Respiratory and nonrespiratory effects of doxapram in congenital central hypoventilation syndrome

Abstract

Doxapram is a respiratory stimulating drug that affects both peripheral chemoreceptors and medullary respiratory and nonrespiratory neurons. We administered doxapram 60 2 infants with congenital central hypoventilation syndrome. In 6 separate trials at a dose range of 0.32 to 2.0 mg per kg of body weight per min, quiet-sleep tidal volume increased from 4.9 +/- 1.0 to 8.5 +/- 0.9 ml per kg of body weight, minute ventilation increased from 140 +/- 38 to 286 +/- 31 ml per kg of body weight per min, and alveolar PCO2 decreased from 60 +/- 5 to 32 +/- 2 mm Hg. In all instances, the maximal quiet-sleep ventilatory response was achieved within 10 min. The ventilatory response to steady-state CO2 breathing was not improved with doxapram. A continuous infusion of doxapram for 5.2 days in one infant successfully maintained normal quiet-sleep ventilation. In both infants, multiple nonrespiratory effects of doxapram occurred; enteral administration was associated only with generalized neuromuscular stimulation, but the 5-day intravenous infusion was also associated with acute hepatotoxicity and a perforated duodenal ulcer. The medullary respiratory neurons in central hypoventilation syndrome may be incapable of responding to doxapram, and the ventilatory responses observed may be due entirely to stimulation of peripheral chemoreceptors. Although quiet-sleep ventilation can be successfully maintained with intravenous and enteral administration of doxapram, and tachyphylaxis has not been observed, we have been unable to avoid at least the neuromuscular manifestations of nonrespiratory medullary stimulation.