What evidence proves the hypoxic drive theory wrong?

Ironically, and surprisingly, there has never been a real scientific study done to prove the hypoxic drive theory.  On the contrary, many studies have shown the theory to be nothing more than a myth.

For instance, in 1989 Greggory A. Schmidt M.D. and Jesse B. Hall M.D. wrote an article, "Oxygen Therapy and Hypoxic Drive to Breath:  Is There Danger in the patient with COPD?" that was published in Critical Care Digest questioning the popular hypoxic drive theory.  (1)

Schmidt and Hall reported that little science was used in coming up with this theory.  No COPD patients were given oxygen and had their ventilations simultaneously measured.  (1)

In fact, they report that in one study COPD patients were given oxygen and they found that "the rise in CO2 could not be accounted for by hypoventilation."

Likewise, a follow up study determined that supplemental oxygen to COPD patients caused decreased ventilation in some, unchanged ventilation in some, and normal ventilation in some. They wrote that "The commonest pattern was of early hypoventilation followed by a return to baseline.

Schmidt and Hall "attributed the rise in CO2 to an increase in the dead space to tidal volume ratio (also referred to as ventilation/ perfusion mismatching) consequent to oxygen therapy, though the mechanism for this change is unclear."

Abier et al in 1980 showed that 20 COPD patients in acute respiratory failure receiving 5lpm oxygen for 30 minutes showed a 14% reduction in minute ventilation with only a small rise in PaCO2, despite a large rise in PaO2.  They concluded that there was no correlation with the rise in PaCO2 and the fall in ventilation. (2)

Abier et al in 1980 also studied the effects of 100% oxygen on minute ventilation in COPD patients presenting with acute respiratory failure.  The concluded, once again, that despite the slight rise in CO2 and drop in minute ventilation, there was no correlation with the rise in PaCO2 and the fall in ventilation. (3)

In a 2000 study by Robinson et al, 22 COPD patients were given 100% oxygen and ventilations fell by an average of 20% for those who were CO2 retainers, yet the cause was determined to be due to ventilation/ perfusion mismatching, "not just a failure of ventilatory response to the increase in PaCO2."  (4)

A 2007 by Dick et al showed that oxygen induced hypercarbia was not caused by knocking out the drive to breathe.  In stable patients with COPD given 100% oxygen over a period of 15 minutes, oxygen saturations increased by about 7.6% and PaCO2 rose by about 6.6 mmgH, while minute ventilation was unchanged in all those studied. (5)

A 2014 study by Savi et all concluded the following:

Our results support the hypothesis that increasing the FiO2 in CO2-retaining COPD subjects on NIV does not cause any clinically important change in CO2 retention.  (6)

The also note:

The PaCO2 commonly rises somewhat when a patient with COPD receives supplemental oxygen, but carbon dioxide narcosis due to oxygen therapy is uncommon, and patients should not be kept hypoxemic for fear that oxygen therpay could aggravate carbon dioxide retention. The increase in CO2 is probably due to a change in dead space or shift of the hemoglobin-oxygen binding curve, rather than decreased respiratory drive.  The expected rise should not be specifically treated unless it is excessive, resulting in a trend toward acute respiratory acidosis on serial arterial blood gas analysis, with cenetral nervous system or cardiovascular side effects.  Carbon dioxide narcosis may occur with excessive FiO2, but is much less likely with low flow, controlled oxygen therapy.(6)

Despite all these studies, the hypoxic drive theory continues to be the gold standard theory regarding treatment of patients with COPD.  However, enough evidence now exists to support that supplemental oxygen is not as detrimental to COPD-CO2 retainers as once suspected.

References:

1. Schmidt, Greggory A., Jesse B. Hall M.D "Oxygen Therapy and Hypoxic Drive to Breath:  Is There Danger in the patient with COPD?" Critical Care Digest, 1989, 8, pages 52-53
2. Aubier M., Murciano D, Fournier M, Milic-Emili J, Pariente R, Derenne JP, "Central respiratory drive in acute respiratory failure of patients with chronic obstructive pulmonary disease, American Review of Respiratory Disease, 1980 volume 122, number 2, pages 191-199
3. Aubier M, Murciano D, Milic-Emil 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," American Review of Respiratory Disorders, 1980, volume 122, number 5, pages 747-754
4. Robinson, Tracey D., et al, "The Role of Hypoventilation and Ventilation-Perfusion Redistribution in Oxygen-induced Hypercapnia during Acute Exacerbations of Chronic Obstructive Pulmonary Disease," American Journal of Respiratory adn Critical Care Medicine, 2000, volume 161, pages 1524-1529
5. Dick, C.R., et al, "O2-induced change in ventilation and ventilatory drive in COPD," American Journal of Respiratory and Critical Care Medicine," volume 155, no. 2, Feb., 1997, pages 609-614
6. Savi, Augusto, et al, "Influence of FiO2 During Noninvasive Ventilation in Patients with COPD," Respiratory Care, March, 2014, Volume 59, Number 3, pages 383-387

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