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CO₂ inhalation has been previously reported as a treatment for central sleep apnea both when associated with heart failure or where the cause is unknown. Here, we evaluated a novel CO₂ supply system using a novel open mask capable of comfortably delivering a constantly inspired fraction of CO₂ (FICO2) during sleep. We recruited 18 patients with central sleep apnea (13 patients with cardiac disease, and 5 patients idiopathic) diagnosed by diaphragm electromyogram (EMG) recordings made during overnight full polysomnography (PSG) (night 1). In each case, the optimal FICO2 was determined by an overnight manual titration with PSG (night 2). Titration commenced at 1% CO₂ and increased by 0.2% increments until central sleep apnea (CSA) disappeared. Patients were then treated on the third night (night 3) with the lowest therapeutically effective concentration of CO₂ derived from night 2. Comparing …