METABOLIC AND CARDIORESPIRATORY EFFECTS OF DOXAPRAM AND THEOPHYLLINE IN SLEEPING NEWBORN PIGLETS

To evaluate the contribution of a change in metabolic rate to ventilatory changes after the administration of respiratory stimulants, we studied the effect of two respiratory stimulants, doxapram and theophylline, on ventilation and metabolic rate during sleep in piglets. Metabolic rate (O2 consumption and CO2 production) was measured in a metabolic chamber, and alveolar ventilation (VA) was derived from arterial PCO2 and CO2 production. We studied the animals during a baseline period and for 2 h after the administration of theophylline or doxapram. With doxapram, there was no change in VA, metabolic rate, or arterial PCO2. In contrast, with theophylline, VA increased [20 +/- 14% (SD), P < 0.003] as a result of both an increased metabolic rate and hyperventilation. Doxapram, however, increased mean blood pressure (from 67 +/- 11 to 75 +/- 13 mmHg, P < 0.005), whereas theophylline did not result in blood pressure changes. In summary, during quiet sleep, doxapram, unlike theophylline, does not stimulate either respiration or metabolic rate. We speculate that the previous reports of increased ventilation after the administration of doxapram are due to the general stimulation of activity in the awake state, an effect not seen during sleep.