Bedford W Bonta

Amelioration of bronchopulmonary dysplasia after vitamin E administration. A preliminary report.

We studied the effect of vitamin E on the development of bronchopulmonary dysplasis in neonates with respiratory-distress syndrome. Twenty infants received vitamin E administered intramuscularly during the acute phase of the syndrome, and 20 infants served as controls. Administration of vitamin E significantly increased the serum vitamin E concentration. Nine vitamin-treated and 13 control patients required supplemental oxygen for longer than 250 hours; all were treated with positive-pressure ventilation and endotracheal continuous distending airway pressure. Six of those 13 controls had x-ray changes consistent with bronchopulmonary dysplasia, and four died. None of the nine vitamin-treated patients had changes characteristic of bronchopulmonary dysplasia (P = 0.046), and all survived. Administration of vitamin E during the acute phase of the respiratory-distress syndrome appears to modify the development of bronchopulmonary dysplasis.

Determination of optimal continuous positive airway pressure for the treatment of IRDS by measurement of esophageal pressure.

We describe a simple and reliable method to determine optimal airway pressure in infants with idiopathic respiratory distress syndrome who require continuous positive airway pressure treatment. Esophageal pressure was monitored in ten infants with IRDS during initial application of CPAP. As the level of CPAP was increased in 2 cm H2O increments, changes in Pes were compared with changes in PaO2. Below optimal airway pressure, Pes as well as PaO2 increased insignificantly. When optimal airway pressure (8.1 +/- 0.8 cm H2O) was applied, there was a marked increase in Pes (3.6 +/- 0.8 cm H2O. p less than 0.001) and PaO2 (39.0 +/- 10.0 mm Hg, p less than 0.01). Further increase in CPAP did not result in any subsequent appreciable increase in Pes while PaO2 decreased slightly and PaCO2 increased. Less than optimal CPAP increases F102 requirements and may increase the associated risk of bronchopulmonary dysplasia, while excessive levels of CPAP may increase the risk of pneumothorax. We suggest that esophageal pressure be monitored routinely to determine the optimal level of CPAP for each infant during the initial application of therapy.

Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia

To investigate the presence of subtle narcotic depression following maternal narcotic analgesia, we have evaluated the effects of naloxone versus placebo in a double-blind parallel group study in 43 normal term newborn infants whose mothers had received routine narcotic analgesia within six hours prior to delivery. Infants were given either an intramuscular injection of 20 microgram/kg naloxone or 0.20 ml/kg placebo after determination of the one-minute Apgar score, and the following measurements were compared: Apgar scores at one and five minutes, capillary blood gas values at one, 60, 120, and 240 minutes, and neurobehavioral assessments at one, 4, and 24 hours. No adverse effects from naloxone were observed. Neither Apgar scores nor capillary blood gas determinations differed significantly between the two groups. Response to sound was significantly higher in the naloxone group at 24 hours. The alertness score was significantly higher for the naloxone group at one and four hours; the general assessment score for the naloxone group was significantly higher at four and 24 hours. Average scores of naloxone and placebo groups were also different at four and 24 hours of age. These data demonstrate that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status, potentially reversible by administration of naloxone shortly following delivery.

Neonatal red cell superoxide dismutase enzyme levels: possible role as a cellular defense mechanism against pulmonary oxygen toxicity.

Summary: Red cell superoxide dismutase (SOD) enzyme activity was determined in 58 cord blood specimens obtained from infants over a range of gestational ages. An inverse relationship between red cell SOD activity and gestational age was demonstrated. Red cell SOD activity showed a progressive fall from 263.1 ± 30.5 units/mg non-hemoglobin protein (NIIP) in infants of less than 29 weeks of gestation to 168.9 ± 21.3 units/mg NHP in infants of more than 36 weeks of gestation (P < 0.05). Infants treated for RDS showed an increase in red cell SOD activity which reached significance at 72 hr when compared to cord blood levels from the same population (P < 0.05). No similar significant difference could be demonstrated in gestational age-matched control subjects over the same time period. However, initial cord blood SOD enzyme levels were lower in premature infants with RDS (229.5 ± 30.6 units/mg NHP) than in premature infants without RDS (264.0 ± 38.0 units/mg NIIP). When infants with RDS were examined for oxygen toxicity and survival, red cell SOD levels were noted to decrease over 24 hr in four of five infants who died, three of whom developed bronchopulmonary dysplasia. In the surviving infants, red cell SOD levels showed a significant increase by 48 hr (P < 0.05). None developed bronchopulmonary dyplasia and all survived.Speculation: Increases in red cell superoxide dismutase activity in response to hyperoxic stress may prevent toxic effects of O2- radicals and oxygen toxicity to the lung.

NALOXONE REVERSAL OF MILD NEUROBEHAVIORAL DEPRESSION IN NORMAL NEWBORNS AFTER ROUTINE OBSTETRICAL ANALGESIA

Narcotic antagonists are generally administered to newborns only if they exhibit evidence of cardiorespiratory depression in the delivery room following maternal narcotic analgesia. To investigate the presence of subtle narcotic depression, we have evaluated the effects of naloxone vs placebo in a double blind parallel group study in 43 normal term newborns whose mothers had received routine narcotic analgesia within 6 hrs prior to delivery. The infants were given an IM injection of 20 μg/kg naloxone after the 1 min Apgar, and the following parameters were compared: Apgar scores at 1 and 5 min., capillary blood gases at 1, 30, 60, 120, and 240 min., and Scanlon neurobehavioral assessments at 1, 4, and 24 hrs. No adverse effects were observed. Neither the Apgar scores nor the blood gases differed significantly between the two groups. The alertness score was significantly higher for the naloxone group at 1 and 4 hrs (p < .05, .05). The general score for the Narcan group was higher at 4 hr (p < .05) and 24 hrs (p < .055). Response to sound was significantly higher in the naloxone group at 24 hrs (p < .05). These data suggeat that maternal narcotic analgesia may produce subtle changes in alertness and general behavior not reflected by Apgar scores or respiratory status. It may be advisable, therefore, to administer naloxone to most infants on a routine basis if birth is within 6 hrs of maternal narcotic administration.

EVIDENCE FOR AMELIORATION OF BRONCHOPULMONARY DYSPLASIA (BPD) FOLLOWING VITAMIN E ADMINISTRATION

BPD is a major cause of morbidity and mortality in infants treated for the respiratory distress syndrome (RDS). We have investigated the effect of Vitamin E (E) (Roche E Injectable) in modifying the development of BPD in infants with RDS. Alternate infants received 20 mg E/kg/day while requiring an FiO2 > 0.40. E treated and control infants matched with respect to wt, gest. age, Apgar score and severity of RDS. Patients living less than 10 days were excluded. E levels were below 0.30 mg% in controls and in treated infants were 0.96 mg% and 2.15 mg% at 24 and 48 hr, respectively. Treated infants received an average of 3 doses (range 1-7). Ten of 16 controls required O2 (> 20%) ± positive pressure respiratory support longer than 250 hr as compared with 5 of 14 in the E group (x2, p < .05). Of the 10 controls in O2 longer than 250 hr, 5 had x-ray changes consistent with BPD during the first month of life and 3 of those 5 died. However, x-rays in the 5 treated patients in O2 longer than 250 hr returned to normal or revealed mild abnormalities not typical of BPD; all of this group survived. X-rays were read without knowledge of E treatment. E treated or controls requiring O2 less than 250 hr did not have x-ray changes typical of BPD. Although the numbers are small, these preliminary data suggest that E administration during the acute phase of therapy for RDS may modify the development of BPD.

1345 RISK OF RESPIRATORY DISTRESS SYNDROME (RDS) FROM VERY LATEST SAMPLING FOR LUNG PHOSPHOLIPID PROFILE (LPP) BEFORE OR AT BIRTH AMONG INFANTS WITH MATERNAL PROM

The very latest amniotic fluid (AF) samples obtained from mothers whose pregnancies were complicated by PROM (67 samples) and gastric aspirates (GA) samples obtained from premature infants admitted to NICU for possible treatment of RDS (166 samples) when indicated were analyzed for surface active phospholipids using two zone, thin-layer liquid chromotography following separation of disaturated to obtain LPPS. Results were obtained during the period 9/79 to 6/84 and compared with clinical and xray evidence of RDS among 233 premature infants studied. The following results indicate the risk of RDS vs LPP results to dateWithin these results, it should be noted that transitional LPPs from AF samples indicated only a 57.1% risk (8/14) while LPPs from GA indicated an 88% risk (22/25)(p< .05 by 2-way ANOVA) suggesting that the closer the profile is performed to birth, the more accurate. Both AF & GA LPPs showed a linear correlation with maturation and gestational age. The more mature the profile the greater the GA with the exception of 6 infants with mature(c) LPPs who developed RDS. Of the 6, none were class A IDMs.Conclusion: Infants who demonstrate LPPs which are transitional or less mature have a > 85% risk of developing RDS. LPP provides a valuable tool in guiding obstetric and neonatal care of infants at risk for respiratory distress syndrome.

TRANSIENT PULMONARY VASCULAR LABILITY (TPVL)-IMPORTANCE OF RECOGNITION AMONG LGA INFANTS AT RISK FOR PERSISTENT FETAL CIRCULATION (PFC)

Infants at risk for development of PFC may require hyperventilation (HV) & muscle relaxation (MR) to improve lung compliance and oxygenation. During the past 4 months (6-10/83), we have identified a separate population of infants who may present initially with symptoms indistinguishable from those infants who develop PFC but who respond to hyperoxia (FIO2 = 1.00) and can be successfully managed with oxygen without the need for HV and MR. We studied 12 infants (BW @ 3997.5, GA @ 40.1), 8 with evidence of perinatal aspiration, and compared their initial response to oxygen with 16 infants (BW @ 3102.5 gm, GA @ 38 wk) who required HV & MR for therapy of PFC this past year. No significant differences were noted in PaO2 response in FIO2 = 0.21 or 0.40 among TPVL or PFC infants. A significant rise in PaO2 was observed among TPVL infants, but not PFC infants, when exposed to FIO2 = 1.00 (250.7 torr vs 86.0 torr, p<.0001). No significant difference in pH or PaCO2 were observed. Avg. hours of oxygen (48.8 vs 273. 7, p<.0001) and average hours of increased pulmonary vascular lability (LI≥5:1)(12.3 vs 87.4 hrs, p<.0001) were significantly different between groups. All infants survived. TPVL appears to present among term or post-term LGA infants who have experienced perinatal factors known to be associated with an increased risk of PFC. Among these infants, endotracheal intubation may be avoided, substantially reducing the risk of morbidity associated with HV & MR usually required among infants with PFC.

VOLUME REPLACEMENT IN INFANTS WITH PERSISTENT FETAL CIRCULATION |[lpar]|PFC|[rpar]| TREATED WITH HYPERVENTILATION |[lpar]|HV|[rpar]| & PAVULON |[lpar]|P|[rpar]|

Effective mechanical ventilation of infants with PFC often requires simultaneous administration of P to improve lung compliance and decrease the risk of air leaks. During the past year, we have studied 18 infants (Pr)(BW @ 3222.8 gm; GA @ 38.4 wks) using CVP catheters and volume replacement (VOL), either as colloid or PRBCs, to maintain CVP>5 torr, Uo> 2 cc/kg/hr and Usg < 1.010 while requiring HV & P for PFC. The controls (C) consisted of 16 infants studied retrospectively (BW @ 3018.8 gm; GA @ 39.3 wks) who required HV & P for PFC. 16/18 Pr survived (88.9%) while only 8/16 C survived (50%, p<.01). Among the C group, survivors (CS) and non-survivors (CNS) were compared separately to Pr with respect to avg. MAP, FIO2, PaCO2, Uo, Usg, CVP, and VOL during each 8 hour interval for 160 hours. Hours of O2, HV and P were similar among groups. Avg. MAP, PaCO2 and Usg measurements were significantly lower among Pr compared to CNS (p <.005,<.005,<.0001), while avg. PaO2 & Uo were significantly higher among Pr compared to CNS (p<.0001,<.0001). Significant differences in VOL were observed, especially during the first 72 hours of P. During the entire study period, CS & CNS received <35% VOL compared to Pr (38.7; 59.7 vs 169.0 cc/kg; p<.005,<.05). Tolazoline was ineffective in both C & Pr except when PaCO2 < 25 torr (3/22, 13.6% treated) and did not improve survival. Use of VOL to compensate for peripheral loss of circulating blood volume during P appears to improve survival among infants c PFC.