The hypoxic drive – an urban legend?

It is not unusual to see physicians painstakingly titrate oxygen flows with elaborate precision, especially in CO2 retaining patients with chronic obstructive pulmonary disease (COPD). I have occasionally come across novice ICU trainees cease oxygen therapy in dyspneic patients ostensibly to stimulate the hypoxic drive. The driving principle behind this line of thinking is the tradition-borne belief that supplemental oxygen may inhibit the hypoxic drive and lead to hypoventilation and rise in PCO2 levels. How important is the contribution of the hypoxic drive in patients with respiratory failure, especially among those with hypercapnia? Does supplemental oxygen really suppress ventilation in spontaneously breathing patients with COPD and lead to a rise in CO2 levels?

Aubier et al. studied 22 spontaneously breathing patients with acute exacerbation of COPD.They measured minute ventilation and performed arterial blood gases analysis, initially on room air, and subsequently while breathing pure oxygen through a Douglas bag. The minute ventilation dropped in the first few minutes but recovered rapidly to near baseline levels at approximately 10 minutes after oxygen administration. However, the CO2 levels continued to rise (Fig. 1). Clearly, hypoventilation was not the mechanism behind the rise in PCOin these patients.

Presentation3

Fig. 1 Minute ventilation (VE) decreased transiently after oxygen administration but recovered to baseline levels. The PCO2 levels continued to rise even after ventilation had recovered (From Abdo WF, Heunks LMA: Oxygen-induced hypercapnia in COPD: myths and facts. Critical Care 2012; 16:323)

Hypoxic pulmonary vasoconstriction and effect on PCO2levels

If oxygen therapy does not cause hypoventilation, what may be the mechanism behind the rise in CO2 levels? In chronic lung disease, blood flow through the lung is redistributed by hypoxia-induced vasoconstriction of the pulmonary vasculature. Blood vessels in regions of the lung that are poorly ventilated become constricted to match perfusion to ventilation and prevent shunting (flow of blood through the lungs without gas exchange). Supplemental oxygen results in an increase in the oxygen level within alveoli that are poorly ventilated with the abolition of hypoxia-induced vasoconstriction. This leads to a redistribution of blood flow from the relatively better ventilated to less ventilated regions of the lung. In effect, this results in an increase in perfusion relative to ventilation (low V/Q) in under-ventilated areas of the lung while the reverse occurs in the relatively well-ventilated areas of the lung (increase in alveolar dead space). Both these mechanisms may contribute to the rise in the alveolar and arterial COlevels.

The Haldane effect

About 10% of CO2 is carried in the blood as carbamino compounds, especially in combination with hemoglobin, as carbaminohemoglobin. Hemoglobin combines more avidly with CO2 when it is in the deoxygenated form. Thus, in the lung, as the hemoglobin takes up oxygen, it gives up the COby the Haldane effect. The CO2 is normally flushed out by ventilation. However, in a damaged lung, when the ventilation is inadequate, CO2 cannot be washed out adequately. The extra CO2 released from hemoglobin dissolves in the plasma with a rise in the PCO2 levels.

The bottom line

It is abundantly clear that the rise in CO2 levels seen in COPD patients with oxygen therapy is unrelated to the abolition of the “hypoxic drive” as was conventionally believed. The inhibition of ventilation is transient and insignificant; the PCO2 levels rise through other mechanisms. Theories and hypotheses apart, the bottom line is that supplemental oxygen should never be denied to hypoxic patients. The chances of death due to uncorrected hypoxia is overwhelmingly higher than possible harm from the administration of supplemental oxygen. Needless to add, most patients, regardless of their COlevels, do not need an oxygen saturation of more than 92%. Increasing the FiO2 aiming for much higher levels of oxygenation is not appropriate under most circumstances; less is more, so sayeth the wise intensivist!

References:

  1. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, et al. 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; 122:747-754.

 

 

 

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