The removal of the anoxic stimulus causes them to hypoventilate with further retention of carbon dioxide'.

The author, referring to such patients, stated the following theory: 'their respiratory activity depends mostly upon anoxic stimulation of the sino-aortic zones. In response to this article, Donald described an emphysema patient who developed a hypercapnic (16 kPa) coma during oxygen therapy and who had rapid clinical improvement after oxygen therapy was discontinued. Davies and Mackinnon hypothesized that oxygen intoxication could have led to accumulation of carbon dioxide (CO 2) in the body and cautioned against the use of oxygen in these patients. The authors found that, in all four studied subjects with emphysema and cyanosis, oxygen therapy led to increased cerebrospinal fluid pressures, which returned to baseline when oxygen was stopped.

After encountering two such cases, including one with a fatal coma, the authors set up a study to examine the effect of oxygen on intracranial pressure (that is, cerebrospinal fluid pressures measured through a lumbar puncture) in similar patients. In 1949, Davies and Mackinnon described oxygen-induced neurological symptoms in patients with cyanosis due to emphysema with chronic cor pulmonale.

Shunting vs dead space oxygen