Robert E. Schumacher

Effects of two rescue doses of a synthetic surfactant on mortality rate and survival without bronchopulmonary dysplasia in 700- to 1350-gram infants with respiratory distress syndrome

In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.

Molecular and phenotypic variability in the congenital alveolar proteinosis syndrome associated with inherited surfactant protein B deficiency

Congenital alveolar proteinosis (CAP) is an often fatal cause of respiratory failure in term newborn infants, which has been associated with a genetic deficiency of surfactant protein B (SP-B) as a result of a frameshift mutation (121ins2) in a family with three affected siblings. In the index cases the deficiency of SP-B was associated with qualitative and quantitative abnormalities of the surfactant proteins A and C. Immunostaining for lung surfactant proteins and a search for the 121ins2 mutation by restriction enzyme analysis of DNA extracted from paraffin-embedded lung tissue was performed for 7 additional affected infants from 6 families, bringing to 10 the total number of patients with CAP who have been studied. In six infants, the surfactant protein immunostaining pattern was similar to that of the index cases. Of these, three patients were homozygous for the 121ins2 mutation; one was a compound heterozygote with the 121ins2 in one allele and a different mutation in the other; and three patients lacked the mutation in both alleles. One infant had an abundance of SP-B, suggesting phenotypic heterogeneity in CAP. Lung ultrastructural abnormalities, such as a reduced number of lamellar bodies, absent tubular myelin, and basal secretion of surfactant lipids and proteins, suggest a significant derangement of surfactant metabolism. The phenotypic heterogeneity in infants with CAP raises the possibility that variable degrees of SP-B deficiency may be more common than previously suspected.

Extracorporeal membrane oxygenation in term newborns : a prospective cost-benefit analysis

Clinicians reserve ECMO for neonates at >80% predicted mortality risk. The authors hypothesized that ECMO instituted at lower (50%) mortality risk would result in fewer intensive care unit days and a lower hospital cost compared with conventional therapy (including ECMO at high mortality risk). This was a randomized control trial, cost-benefit analysis in an academic newborn intensive care unit. The patients were a prospectively studied, consecutive sample of 41 term neonates with 1) age 24-72 hours, 2) “maximal medical management” for > 6 hours, 3) oxygenation index (OI) values > 25 but < 40. (Severity of illness measured by OI=((mean airway pressure X FiO2 X 100) PaO2)). All eligible patients entered. Thirty-two of 37 survivors were evaluated at 1 year. Intervention occurred when OI = 25. Patients were randomized to ECMO or continued medical management (ECMO possible at OI = 40). Planned primary outcome measures were ICU days and hospital charges. Secondary measures were pulmonary and neurologic outcomes at discharge and 1 year. Twenty-two early ECMO patients, 19 controls, 14/19 met late ECMO criteria. Four patients died (two each group). No statistically significant difference was seen in hospital charges (early ECMO =

Gentamicin Pharmacokinetics in Term Neonates Receiving Extracorporeal Membrane Oxygenation

49,500 versus control=

Treatment of Apnea of Prematurity

53,7000), (95% confidence intervals= -

Lack of Vancomycin-associated Nephrotoxicity in Newborn Infants: A Case-Control Study

3200 to +

Treatment of parenteral nutrition-associated cholestasis with cholecystokinin-octapeptide.

5100 more for controls) or ICU days (early =14 + 5 days versus control=19 + 12 days) (95% CI=- 0.8 to +10 more for controls). At 1 year the early group had a higher mental developmental index score (115 + 11) versus (103 + 18), (p = 0.07). Secondary analyses comparing early, late, and no ECMO showed trends toward decreased use of hospital resources and lower morbidity in the early group. The early use of ECMO does not increase hospital cost or utilization and suggests a lower morbidity rate for patients so treated.

Accuracy of Hospital Administrative Data in Reporting Central Line–Associated Bloodstream Infections in Newborns

Extracorporeal membrane oxygenation (ECMO) may affect the pharmacokinetics of certain drugs. The objectives of this study were to determine (1) the pharmacokinetics of gentamicin in neonates on ECMO and compare them to reported values for a similar patient population not on ECMO, (2) if the pharmacokinetics of gentamicin differ between venous‐venous and venous‐arterial bypass, and (3) if the pharmacokinetics of gentamicin are affected by oxygenator surface area (0.6 m2 vs 0.8 m2 oxygenators). The medical records of 29 term neonates who received gentamicin while on ECMO were reviewed. Data collected included gentamicin dosage, peak and trough serum concentrations determined at steady state, duration of treatment, time on ECMO, daily weights, and pertinent laboratory values. An initial dosage of gentamicin 2.5 mg/kg every 18 hours is suggested for term neonates on ECMO. Dosage adjustments should be based on gentamicin serum concentrations, and modifications may also be required after ECMO.

Effect of very delayed repair of congenital diaphragmatic hernia on survival and extracorporeal life support use

In the last decade, knowledge regarding the neurodevelopment and functional aspects of the respiratory centers during postnatal maturation has increased substantially. However, an increase in such knowledge has not provided a basis for change in practice. The diagnosis of apnea of prematurity (AOP) is one of exclusion. All causes of secondary apnea must be ruled out before initiating treatment for AOP. Treatment will depend on the etiology as well as effectiveness and tolerability of the treatment by the patient. The primary goal of any treatment of AOP is to prevent the frequency of apnea lasting > 20 seconds, and/or those that are shorter, but associated with cyanosis and bradycardia.The clinical management of AOP is not much different today than it was two decades ago, with pharmacologic and nonpharmacologic treatment options remaining the mainstay of therapy. Methylxanthines are still the most widely used pharmacologic agents. Due to the wider therapeutic index of caffeine and ease of once daily administration, it should be the preferred agent. Doxapram, or nonpharmacologic treatment measures such as nasal continuous positive airway pressure, may be considered in infants who are unresponsive to methylxanthine treatment alone. Treatment should be continued until there is complete resolution of apnea, and for some time thereafter. The choice of method for weaning treatment remains one of individual physician preference. Discharge from hospital after apnea requires close monitoring and some infants will require home apnea monitors. The decision to provide a home apnea monitor should be individualized for each patient, depending on the effectiveness of treatment and clinical response.

Improving Care for Neonatal Abstinence Syndrome

Objective. The purpose of this study was to compare the incidence of nephrotoxicity, defined as doubling of baseline serum creatinine concentration, in newborn infants with peak vancomycin serum concentrations ≤40 μg/mL at steady state to infants with peak vancomycin serum concentrations >40 μg/mL. A secondary objective was to correlate concomitant disease states and potentially nephrotoxic drug therapy with rises in serum creatinine in vancomycin recipients. Methods. Newborn infants with culture-provenStaphylococcus aureus or coagulase-negative staphylococcal septicemia who received vancomycin therapy for >3 days between 1985 and 1995 were identified from an existing database and a review of medical record. All 69 patients included in the study had serial serum creatinine determinations, including a baseline value within 48 hours of starting treatment with vancomycin, and serum vancomycin concentrations determined after at least three doses, with peak and trough concentrations determined 1 hour after a 60-minute infusion and 15 to 30 minutes before a dose, respectively. Infants with congenital renal or cardiac anomalies were excluded. Demographic characteristics, vancomycin dosing regimen, serum vancomycin concentrations and sample times, concomitant drug therapy, and disease states were recorded. Patients were divided into group A (peak vancomycin concentration ≤40 μg/mL) and group B (peak vancomycin concentration >40 μg/mL). The change in serum creatinine concentration between the start and end of vancomycin therapy was determined. Nephrotoxicity was identified if serum creatinine doubled at any time from the start to the end of vancomycin therapy. Alternative definitions of nephrotoxicity (any rise in serum creatinine to >0.6 mg/dL or new abnormalities of urine sediment) were used in additional analyses. Results. A total of 69 evaluable patients (gestational age, 28.9 ± 3.0 weeks; birth weight, 1219 ± 516 g) were identified, 61 in group A and 8 in group B. Six patients in group A underwent doubling of serum creatinine concentration during vancomycin therapy, whereas none in group B did so. Serum creatinine doubled to >0.6 mg/dL in only 3 infants (all in group A). Any increase in serum creatinine to >0.6 mg/dL was seen in 10 infants, 9 of whom were in group A. No confounding variable, including previous or concomitant underlying disease states associated with renal dysfunction or treatment with other potentially nephrotoxic agents, were associated with a significant rise in serum creatinine. Conclusion. Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 μg/mL.