Effect of Theophylline on Metabolic and Ventilatory Response to Hypoxemia during Quiet Sleep in Piglets

Abstract

Theophylline, a drug frequently used in newborns, stimulates respiration and increases the metabolic rate in a sustained fashion; hypoxemia, on the other hand, decreases metabolic rate and increases ventilation slightly and, at times, only transiently. This study looked at the effect of theophylline on the metabolic and ventilatory response to hypoxemia in piglets. We studied two groups of piglets during normoxia and hypoxemia: first during a baseline period; and second, after the infusion of either theophylline or a placebo. All studies were done in quiet sleep, 2 d after instrumentation was performed to place vascular catheters and electroencephalographic electrodes. O2 consumption (VO2) and CO2 production (VCO2) were measured in a metabolic chamber, and alveolar ventilation (VA) was then derived from VCO2 and PaCO2. We found that theophylline did not abolish the small decrease in oxygen consumption brought about by hypoxemia. Nor did theophylline augment the ventilatory response to hypoxemia. In fact, the percent change in alveolar ventilation decreased slightly: going from 17 +/- 8% during the baseline period to 9 +/- 6% (p < 0.005) after theophylline administration. We found a significant increase in respiratory exchange ratio (R) in response to hypoxemia (from 0.87 +/- 0.05 to 0.97 +/- 0.04, p < 0.001). However, after the administration of theophylline, additional exposure to hypoxemia did not result in a change in R. In summary, our results show that, in sleeping newborn piglets, theophylline does not abolish the decrease in oxygen consumption observed in response to hypoxemia; nor does it enhance the ventilatory response to a moderate degree of hypoxemia.