Carbon dioxide is the chemical that most directly influences respiration via its effect on the efficiency of alveolar ventilation. The normal partial pressure of carbon dioxide in the blood is 4.0–6.0 kPa (30–45 mmHg). When this level rises, the pH of the CSF drops, which in turn causes excitation of the central chemoreceptors, and hyperventilation occurs (Patel and Majmundar [215], Tortora and Derrickson [272]).

Patients with COPD often retain carbon dioxide due to a change in the normal ventilation/perfusion ratio of the lungs and reduced alveolar ventilation. Chemoreceptors are no longer sensitive to a raised carbon dioxide level, so the falling PaO₂ becomes the principal respiratory stimulus. Giving high levels of supplementary oxygen can reduce the patient's stimulus to breathe, resulting in a fall in minute ventilation, which leads to respiratory depression, coma and death (Feller‐Kopman and Schwartzstein [78]). The link between giving high concentrations of oxygen and hypercapnia is complex and related to several processes in addition to reducing the patient's hypoxic drive.

Patients with known COPD should aim for target saturations of 88–92% and acute exacerbations treated with a 24–28% Venturi mask (GOLD [91]).

Nitrogen within the alveoli help to splint the air sacs open and prevent them from collapsing. Hyperoxia should therefore be avoided as high concentrations of oxygen wash out alveolar nitrogen, causing atelectasis (Hafner et al. [98]).

Prolonged hyperoxygenation and hyperoxia can result in pulmonary toxicity and lung injury. Hyperoxia increases the level of reactive oxygen‐derived free radicals, which causes an imbalance between oxidants and antioxidants, disrupting homeostasis at the cellular level (Hafner et al. [98]). A complex process ultimately results in lung fibrosis, which is permanent and irreversible (Mach et al. [139]). However, the degree of injury is related to the length of time and concentration of oxygen to which the individual is exposed. Where possible, long periods (i.e. 24 hours or more) of oxygen therapy above 50% FiO₂ should be avoided. However, treating hypoxia is the priority; use as little oxygen as possible to achieve the target oxygen saturations.

Oxygen is hazardous to patients with paraquat poisoning as it worsens pneumonitis and lung fibrosis. It should also be avoided in patients who have received bleomycin chemotherapy due to the risk of pulmonary toxicity; oxygen should only be given if the patient's saturations fall below 85% (O'Driscoll et al. [209]).