Correction of CO₂ retention during sleep in patients with chronic obstructive pulmonary diseases

Three normal subjects and 5 patients with chronic obstructive pulmonary disease and chronic CO₂ retention were studied to determine the effect of chronic ventilatory stimulation with medroxyprogesterone acetate (MPA) on ventilatory control and pulmonary gas exchange during sleep. All patients had lowered Pa(CO₂) after treatment with MPA /while awake. Using a randomized application of treatment and placebo conditions, 4 wk of MPA therapy in the normal subjects caused a reduction in Pa(CO₂) while awake (ΔPa(CO₂) -4 to -7 mmHg) and during non-REM sleep (ΔPa(CO₂) -5 to -7 mmHg). The response consisted of an increased minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI) awake and during non-REM sleep. In the patient group, 4 wk of MPA therapy caused significant reductions in Pa(CO₂) while awake (from 54 ± 2 to 47 ± 2 mmHg) and during non-REM sleep (from 57 ± 2 to 49 ± 2 mmHg). Minute ventilation, tidal volume, and mean inspiratory flow increased to a similar extent while awake and during all sleep stages. Improvement in Sa(O₂) during sleep induced by treatment was attributable to an increase in alveolar ventilation rather than a decrease in alveolar-arterial oxygen partial pressure difference. Medroxyprogesterone acetate elicited chronic increases in inspiratory effort, tidal volume, and alveolar ventilation while awake and during all sleep stages in selected patients with chronic CO₂ retention despite severe mechanical impairment and maldistribution of ventilation:perfusion. The drug drives ventilation by a mechanism of action that is independent of many other peripheral and 'central' ventilatory stimuli and/or inhibitors, including higher central nervous system influences on ventilatory control that are dependent on the state of wakefulness.