David J. Burchfield

Controlled trial of a single dose of synthetic surfactant at birth in premature infants weighing 500 to 699 grams

In a multicenter, double-blind, placebo-controlled trial conducted at 23 hospitals in the United States, a single prophylactic 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm. Despite stratification at entry by birth weight and gender, by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group. Among infants receiving synthetic surfactant, improvements in oxygen requirements were significant at 2 hours after birth (p = 0.014) and persisted for 3 days (p = 0.001); improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth (p = 0.01) and persisted for 3 days (p = 0.008). Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth (p = 0.622 and 0.083, respectively), but became significant thereafter and persisted for 3 days (p = 0.002). Pneumothorax was reduced by slightly more than half (25 vs 11; p = 0.014); death from respiratory distress syndrome (RDS) was also reduced (26 vs 15; p = 0.046). Overall neonatal mortality, however, was not significantly reduced (58 vs 46; p = 0.102). Other complications of RDS and prematurity were not altered, except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant (2 vs 12; p = 0.006). These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function, incidence of air leak, and death from RDS but not overall mortality. The only safety problem identified was an increase in pulmonary hemorrhage.

One-year follow-up evaluation of 260 premature infants with respiratory distress syndrome and birth weights of 700 to 1350 grams randomized to two rescue doses of synthetic surfactant or air placebo

A multicenter, randomized, double-blind, placebo-controlled trial of synthetic surfactant therapy for premature infants with respiratory distress syndrome (RDS) and birth weights of 700 to 1350 gm demonstrated a reduction in severity of RDS, morbidity, and neonatal and 1-year mortality. Of the 419 infants who were entered in the study, 80% of the surviving infants in both the air placebo group (122) and the synthetic surfactant group (138) returned for the follow-up evaluation at 1-year adjusted age. The only significant difference observed at follow-up was a reduction in the incidence of mild cerebral palsy in the synthetic surfactant group (air placebo group, 8 of 122 (7%); synthetic surfactant group, 3 of 138 (2%); relative risk 0.306; 95% confidence interval 0.094, 0.999). No differences were observed between the air placebo and synthetic surfactant treatment groups with respect to health status of the infants, including the incidence of retinopathy of prematurity and neurodevelopmental delays. The difference in the overall incidence of impairment among the 1-year survivors in the air placebo group (43 of 122 (35%)) and in the synthetic surfactant group (40 of 138 (29%)) was not statistically significant. The results of this 1-year follow-up study show that rescue treatment with synthetic surfactant in infants weighing 700 to 1300 gm is not associated with adverse developmental consequences despite the improvement in survival.

DISTRIBUTION OF mRNA CODING FOR CALCIUM PERMEABLE AND IMPERMEABLE AMPA RECEPTOR SUBUNITS DURING OVINE CNS DEVELOPMENT. |[bull]| 1763

Introduction: Following birth asphyxia, extracellular CNS levels of glutamate or other related excitatory amino acids rise and cause overstimulation of glutamate receptors. This leads to a rise in intracellular calcium which triggers a cascade of events ultimately causing neuronal cell death. The AMPA glutamate receptor has been cloned and consists of four subunits (GluR A-D) that can be expressed in alternatively spliced isoforms termed flip and flop. AMPA receptors are assembled from several subunits. The GluR-B subunit, whether expressed alone or in combination with other subunits, forms ion channels that are calcium impermeable. This unique property of the AMPA receptor places it in a pivotal position with regard to hypoxic-ischemic brain damage.

BOLUS ADMINISTRATION OF BUFFERING AGENTS IMPROVE HEMODYNAMICS DURING HYPOXIC LACTIC ACIDOSIS IN NEWBORN SHEEP. 299

Recent studies report deleterious effects of sodium bicarbonate (BIC) in treatment of hypoxic lactic acidosis and have shown carbicarb (CAR), a CO2 consuming buffer, to be more beneficial. In a previous study we found no differences in hemodynamic effects of BIC, CAR or saline (SAL) when administered slowly over 30 min. to hypoxia-induced lactic acidotic lambs. During resuscitation, buffers are generally administered over a much shorter period. We hypothesized that administering buffers in a rapid injection, as in a resuscitative effort, would improve hemodynamics compared to use of SAL. Six newborn lambs underwent surgical instrumentation for catheter and transducer placement to allow measurements of blood pressure (BP), cardiac output (CO) and stroke volume (SV) and allowed 2 days for recovery. The animals were then intubated and mechanically ventilated. Hypoxia was induced using a mixture of 92% nitrogen and 8% oxygen until pH reached 7.0 and the lactic acid reached 13 mmoles/L. BIC, CAR, or equimolar SAL in equal volumes were administered over two minutes. Each animal underwent three experiments receiving each infusion in a randomized fashion. The animals were then placed in room air and allowed to recover. Hemodynamic measurements prior to the boluses were similar between the three groups. Hemodynamic responses pre and post-bolus are shown in thetable. In the SAL group, hemodynamics tended to continue to deteriorate whereas they improved with either BIC or CAR. We conclude, when administered in a rapid fashion, buffers improve hemodynamics during hypoxic lactic acidosis in newborn lambs. This gives support to the use of buffers in neonatal resuscitation.

DISTRIBUTION OF mRNA CODING FOR AMPA RECEPTOR SUBUNITS DURING OVINE CNS DEVELOPMENT. † 2271

Introduction:. Excitotoxicity, the overstimulation of glutamate receptors by L-glutamate, results in neuronal cell death. The AMPA receptor, one of three major ionotropic glutamate receptors, has been cloned and consists of four subunits (GluR-A, GluR-B, GluR-C, and GluR-D) that are expressed in alternatively spliced isoforms termed flip and flop. AMPA receptors containing predominantly flip isoforms are associated with enhanced responses to L-glutamate. Glutamate receptors are present in both fetal humans and fetal sheep, but not in fetal rodents, the most commonly used animal model for excitotoxicity. Because a large proportion of brain injury occurs before birth, we determined the distribution of AMPA receptor subunits and isoforms in an animal species known to express these receptors prenatally.

EFFECTS OF SMOKING ON OXY- AND CARBOXYHEMOGLOBIN (0 2 Hb%, COHb%) IN THE PREGNANT EWE AND FETUS

Smoking during pregnancy leads to lower birthweights in infants, possibly due to displacement of oxygen from maternal and fetal hemoglobin by carbon monoxide. We measured maternal and fetal O2Hb% and COHb% saturation in 4 pregnant ewes after a single smoke using reference tobacco (T), marijuana (M), or marijuana placebo (p) cigarettes. Femoral artery catheters were implanted into ewes and fetuses at 130 days gestation. At 133-140 days, fetal and maternal O2Hb% and COHb% saturations were determined before, during, and for 24 hr after a continuous 10 min exposure to T, M, or P delivered to the standing ewe through an open-ended tracheal T-tube. The sequence of exposure to T (n=4), M (n=3), and P (n=3) was randomized with >48 hr recovery between exposures. Data (mean±SD) were analyzed by ANOVA and, if p <0.05, a multiple comparison procedure was performed.After the 10 min. smoke, maternal O2Hb% dropped from 94±1 to < 92 ± 1 for 2 hr. Maternal COHb% rose from 2.0 ± 0.5 to a peak of 6.3 ± 2 at 15 min, and slowly returned to baseline by 6 hours. Fetal COHb% dropped from 41 ± 11 to 32 ± 11 and remained depressed for 1 hr after the smoke, thus representing an approximate 20% drop in O2 carrying capacity. Fetal COHb% rose steadily from 4.8 ± 0.5 and did not peak until 3-6 hr after the smoke at 6.1 ± 1.All three smoke-types caused decreases in maternal and fetal O2Hb%. T appeared to raise COHb higher than M or P.We conclude that smoking decreases O2 content in the fetus and speculate that multiple exposures would prolong this O2 deficit. The fetus eliminates carbon monoxide much more slowly than the ewe.

EFFECTS OF SMOKING ON OXY- AND CARBOXYHEMOGLOBIN (02Hb|[percnt]|, COHb|[percnt]|) IN THE PREGNANT EWE AND FETUS

Smoking during pregnancy leads to lower birthweights in infants, possibly due to displacement of oxygen from maternal and fetal hemoglobin by carbon monoxide. We measured maternal and fetal O2Hb% and COHb% saturation in 4 pregnant ewes after a single smoke using reference tobacco (T), marijuana (M), or marijuana placebo (p) cigarettes. Femoral artery catheters were implanted into ewes and fetuses at 130 days gestation. At 133-140 days, fetal and maternal O2Hb% and COHb% saturations were determined before, during, and for 24 hr after a continuous 10 min exposure to T, M, or P delivered to the standing ewe through an open-ended tracheal T-tube. The sequence of exposure to T (n=4), M (n=3), and P (n=3) was randomized with >48 hr recovery between exposures. Data (mean±SD) were analyzed by ANOVA and, if p <0.05, a multiple comparison procedure was performed.After the 10 min. smoke, maternal O2Hb% dropped from 94±1 to < 92 ± 1 for 2 hr. Maternal COHb% rose from 2.0 ± 0.5 to a peak of 6.3 ± 2 at 15 min, and slowly returned to baseline by 6 hours. Fetal COHb% dropped from 41 ± 11 to 32 ± 11 and remained depressed for 1 hr after the smoke, thus representing an approximate 20% drop in O2 carrying capacity. Fetal COHb% rose steadily from 4.8 ± 0.5 and did not peak until 3-6 hr after the smoke at 6.1 ± 1.All three smoke-types caused decreases in maternal and fetal O2Hb%. T appeared to raise COHb higher than M or P.We conclude that smoking decreases O2 content in the fetus and speculate that multiple exposures would prolong this O2 deficit. The fetus eliminates carbon monoxide much more slowly than the ewe.

EFFECTS OF SMOKING ON OXY- AND CARBOXYHEMOGLOBIN (02Hb%, COHb%) IN THE PREGNANT EWE AND FETUS

Smoking during pregnancy leads to lower birthweights in infants, possibly due to displacement of oxygen from maternal and fetal hemoglobin by carbon monoxide. We measured maternal and fetal O2Hb% and COHb% saturation in 4 pregnant ewes after a single smoke using reference tobacco (T), marijuana (M), or marijuana placebo (p) cigarettes. Femoral artery catheters were implanted into ewes and fetuses at 130 days gestation. At 133-140 days, fetal and maternal O2Hb% and COHb% saturations were determined before, during, and for 24 hr after a continuous 10 min exposure to T, M, or P delivered to the standing ewe through an open-ended tracheal T-tube. The sequence of exposure to T (n=4), M (n=3), and P (n=3) was randomized with >48 hr recovery between exposures. Data (mean±SD) were analyzed by ANOVA and, if p <0.05, a multiple comparison procedure was performed.After the 10 min. smoke, maternal O2Hb% dropped from 94±1 to < 92 ± 1 for 2 hr. Maternal COHb% rose from 2.0 ± 0.5 to a peak of 6.3 ± 2 at 15 min, and slowly returned to baseline by 6 hours. Fetal COHb% dropped from 41 ± 11 to 32 ± 11 and remained depressed for 1 hr after the smoke, thus representing an approximate 20% drop in O2 carrying capacity. Fetal COHb% rose steadily from 4.8 ± 0.5 and did not peak until 3-6 hr after the smoke at 6.1 ± 1.All three smoke-types caused decreases in maternal and fetal O2Hb%. T appeared to raise COHb higher than M or P.We conclude that smoking decreases O2 content in the fetus and speculate that multiple exposures would prolong this O2 deficit. The fetus eliminates carbon monoxide much more slowly than the ewe.

1355 CHLAMYDIA TRACHOMATIS (Ct) PNEUMONITIS IN PREMATURE INFANTS

Although Ct is recognized as a common etiologic agent in infant pneumonia, its role in pulmonary infection of premature infants has received little attention. Eight premature high risk babies hospitalized in our intensive care nursery over a 9 month period were documented to have Ct pneumonitis by standard McCoy cell tissue culture of endotracheal tube aspirates (7 patients) or nasopbaryngeal swab (1 patient). All patients had negative CMV urine cultures. Birthweights ranged from 610-2200 g. and gestational ages from 26-34 weeks. Six patients were born vaginally and 2 by Caesarean section. Age ranges at time of Ct isolation was 8-83 days (mean 29 days). All patients were cultured during an acute worsening of their respiratory status; 7 showed acute changes on chest X-ray.Seven patients were treated with erythromycin for 3 weeks; the remaining patient died prior to Ct identification. Five patients died of respiratory failure, 1 patient is at home on oxygen therapy for chronic lung disease and 2 patients have no residual lung disease. During this same time period, there were 8 infants of similar gestational age, birthweight, chronological age and mode of delivery whose endotracheal aspirate culture was negative for Ct. All these infants have survived.Chlamydia trachomatis appears to be associated with severe pulmonary disease in premature infants. Ct pneumonitis should be considered in a premature high risk infant with worsening respiratory status.