Caffeine and
doxapram are two
respiratory stimulants used in the treatment of
apnea in newborns. When used concurrently, these drugs may produce interactive effects on the control of breathing in the newborn. The ventilatory effects of these drugs, given alone or together, were measured during 150 min of
drug infusion in two groups of awake lambs 2-5 days old. The first group (n = 5) received a
caffeine loading dose of 10 mg/kg followed by a maintenance dose of 0.1 mg/kg/h and incremental doses of
doxapram: 0.25, 0.5, 1.25 and 2.5 mg/kg/30 min. The second group (n = 5) received a
doxapram loading dose of 5.5 mg/kg followed by a maintenance dose of 1 mg/kg/h and incremental doses of
caffeine: 2.5, 5.0, 7.5 and 10.0 mg/kg/30 min. In the first group, ventilation increased after the
caffeine loading dose from 566 +/- 55 to 680 +/- 74 ml/kg/min (plasma
caffeine = 14.7 +/- 1.6 mg/l) and progressively increased with the addition of incremental doses of
doxapram up to 1,000 +/- 108 ml/kg/min at 2.5 mg/kg of
doxapram (p less than 0.001 compared to baseline and
caffeine loading dose). In contrast, in the second group, the
doxapram loading dose markedly increased ventilation from 582 +/- 50 to 936 +/- 75 (p less than 0.002 and p less than 0.04 compared to
caffeine loading dose) at plasma
doxapram of 5.3 +/- 0.8 mg/l, but incremental doses of
caffeine had no effects. We conclude that
doxapram exerts a brisk and powerful
respiratory stimulant effect and produces an additional dose-dependent ventilatory response when added to
caffeine.