I Mark Hiatt

Intermittent phototherapy in the treatment of jaundice in the premature infant

A controlled trial of the use of intermittent phototherapy for the treatment of hyperbilirubinemia in newborn infants is reported. Periods of illumination of (1) 15 minutes light on, 15 minutes light off, (2) 15 minutes on, 30 minutes off, and (3) 15 minutes on, 60 minutes off are as effective as is continuous illumination. A comparison with previous trials of intermittent phototherapy is made and differences in results are explained using as a model the action of light on bilirubin.

1769 THE EFFECT OF FUROSEMIDE ON COMPLIANCE (CDYN) IN ACUTE AND CHRONIC PULMONARY FAILURE

Furosemide was effective in improving Cdyn in a group of pre-term infants suffering from respiratory distress syndrome (RDS) during the first week of life, but had no effect on another group with bronchopulmonary dysplasia (BPD) studied at a later age. Eight infants (BW 1530+/−500g, GA 32+/−2wks) with RDS were studies at 2+/−1 day of age, and eight (BW 840+/−390g, GA 29+/−3 wks) with BPD at 35+/−25 days. Cdyn and PO2 were measured immediately prior to the intravenous infusion of furosemide 1mg/kg and again 20 minutes post infusion. Eight infants (BW 1570+/−520g, GA 32+/−2wks) served as RDS controls, evaluated on day 3+/−2 without furosemide. The results are noted below:The rise in Cdyn in the RDS group was significantly greater than the responses in both control and BPD infants. In this group of infants furosemide was effective in improving compliance in infants with respiratory failure in the early course of RDS but was ineffective in the later complication of BPD.

420 THE COURSE OF HYPERBILIRUBINEMIA IN THE VERY LOW BIRTHWEIGHT INFANT TREATED WITH PHENOBARBITAL

We examined the effect of early phenobarbital therapy on the course of jaundice in 58 infants below 1500g. The study group of 28 infants (BW 1149+/-251g, GA 29.5+7-2.7wks), was treated with a phenobarbital loading dose of 20mg/kg/day at 4.2+/7-3.6 hrs of age, followed by a maintenance dose of 5mg/kg/day for one week. Thirty infants served as controls. Seventeen study and 20 control infants suffered from intraventricular hemorrhage.The results of the comparison showed that treated infants had lower peak serum bilirubin concentrations (7.9+/-1.7 vs 8.6+/7-2.2mg/dl), reached peak SBC levels earlier (92.5+/-50.7 vs 138.0+7-101.1 hrs) and spent less time on phototherapy (5.5+7-2.9 vs 7.5+/-3.S days). In the study group, although peak SBC was similar to that of no IVH infants, the IVH subgroup reached peak SBC later (112.8+/-53.0 vs 61.2+7-25.6 hrs) and spent more time on phototherapy (6.9+7-2.3 vs 3.2+/-2.4 days). Control IVH infants showed similar results with an age at peak of 150.0+7-100.3 vs 114.1+/-101.4 hrs and a duration of phototherapy of 8.8+7-3.7 vs 4.8+7-2.5 days when compared to control infants without IVH.In this group of infants P was effective in reducing the severity of hyperbilirubinemia as indicated by the decreased need for therapy. In addition, the presence of IVH contributed to the hyperbilirubinemia in both treated and control infants.

1799 THE EFFECT OF NALOXONE ON APNEA OF PREMATURITY

Naloxone therapy improved the pneumocardiogram (PCG) results of seven preterm infants suffering from apnea of prematurity. The patients (BW 1.5+/−0.2 kg, GA 32+/−2 weeks), were evaluated with a six hour PCG at 1.0+/−0.7 weeks of age. A single intravenous dose of naloxone, 0.01mg/kg, was administered, and then followed by a second six hour PCG. All PCGs were read by a computerized analyzer (Medical Graphics). The results of the comparison are shown below:The PCG following naloxone administration had fewer short (< 15 sec) and long apneas (>15 sec), decreased apnea density and percent periodic breathing. Naloxone did not influence number, length, or nadir of associated bradycardias. Naloxone therapy was effective in decreasing the severity of clinical apnea in this group of infants.

1472 THE EFFECT OF PRENATAL LIDOCAINE ON HEARING RESPONSES IN TERM INFANTS

Abnormal hearing responses were found in a group of term infants born by Caesarian section after maternal administration of epidural anesthesia in a study comparing the effect of lidocaine and lidocaine-epinephrine combination on the infants neurobe-havioral response. Twenty-nine infants born after lidocaine anesthesia (mean dose 455±85mg) had an umbilical artery lidocaine level of 1.18±0.50ug/ml, and umbilical venous concentration of 1.87±0.70ug/ml compared to 14 born after lidocaine epinephrine (mean dose 406±86mg) that resulted in a UV level of 1.43±0.40ug/ ml and a UA level of 1.06±0.30 ug/ml. All infants were evaluated with the neurobehavioral index (ENNS) at four and 24 hours of age.Both groups demonstrated optimal responses during both time periods in muscle tone and reflex items including pinprick, pull to sit, arm recoil, truncal tone, body tone, rooting, suck, Moro, placing, and alerting. However, response to sound was abnormal in 65% of the lidocaine and 68% of the combined therapy group, comparable to similar results following 0.5% bupivacaine.The results of this study suggest that maternal anesthesia with these agents adversely affects hearing in the newborn infant, possible mechanisms including conduction delay in the eighth nerve or other neuronal pathways.

PHARMACOKINETICS OF NALOXONE IN PREMATURE INFANTS

Rapid disappearance of naloxone was observed in a group of very low birthweight infants examined for naloxone kinetics. Five infants (BW 1.20±0.25kg, GA 29±1wk) received 0.04 mg/per kg of naloxone intravenously, four within the first week of life and one on day 26. Serial serum samples were obtained at specific time intervals and frozen for subsequent analysis. Serum naloxone concentrations were measured by the radioimmunoassay method of Berkowitz (1975).Serial naloxone concentration at 5 min. was 51.5±13.4pmole/ml, at 15 min. 36.7±4.0pmole/ml, at 30 min. 28.9±5.1 pmole/ml, at 60 min. 20.4±5.9pmole/ml, at 120 min. 7.3±2.4pmole/ml, and 240 min. 1.5±0.4pmole/ml. No naloxone was detected at the next sample time (12hrs). The elimination rate constant (Ke) calculated from the decay portion of the elimination curve was 0.823±0.130/hr. The calculated half life (t½) was 51.8±9.2min. No correlations were found between Ke and t½ and initial serum level, birthweight, gestational age, and postnatal age.This group of infants demonstrated rapid elimination of intravenous naloxone, consistent with results obtained in adults.

1401 DERMAL BILIRUBIN KINETICS UNDER BLUE AND GREEN LIGHT

We investigated the efficacy of green light phototherapy in reducing dermal bilirubin concentrations with the transcutaneous bilirubinometer (TcB). Nine infants (BW 3375±370gms)were treated with green light at a mean age of 55±20 hrs, and five controls (3210±530gms) were exposed to blue light at 73±28 hrs. The intensity of the green (13.5±0.8uw/cm2/nm) and blue (12.8±0.1uw/cm2/nm) lights were comparable. An opaque patch covered a 2.5 cm. area of skin, the source for TcB control values. Seventeen simultaneous measurements were recorded from patched and exposed areas every 15 minutes over a period of four hours and rate of TcB change was calculated for each hour of phototherapy.In both light groups TcB remained unchanged under the skin patch over the four hour period. Data from exposed skin showed that the rate of TcB change in the blue light group was -3.3 in the first, -1.6 in the second, -0.4 in the third, and -0.3 TcB units/hr in the fourth hour. In the green light group this change was -1.9, -1.4, -0.8, and -0.4 TcBU/hr in the respective time periods. At the end of the four hours the absolute decrease was comparable in both groups. These results suggest that these lights are equally effective in reducing dermal bilirubin levels, but may differ in their mode of action.

1400 FREQUENCY AND TIDAL VOLUME CHANGES IN HIGH RISK IN FANTS IN RESPONSE TO INHALED CARBON DIOXIDE

We examined the ventilatory response to carbon dioxide in 58 infants at risk for disturbances of ventilatory control. Eight siblings (BW 3285±410g) were tested at 11.6±14.0 weeks, 25 near-miss infants (BW 3220±680g) at 13.0±12.0 wks., 10 preterm infants (BW 1780±750g) with prolonged apnea at 14.3±10.8 wks., 9 term infants (BW 3120 ±81.0g) with cyanosis at 6.2±6.0 wks., and six infants (BW 3370±820g) with reflux at 12.0±7 wks. The responses from baseline (B) to 4% carbon dioxide are shown below:There were no differences in the Ve changes among the groups, however, the frequency response was significantly decreased in the sibling and cyanotic infants. These results point to the heterogeneity of infants at risk for abnormalities of ventilatory control, whereby different mechanisms may be responsible for responses to physiologic stimuli.

1800 THE VENTILATORY RESPONSE TO CARBON DIOXIDE IN HIGH RISK INFANTS

We examined the ventilatory response to CO2 in 123 infants tested with a computerized CO2 waveform analyzer measuring breath by breath responses. Seven SIDS siblings (BW 3.43+/−1.04 kg) were tested at 49.1+/−15.3 weeks post-conceptual age, 19 near-miss infants (2.84+/−0.88 kg) at 60.1+/−14.9 wks, 21 term infants with cyanosis (3.43+/−0.66 kg) at 41.0+/−1.2 wks, 43 preterm infants with apnea (1.56+/−0.31 kg) at 41.9+/−5.0 wks, 18 infants with IVH (1.16+/−0.3 kg) at 46.5+/−12.9 wks, 8 with BPD (1.4+/−0.9 kg) at 48.8+/−12.6 wks, 5 with reflux (2.43+/−0.6 kg) at 43.0+/−7.0 wks, and 5 controls (3.8+/−0.8 kg) at 39.0+/−1.0 wks.The slope of the CO2 response curve was 19.4+/−7.6 among siblings, 25.5+/−17.4 among near-miss, 30.2+/−16.4 among cyanotic, 33.0+/−19.0 in the apneic, 31.5+/−16.8 in the IVH, 28.3+/−19.2 in the BPD, 19.9+/−11.7 in the reflux, and 26.0+/−17.0 mm/kg/min/ mmHg BTPS in the control group. The highest proportion of abnormal slopes (<20 mm/kg/min/mmHg BTPS) were in the reflux (71%), near miss (44%), and sibling (40%) groups. The sibling and reflux groups also showed the lowest increase in minute ventilation (50–55%) compared to the other groups (90–140%) from baseline to 6% CO2. The sibling, near-miss, and reflux groups demonstrated blunted responses to CO2 and are deemed to be at highest risk by this test.

1341 VISUAL INFORMATION PROCESSING IN INFANTS WITH INTRAVENTRICULAR HEMORRHAGE (IVH)

We assessed visual attention in an habituation/recovery paradigm and performance on the Bayley Scales of Infant Development in the second year of life among twelve patients who suffered moderate (Grades II-III) or severe (Grade IV) IVH, either unilateral or bilateral.Test results showed that patients with unilateral bleed had greater habituation to a redundant stimulus, indicating more efficient information processing. Recovery of attention to a novel stimulus appeared to be related to the severity, rather than the laterality, of the IVH. As measured by the Bayley Psychomotor Index (PDI), patients with unilateral bleeds performed better than those with bilateral involvement (mean 85 vs 66). The PDI was unaffected by the grade of IVH. The Bayley Mental Development Index (MDI) was affected by severity level, with higher IVH grades showing poorer performance (mean 71 vs 56).The results of the study support the hypothesis that unilateral hemorrhage results in a more optimal development than a bilateral one, and this may be independent of the grade of the bleed.