a significant number of patients with COPD and chronic CO2 retention.