To determine 1) the effect of arterial CO2 change on the neonatal cerebral circulation and 2) whether 100% O2 would produce significant decrease in cerebral blood flow (CBF), we studied 24 preterm infants to explain the late (5 min) hyperventilation observed in them during hyperoxia. Of these, 12 were studied before and during inhalation of 2-3% CO2 and 12 before and during the inhalation of 100% O2. We measured CBF by a modification of the venous occlusion plethysmography technique and found that CBF increased 7.8% per Torr alveolar carbon dioxide pressure change and that it decreased 15% with 100% O2. These findings suggest that 1) CO2 is an important regulator of CBF in the perterm infant, 2) CBF-CO2 sensitivity in these infants may be greater than in adult subjects, 3) 100% O2 reduced CBF significantly, and 4) a decrease in CBF during administration of 100% O2 may be at least partially responsible for the increase in ventilation with hyperoxia.

We measured the PCO2 apneic threshold in preterm and term infants. We hypothesized that, compared with adult subjects, the PCO2 apneic threshold in neonates is very close to the eupneic PCO2, likely facilitating the appearance of periodic breathing and apnea. In contrast with adults, who need to be artificially hyperventilated to switch from regular to periodic breathing, neonates do this spontaneously. We therefore measured the apneic threshold as the average alveolar PCO2 (PaCO2) of the last three breaths of regular breathing preceding the first apnea of an epoch of periodic breathing. We also measured the PaCO2 of the first three breaths of regular breathing after the last apnea of the same periodic breathing epoch. In preterm infants, eupneic PaCO2 was 38.6 +/- 1.4 Torr, the preperiodic PaCO2 apneic threshold was 37.3 +/- 1.4 Torr, and the postperiodic PaCO2 was 37.2 +/- 1.4 Torr. In term infants, the eupneic PaCO2 was 39.7 +/- 1.1 Torr, the preperiodic PaCO2 apneic threshold was 38.7 +/- 1.0 Torr, and the postperiodic value was 37.9 +/- 1.2 Torr. This means that the PaCO2 apneic thresholds were 1.3 +/- 0.1 and 1.0 +/- 0.2 Torr below eupneic PaCO2 in preterm and term infants, respectively. The transition from eupneic PaCO2 to PaCO2 apneic threshold preceding periodic breathing was accompanied by a minor and nonsignificant increase in ventilation, primarily related to a slight increase in frequency. The findings suggest that neonates breathe very close to their PCO2 apneic threshold, the overall average eupneic PCO2 being only 1.15 +/- 0.2 Torr (0.95-1.79, 95% confidence interval) above the apneic threshold. This value is much lower than that reported for adult subjects (3.5 +/- 0.4 Torr). We speculate that this closeness of eupneic and apneic PCO2 thresholds confers great vulnerability to the respiratory control system in neonates, because minor oscillations in breathing may bring eupneic PCO2 below threshold, causing apnea.

No abstract

In 19 pentobarbital sodium-anesthetized kittens aged 5-34 days, inspired O2 was reduced from 21 to 6-12%. Respiratory frequency (f) and tidal volume (VT) increased within 30 s. Over 5 min f fell to about 60% below control; VT usually fell but remained above control. Arterial pressure fell in 80% of trials, sometimes before f fell. Arterial CO2 was below control, but raising inspired CO2 to keep expired CO2 at control did not prevent the fall in f and VT. The relation between VT and esophageal pressure or diaphragm electromyogram (EMG) did not change consistently, nor was the ratio of high to low frequencies in the diaphragm EMG altered. Carotid chemoreceptor discharge increased within 15 s, and at 5 min it was much above control. We conclude that the change in the breathing pattern in hypoxia is probably due to the activation of a central mechanism.

We hypothesized that enteral doxapram would effectively treat apnea of prematurity without the appearance of major side effects. Of 16 infants, 10 (BW 1,520 ± 102 g) received doxapram alone and 6 (BW 1,020 ± 35 g) received doxapram plus theophylline. Apneas decreased from 16.7 ± 1.9 to 2.1 ± 0.6 in infants receiving doxapram alone, and from 38.2 ± 4.4 to 7.9 ± 2.2 apneas/24 h in those receiving doxapram plus theophylline. This was associated with an increase in alveolar ventilation, a shift of the ventilatory response to CO₂ to the left, and no change in the immediate ventilatory response to 100% oxygen. Side effects included premature teeth buds corresponding to the lower central incisors, prevalence of occult blood in stool and necrotizing enterocolitis. The findings suggest that doxapram effectively controls apnea when given enterally, but should be used cautiously because of potentially harmful side effects.