Ventilatory Failure due to Metabolic Alkalosis

lthough it might be expected that an increase in A pH would have a depressing effect upon pulmonary ventilation, it'is generally held that respiratory depression is uncommon in patients with metabolic alkalosis. Thus, Tuller and Mehdil recently reported three cases of significant hypercapnia due to metabolic alkalosis, but stated that they could find only five other documented cases; and in a recent re vie^,^ it was stated that "the Pcoz of patients with metabolic alkalosis may be normal, low or slightly increased." It has been suggested that this apparent lack of respiratory compensation may be due to one or more factors: ( 1 ) that any tendency to hypercapnia will be opposed by a respiratory stimulant effect of the resulting hypoxia; (2) that, in clinical circumstances, metabolic alkalosis is often accompanied by a potassium deficit, intracellular as well as extracellular, and this will lead to migration of hydrogen ions into cells, including respiratory neurones, which will stimulate respiration; (3) that patients who do have respiratory depression in association with metabolic alkalosis are invariably azotemic or dehydrated and these factors account for their respiratory depression rather than the extracellular alkalosis. In view of these and similar statements about the rarity of respiratory depression in patients with metabolic alkalosis, and the possible reasons for this, we were surprised when we observed a number of patients with considerable hypercapnia which could not be explained by any other factor than an accompanying metabolic alkalosis. We therefore set out to investigate this problem with clinical and experimental observations. First, we reviewed our hospital records over a two-year period relating to arterial blood gas tensions and pH, looking for patients with a calculated plasma bicarbonate of 35 mEq/L or more. We found 105 such cases. Thirty of these were reiected from this study for one or more of the presence of acute disease (usually pneumonia, overt pulmonary edema, or postoperative atelectasis) which might have contributed to any ventilatory failure, (3) inadequate clinical data. Of the remaining 75 cases, 60 had some evidence of chronic alveolar hypoventilation as a primary cause of the increased plasma bicarbonate. The evidence in these cases included serial arterial blood gas measurements, and pulmonary function tests, supported by the history, physical findings, chest radiographs, and the clinical course of the illness. This method of selection yielded 15 patients with no evidence of any other condition leading to hypercarbia than a "primary" metabolic alkalosis. The relationship between arterial carbon dioxide tension and plasma bicarbonate in 31 observations from these 15 patients with severe metabolic alkalosis is shown in Figure 1. The different symbols in the figure refer to the factors thought to be responsible for the alkalosis (see legend). All of the patients had some hypercapnia and in eight cases the Pc02 was greater than 55 mm Hg. The association between plasma bicarbonate and arterial Pcoz was highly significant (r = 0.85). More than one observation was available in several patients. In some of these, the observations preceded the onset of alkalosis and in others they were obtained during correction of this. Many of these patients were also