Tsu F. Yeh

Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: A double-blind, controlled study

To determine whether early (less than or equal to 12 hours) postnatal dexamethasone therapy would facilitate removal of the endotracheal tube and improve outcome in premature infants with severe respiratory distress syndrome, we conducted a double-blind, controlled study of 57 infants whose birth weights were less than 2000 gm. The placebo (n = 29) and treated (n = 28) groups were comparable in birth weight (mean +/- SD: 1273 +/- 323 vs 1318 +/- 359 gm), gestational age (30.1 +/- 2.1 vs 30.8 +/- 2.7 weeks), postnatal age (8.7 +/- 3.1 vs 8.5 +/- 3.1 hours), and pulmonary function at the start of the study. The dose of dexamethasone was 1.0 mg/kg/day for 3 days and then was progressively decreased for 12 days. Infants in the dexamethasone group had significantly higher pulmonary compliance, tidal volume, and minute ventilation, and required lower mean airway pressure for ventilation than infants in the placebo group. The endotracheal tube was successfully removed from more infants in the dexamethasone group (16/28 vs 8/29; p less than 0.025). Nineteen infants (65%) in the placebo group and 11 (39%) in the dexamethasone group (p less than 0.05) had lung injuries. Dexamethasone therapy was associated with a temporary increase in blood pressure and plasma glucose concentration and a delay in somatic growth. We conclude that early postnatal dexamethasone therapy improves pulmonary status, facilitates removal of the endotracheal tube, and minimizes lung injuries in premature infants with severe respiratory distress syndrome.

Intravenous indomethacin therapy in premature infants with persistent ductus arteriosus—a double-blind controlled study

A double-blind controlled trial of intravenous indomethacin therapy was performed using a group of 55 premature infants (27 placebo, 28 indomethacin) with a significant persistent ductus arteriosus. Indomethacin administration at a mean postnatal age of 8.9 days was followed by a significant effect on PDA in 89%; 75% of successes were attributable to indomethacin and 25% to spontaneous effects, an improvement by indomethacin of 86% in infants not undergoing spontaneous improvement. The short-term side effects of indomethacin were transient; urinary output and serum sodium concentration decreased and serum potassium concentration increased. Indomethacin administration was associated with a decreased need for assisted ventilation and a decreased need for surgical closure of PDA. There was no significant difference between the placebo and indomethacin groups in mortality and bronchopulmonary dysplasia morbidity. The infants who developed BPD had higher RDS scores and lower PO2 values, requiring higher FIO2s within four hours of birth than those who did not develop BPD, indicating a more severe underlying pulmonary disability present birth.

Penicillin in Infants Weighing Two Kilograms or Less with Early-Onset Group B Streptococcal Disease

We studied the effect of penicillin on early-onset Group B streptococcal disease over a 52-month period in neonates who were at high risk of infection. Shortly after birth, 1187 neonates weighing 2000 g or less had blood samples taken for cultures and were randomized into an early-treatment group (given intramuscular penicillin G within 60 minutes of birth) or a control group. The incidence of early-onset disease was 20 per 1000 live births (24 of 1187); the number of infants in the early-treatment group who had disease (10 of 589) was similar to that in the control group (14 of 598). The fatality rates were similar in both groups (6 of 10 vs. 8 of 14). Cultures from blood obtained with one hour of birth were positive in 21 of the 24 infants with disease; 22 of the 24 were symptomatic within four hours of birth. Thus, infection was well established before the first hour of postnatal life. At autopsy, gram-positive cocci were seen in lung sections of four infants in whom cultures of blood obtained after treatment had been sterile; this indicates that giving routine antibiotic therapy before culture samples are obtained can obscure bacteriologic diagnosis. We conclude that penicillin given at birth to neonates weighing 2000 g or less does not prevent early-onset streptococcal disease or reduce excess mortality associated with disease.

Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: A pilot study

OBJECTIVE. Budesonide is an inhaled steroid with a strong topical effect but with minimal systemic effects; it has been effectively delivered to animal lungs using surfactant as a vehicle. The purposes of this study were to determine whether early intratracheal instillation of budesonide using surfactant as a vehicle would improve pulmonary status, reduce mortality, and reduce chronic lung disease morbidity. PATIENTS AND METHODS. We conducted a prospective, randomized blind trial in 116 very low birth weight infants (<1500 g) who had severe radiographic respiratory distress syndrome and required mechanical ventilation with fraction of inspired oxygen ≥0.6 shortly after birth: 60 were in the treated group (intratracheal instillation of a mixture of 0.25 mg/kg of budesonide and 100.00 mg/kg of survanta, every 8 hours) and 56 were in the control group (100 mg/kg of survanta only, every 8 hours). The end point assessment was the number of infants who would die or develop chronic lung disease at 36 weeks’ postconceptional age. RESULTS. Infants in the treatment group required significantly lower mean airway pressure on day 1 and day 3 and had significantly lower oxygen index and Pco2 during the first 3 days than infants in the control group. More infants were extubated in the treatment group than controls at 1 and 2 weeks. The combined outcome of deaths or chronic lung disease was significantly lower in the treatment group than in the control group (19 of 60 vs 34 of 56). No clinically significant adverse effects were observed during the study. CONCLUSIONS. This pilot study indicated that early postnatal intratracheal instillation of budesonide using surfactant as vehicle significantly improved the combined outcome of death or chronic lung disease in small premature infants without causing immediate adverse effects. The results are encouraging, and a large sample multicenter trial is warranted.

Furosemide prevents the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus

To determine if furosemide would prevent the renal side effects of indomethacin therapy in premature infants with patent ductus arteriosus, 19 premature infants were randomized into two groups: nine received indomethacin alone, and ten received indomethacin followed immediately by furosemide. There was no significant difference between the groups in birth weight, gestational age, postnatal age, and in cardiopulmonary or renal status at the time of study. Infants who received indomethacin and furosemide had significantly higher urine output (P less than 0.05), higher FENa and FECl (P less than 0.01), and higher glomerular filtration rate (P less than 0.05) than those of infants who received indomethacin alone. Seven infants in each group responded to indomethacin therapy with disappearance of PDA murmur and improvement of cardiovascular status. The results of this study suggest that furosemide may prevent the renal side effects of indomethacin therapy and yet not affect the efficacy of indomethacin in the closure of a PDA.

Hydrocortisone therapy in meconium aspiration syndrome: A controlled study

To evaluate the efficacy of glucocorticoids in the treatment of infants with meconium aspiration syndrome, a double-blind study using hydrocortisone or a lactose placebo was undertaken. Thirty-five infants were included in the study. No significant differences in arterial Po2, Pco2, pH, A-aDo2 gradients, in requirement for assisted ventilation, or in survival were domonstrated between the groups. In control infants, a significant decrease (p less than 0.01) in respiratory distress score was found at 48 to 72 hours of age; in treated infants, it was seen only after 72 hours. The infants in the treated group took a significantly longer (p less than 0.01) period of time to wean to room air than those in the control group (68.9 +/- 9.6 hours vs 36.6 +/- 6.9 hours). On the basis of these observations, hydrocortisone is not recommended for treatment of MAS.

Early Dexamethasone Therapy and Blood Cell Count in Preterm Infants

Objective. To assess the effects of early postnatal dexamethasone therapy on hematologic values in preterm infants. Materials and Methods. We reviewed the hematologic data of 179 preterm infants who participated in a double-blind clinical trial of early postnatal dexamethasone therapy (<12 hours after birth) for the prevention of chronic lung disease. One group (86 infants) received saline and the other group (93 infants) received dexamethasone. Dexamethasone was given intravenously every 12 hours in tapering doses: 0.25 mg/kg on days 1 to 7, 0.12 mg/kg on days 8 to 14, 0.05 mg/kg on days 15 to 21, and 0.02 mg/kg on days 21 to 28. Blood samples were obtained on days 0, 3, 7, 10, 14, 21, and 28. None of the infants received prenatal steroid therapy. Results. Multiple regression analysis revealed significant differences in the values versus time curves of the white blood cell, neutrophil, lymphocyte, basophil, and eosinophil counts between the two groups. The white blood cell count was significantly higher in the dexamethasone group on days 7 through 14, and this was associated with significantly higher numbers of segmented neutrophils and band forms and significantly lower numbers of lymphocytes and eosinophils. The hematocrit and platelet counts were similar in the two groups throughout most of the trial. Except for platelet count, steroid therapy did not alter the hematologic values for infants with bacteremia. Conclusion. Dexamethasone affects white blood cell, segmented neutrophil, lymphocyte, basophil, and eosinophil counts in neonates. This should be taken into consideration when evaluating preterm infants who are receiving dexamethasone. early dexamethasone therapy; neonatal blood count; preterm infant; respiratory distress syndrome.

Retinopathy of prematurity (ROP) and indomethacin therapy in premature infants with paten ductus arterious (PDA)

Recent studies suggested that prostaglandins (PGs) may play a role in the pathogenesis of retinopathy of prematurity (ROP). To evaluate if PGs inhibitor, indomethacin, would affect the incidence or severity of the ROP, an analysis was performed on 47 infants who participated in a double-blind controlled study of indomethacin for the closure of PDA. Twenty-three were in the control group and 24 in the indomethacin group. Indirect ophthalmoscopic examinations were performed from about 4 weeks of postnatal age and onward as needed. There was no significant difference between the groups with respect to birth weight, gestational age, postnatal age, Apgar score, and cardiopulmonary status shortly after birth and at the time of study. Six in the control and 2 in the indomethacin group (p = 0.58) developed active ROP; one in each group developed cicatricial ROP. It appears that with current doses of therapy, indomethacin does not increase the incidence or severity of ROP.

Oxygen consumption and insensible water loss in premature infants in single- versus double-walled incubators

Fifteen studies were performed in ten premature infants whose birth weight (mean +/- SD) was 1,444 +/- 250 gm, gestational age 32.7 +/- 1.0 weeks, and postnatal age 10.7 +/- 3.3 days. Each study consisted of three hours simultaneous measurement of insensible water loss and oxygen consumption under two conditions for the same infant: (1) inside a single-walled incubator and (2) inside a double-walled incubator. The double-walled incubator provided significantly (P < 0.001) higher operative temperature and incubator wall temperature than did the single-walled incubator. Infants inside the double-walled incubator had significantly lower (P < 0.01) IWL (30% reduction) and lower (P < 0.05) VO2 (17% reduction) than inside the single-walled incubator--a net caloric saving of 11.8 kcal/kg/day. This saving of energy expenditure may be important in affecting the growth and outcome of the low-birth-weight infants.

Increased O2 Consumption and Energy Loss in Premature Infants following Medical Care Procedures

Oxygen consumption (VO2) and CO2 production (VCO2) were measured continuously for 24 h in 10 premature infants during their ongoing nursing care. Using a flow-through technique, the total VO2 and VCO2 over a given period of time were determined from the area under the O2-and CO2-concentration-time curve of the mixed expired gas. Following chest physiotherapy, heel stick and i.v. needle insertion, there was a significant (p less than 0.01) increase in VO2 and VCO2. When measured for 24 h, the total daily increase of VO2 attributed to these procedures ranged from 2.1 to 11.7% of total daily VO2, equivalent to an estimated energy loss of 0.6-4.1 kcal/kg/day.