Faculty Bibliography

The mechanisms of hypercapnia in eight patients with the 'Pickwickian' syndrome and obstructive sleep apnea (OSAS) were evaluated pretherapy and posttherapy (tracheostomy in seven patients and chronic nocturnal use of nasal CPAP in one). Four patients (correctors) became eucapnic within two weeks of therapy. Four others (noncorrectors) remained hypercapnic. Neither residual apneas, changes in pulmonary function, change in anatomic dead space, nor changes in ventilatory chemoresponsiveness differentiated the two groups, nor did the last three factors account for return to eucapnia in the correctors. The results indicated two separate mechanisms exist for chronic hypercapnia in OSAS: a critical balance between the ventilation during the time spent awake and hypoventilation due to apneas, a mechanism removed by treatment for obstructive apnea; and sustained hypoventilation independent of the apnea phenomenon and therefore not correctible. The subset of patients with the second mechanism appears to represent the true 'Pickwickian' syndrome and can be identified before therapy by measuring a low level of ventilation in the sustained awake state

Seven patients with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia were studied to define the pathophysiology of their respiratory failure. The patients had fever, cough, dyspnea, hypoxemia, and diffuse infiltrates on chest x-ray. Biopsies revealed a spectrum of alveolar filling, interstitial edema and infiltration, and fibrosis. The patients were studied on mechanical ventilation to assess the effect of positive end-expiratory pressure (PEEP) and supplemental oxygen on shunt fraction. Mean anatomic shunt (measured on 100% oxygen) was 34 +/- 8%, which increased significantly (p less than .001) to 43 +/- 9% when the FIO2 was decreased to 40% to 60% (physiologic shunt), indicating ventilation/perfusion (V/Q) imbalance or impaired diffusion. Increasing PEEP by 9 +/- 2 cm H2O reduced the anatomic shunt to 30 +/- 7% (p less than .01) and the physiologic shunt to 37 +/- 7% (p less than .02). There was a similar decrease in anatomic and physiologic shunts in five studies, a greater decrease in physiologic shunt in four, and a greater decrease in anatomic shunt in two. Evidence of alveolar recruitment with PEEP, measured by an increase in static thoracic compliance, was found in only one study. There was no correlation between the effect of PEEP on compliance and its effect on shunt. The data suggest that in patients with AIDS and P. carinii pneumonia, PEEP can decrease shunt by reducing the anatomic shunt, improving V/Q imbalance, and converting areas of anatomic shunt to areas of low V/Q. P. carinii pneumonia in patients with AIDS can produce a clinical and pathophysiologic pattern similar to that described in the adult respiratory distress syndrome

The relationship between the resting response to CO2 rebreathing and the ventilatory response to CO2 production during exercise was examined in 20 healthy untrained male subjects and in six patients with obesity hypoventilation syndrome. Patients were chosen because of a severely reduced response to CO2 rebreathing. There was no correlation between the CO2 rebreathing response and the exercise ventilatory response in the normal subjects, the patients, or in the group considered as a whole. This lack of correlation could not be accounted for by differences in ventilatory and occlusion pressure responses nor by reporting responses as a function of a change in hydrogen ion concentration. The independence of the CO2 rebreathing response and the exercise ventilatory response suggests the CO2 rebreathing response does not measure the relevant parameters of ventilatory control during exercise.

Sixteen patients with the obstructive sleep apnea syndrome (OSAS) were studied for 1-2 h while receiving continuous positive airway pressure (CPAP) delivered via a nasal mask. Obstructive apneas were obliterated in all. Eight patients had studies of genioglossal muscle activity (GG EMG) and one patient had computed tomograms (CT) of the upper airway while on nasal CPAP. The GG EMG studies showed two patterns: suppression and augmentation of GG EMG while on CPAP. The CT scan showed the airway to be narrowed while the patient was awake off CPAP. It returned to a normal caliber when CPAP was applied, despite sleep. These results are interpreted to suggest three potential mechanisms of action for nasal CPAP in OSAS: 1) reduced upper airway resistance due to prevention of sleep-induced collapse of the airway; 2) reduced upper airway resistance due to dilatation of the airway by nasal CPAP beyond its dimension in the awake state; and 3) possible stimulation of mechanoreceptors leading to an increase in airway tone while CPAP is applied