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 PaCO2 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 PaCO2 while awake (delta PaCO2 -4 to -7 mmHg) and during non-REM sleep (delta PaCO2 -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 PaCO2 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 SaO2 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 effect, 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 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 influenced on ventilatory control that are dependent on the state of wakefulness.