Low-dose doxapram for apnea unresponsive to aminophylline in very low birthweight infants

This study was designed to test whether the addition of low-dose (less than or equal to 1.5 mg/kg/h) doxapram may help wean from positive airway pressure very low birthweight (less than or equal to 1250 g) infants with apnea unresponsive to aminophylline. Doxapram infusion was started at 0.1 to 0.5 mg/kg/h and increased as necessary up to a maximum of 1.5 mg/kg/h. Average birthweight (N = 12) was 1026 +/- 170 g (mean +/- SD, range 740 to 1250), gestational age 27.8 +/- 2.6 weeks (range 24 to 34), postnatal age 24.2 +/- 9.4 days (range 13 to 40), central spun hematocrit 44% +/- 4% (range 38% to 48%), and theophylline level 57.1 +/- 7.7 mumol/L. Doxapram therapy resulted in weaning to a head box in 11 of 12 patients; two required a subsequent course after stopping doxapram. Since the only observed toxicity was mild irritability in one patient, we conclude that very low birthweight infants with apnea unresponsive to aminophylline and older than 1 week of age often respond to the addition of low-dose doxapram with only minimal side effects. Since there was a negative correlation between theophylline level and the effective doxapram dose (r = -.64, N = 13, P less than .05), we recommend that treatment with doxapram be considered in the United States only in those infants with a theophylline level greater than or equal to 88.8 mumol/L, in order to limit the cumulative dose of benzyl alcohol administered.