CLINICAL IMPLICATIONS

The most important cause of respiratory failure is derangement of lung mechanics. However, respiratory failure does not develop in all patients, even those with severe impairment of pulmonary function. It has long been suspected that those patients who have the poorest chemosensitivity are the ones in whom CO2 retention is most likely to develop when the performance of the chest bellows is reduced. The evidence for this is indirect. For example, normal offspring of hypercapnic subjects with COPD demonstrate significantly lower ventilatory and occlusion pressure responses to hypoxia and hypercapnia (~60% lower) than do normal offspring of eucapnic subjects with COPD.
The CO2 sensitivity of children who have retained CO2 because of upper airway obstruction resulting from hypertrophy of the adenoids and tonsils is depressed, even after the tonsils and adenoids have been removed. Asthmatic patients who have retained CO2 during an asthmatic attack also show persistently low ventilatory responses to CO2, even after recovery from the asthmatic episode. Moreover, subjects who have had asphyxial, near-fatal episodes of asthma display lower ventilatory and occlusion pressure responses to hypoxia than do either age-matched normal subjects or asthmatic subjects with no history of near-fatal episodes.
There is also a small group of subjects who retain CO2 even though lung function is normal. In some of these patients, the cause of the depressed CO2 sensitivity is not known, but in others it seems to be associated with specific diseases, certain metabolic abnormalities, such as alkalosis, or the long-term administration of respiratory depressant drugs, such as methadone. These conditions are summarized in Table 1. In a few conditions listed in Table 2, only the ventilatory response to hypoxia is depressed. Individuals with these conditions are able to maintain blood gas tensions within usual limits because of their normal CO2 drive. However, when CO2 sensitivity is reduced by the administration of drugs (e.g., premedication before surgery), significant hypoxemia can develop. Depressed ventilatory responses to hypoxia may also increase the tendency for CO2 retention to develop in COPD and may be a risk factor for acute mountain sickness.

TABLE 1. Conditions sometimes associated with depressed responses to hypercapnia and hypoxia

TABLE 2. Conditions associated mainly witha decreased response to hypoxia

Certain conditions seem to predispose to heightened responses to CO2 or hypoxia, even when the lungs are normal. These conditions are listed in Table 3.

TABLE 3. Conditions associated with increased responses to carbon dioxide and/or hypoxia

Abnormalities in mechanoreceptor function also can influence gas exchange. Patients with chronic airway obstruction who breathe with small tidal volumes tend to retain CO2, whereas those who breathe with larger tidal volumes do not. The small tidal volumes are caused by abbreviated inspiratory time and perhaps by heightened pulmonary or chest-wall receptor activity. Heightened mechanoreceptor activity may also be responsible for dyspnea in some patients with interstitial lung disease, as vagal blockade at times alleviates this sensation.