Categories: Respirology/ ICU

COPD and Hypoxic Drive: Mechanism

It is common dogma on the wards that oxygen therapy for chronic CO2 retainers should be targeted between 88-92% during a COPD exacerbation.

The mechanism often quoted is the “hypoxic drive to breath. The idea is that COPD patients tend to have chronically elevated levels of carbon dioxide due to the nature of their illness. As such, administering oxygen to these patients with COPD can be dangerous.

Their chronically elevated carbon dioxide levels result in loss of the hypercapneic-mediated respiratory drive and they rely solely on their “hypoxic” drive to breath. The patient’s chemo-receptors are already tolerant of high levels of carbon dioxide.

However, also contributory to the desaturation seen with higher oxygen levels is the Haldane effect. The Haldane effect states that deoxygenated hemoglobin has a higher affinity for CO2 because it is a better proton acceptor than oxygenated hemoglobin.

Therefore, increasing oxygen concentration in the blood by giving patients supplemental oxygen means carbon dioxide molecules will be displaced in favour of the oxygen, thereby reducing alveolar expulsion.

Finally, the most important mechanism is: hypoxic mediated vasoconstriction (aka V/Q mismatch).

When alveolar oxygen tension is reduced (i.e bronchoconstriction, mucus plugging), it induces vasoconstriction of pulmonary capillaries supporting the affected alveoli. This is meant to counteract possible shunting and normalize the V/Q ratio, a mechanism called hypoxic pulmonary vasoconstriction (see figure). The strongest determinant for hypoxic pulmonary vasoconstriction is the alveolar partial pressure of oxygen.

Therefore, providing a high fraction of inspired O2 (FiO2) will increase O2 tension in alveoli with a low level of ventilation (i.e scarred alveoli in setting of COPD), inhibiting hypoxic pulmonary vasoconstriction. As a result, alveoli with relatively impaired ventilation (which would be vasoconstriction normally) are no longer, leading to an increase in V/Q mismatch.

Therefore in summary (Abdo et al. 2012):

“In patients with COPD, hypoxic pulmonary vasoconstriction is the most efficient way to alter the V/Q ratios to improve gas exchange. This physiological mechanism is counteracted by oxygen therapy and accounts for the largest increase of oxygen-induced hypercapnia. A titrated oxygen therapy to achieve saturations of 88% to 92% is recommended in patients with an acute exacerbation of COPD to avoid hypoxemia and reduce the risk of oxygen-induced hypercapnia.”


  1. Abdo WF, Heunks LM. Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care. 2012;16(5):323. doi:10.1186/cc11475.
  2. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, Derenne JP. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis. 1980;16:747–754.
  3. organ, G.E., Mikhail, M.S., Murray, M.J. Clinical Anesthesiology: Fourth Edition. Chapter 22 Respiratory Physiology: The Effects of Anesthesia. Pg. 565.
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Dr. C Humphreys

Internal Medicine

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Dr. C Humphreys

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