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Biomedical subjects

A A Rosenberg

Publications and source records attributed to A A Rosenberg.

At least 19 recordsLinked to original sources

Effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections in infants.

We conducted a prospective, cohort study at two affiliated level III neonatal intensive care units to evaluate the effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections (CRBSI) in infants. A total of 300 infants (n=150 at each site) were enrolled over a 4-year study period. There was no difference in the rate of CRBSI per 1000 catheter days between the two sites (16.2+/-39 vs. 8.9+/-24, P=0.054, 95% CI-14.8 to 0.13). Infants at site A (closed drug-delivery system) had a higher rate of infectious nosocomial respiratory complications per 100 hospital days than infants at site B (open delivery system) (1.1+/-2.2 vs. 0.5+/-1.5, P=0.009), however, there was no difference in the overall number of confirmed or suspected nosocomial infection events per patient between study sites. Logistic regression revealed that the number of additional peripheral catheters, gestational age and duration of parenteral nutrition all significantly contributed to the risk of developing one or more CRSBI. The closed drug-delivery system failed to reduce the incidence of CRBSI or overall rate of nosocomial infections in premature infants.

Catheters, Indwelling↗

Effects of combined superoxide dismutase and catalase on somatosensory evoked potentials and neuropathologic changes in asphyxiated newborn lambs.

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.

Animals↗

Factors associated with successful epoetin alfa therapy in premature infants.

OBJECTIVE: To determine the impact of two different recombinant human erythropoietin (epoetin alfa) dosing strategies on the number of red blood cell (RBC) transfusions, and explore relationships between specific patient and drug regimen variables with epoetin alfa therapy outcomes. DESIGN: Retrospective cohort study. SETTING: Level III university neonatal intensive care unit. METHODS: Infants who received epoetin alfa therapy three times weekly for more than one week were categorized into two epoetin alfa dosing strategy groups: group A (300-749 units/kg/wk) and group B (750-1200 units/kg/wk). The following patient variables were collected and their relationship to therapy outcomes (corrected reticulocyte count [%], hematocrit [%], and number of RBC transfusions after therapy was started) were evaluated using independent Student's t-test, correlation analysis, and stepwise linear regression: birth weight (kg), gestational age (weeks), postnatal age at therapy onset (days), duration of mechanical ventilation (days), number of RBC transfusions before epoetin alfa therapy, phlebotomy loss (mL/kg), epoetin alfa dosage (units/kg/dose), iron dosage (mg/kg/d), duration of therapy (days), and postconceptional age at therapy discontinuation (weeks). RESULTS: The charts of 44 patients were reviewed. No significant impact on outcome was attributed to overall dosing strategy (group A vs. group B). Linear regression identified postnatal age at therapy onset as a significant contributor to mean hematocrit (R2 = 2 0.116; p = 0.023) and postconceptional age at therapy discontinuation as a significant contributor to number of transfusions during and after epoetin alfa use (R2 = 0.118; p = 0.022). A significant positive correlation was found between weekly mean epoetin alfa dosage and mean reticulocyte count (r = 0.326; p = 0.046), mean iron dosage and mean reticulocyte count (r = 0.439; p = 0.006), and ventilator days and total number of transfusions (r = 0.606; p < 0.001). A significant negative correlation was found between number of transfusions and reticulocyte count (r = -0.367; p = 0.023). CONCLUSIONS: Epoetin alfa dosing strategy, as defined in our study, did not significantly affect the number of transfusions. However, postnatal age at therapy initiation, postconceptional age at therapy discontinuation, mean epoetin alfa dosage, and iron dosage correlate with specific outcomes of epoetin alfa therapy in premature infants.

Anemia, Neonatal↗

Late neurosonographic screening is important to the diagnosis of periventricular leukomalacia and ventricular enlargement in preterm infants.

BACKGROUND: Recent cost-containment strategies suggest limiting screening neurosonograms to the second week of life in premature infants with lower gestational ages (< 30 weeks), birth weights (< 1250 g), or more complicated clinical courses. OBJECTIVE: To determine if such strategies reduce detection of cystic periventricular leukomalacia (cPVL) and persistent ventricular enlargement (pVE)--late sonographic abnormalities highly predictive of adverse neurodevelopment in preterm infants. METHODS: Timing, findings, and number of neurosonograms were reviewed for all survivors born at < or = 32 weeks' gestation at University Hospital, Denver, Colo., between January 1992 and June 1995. RESULTS: Of 236 surviving infants, 61 (26%) were never scanned, and 175 (74%) had a total of 432 scans. Only 106 infants (45%) had a neurosonogram on or after 28 days (timed to detect all cPVL/pVE). Eleven infants (4.7%) had cPVL, and 19 (8%) had pVE. Severity of clinical course did not predict development of cPVL, but was a better predictor of pVE. Initial neurosonograms were normal in 6/11 (55%) with cPVL and 5/19 (26%) with pVE. Screening declined from 86% of infants in 1992 (average 2.54 neurosonograms each), to 64% by 1994-1995 (average of 2.22 neurosonograms each). Infants > 30 weeks' gestation comprised 55 of 61 patients without any neurosonograms (90%), 4 of 11 patients with cPVL (36%), and 4 of 19 patients with pVE (21%). CONCLUSION: Screening neurosonography has declined from 1992 to 1995, particularly in larger premature infants (30-32 weeks' gestation) who remain at risk for cPVL and pVE. Clinical course or results of initial studies do not always predict the development of these late abnormalities. We recommend that one neurosonogram be done at > or = 4 weeks of age in all premature infants < or = 32 weeks' gestation, regardless of birth weight, clinical course, or results of prior studies. An earlier neurosonogram should be obtained for infants < 30 weeks' gestation in the second week of life to detect complications of intracranial hemorrhage.

Birth Weight↗

Longitudinal follow-up of a cohort of newborn infants treated with inhaled nitric oxide for persistent pulmonary hypertension.

OBJECTIVE: To describe the outcome of a group of term newborn infants treated with inhaled nitric oxide for severe persistent pulmonary hypertension. STUDY DESIGN: We performed a prospective longitudinal medical and neurodevelopmental follow-up of 51 infants treated as neonates for persistent pulmonary hypertension of the newborn with inhaled nitric oxide. The original number of treated infants was 87, of whom 25 died in the neonatal period; of 62 infants who survived, 51 were seen at 1 year of age and 33 completed a 2-year evaluation. Statistical analysis used population medians, means, and standard deviations for parameters assessed. Paired t tests and chi-square analysis were used to compare outcomes measured at 1 year with assessment at 2 years for the 32 infants seen at both 1- and 2-year visits. RESULTS: At 1-year follow-up median growth percentiles were 20%, 72.5%, and 50% for weight, length, and occipitofrontal circumference, respectively. Thirteen of 51 infants (25.5%) were < 5th percentile in weight. Nine of 51 infants (17.6%) had feeding problems (need for gastrostomy feeding or gastroesophageal reflux), and 14 (27.5%) had a clinical diagnosis of reactive airways disease. Infant development as measured by the Bayley Scales of Infant Development was 104 +/- 16 for the mental development index and 97 +/- 20 for the psychomotor index. Six of 51 infants (11.8%) were found to have severe neurologic handicaps, defined as a Bayley score on either the mental development or psychomotor index of < 68, abnormal findings on neurologic examination, or both. Fewer children (6.1% vs 15.7%) required supplemental oxygen at 2 years compared with 1 year, and performance on the psychomotor index of the Bayley Scales improved significantly. CONCLUSIONS: One- and 2-year follow-up of a cohort of infants with persistent pulmonary hypertension of the newborn who were treated with inhaled nitric oxide had an 11.8% (1 year) and 12.1% (2-year) rate of severe neurodevelopmental disability. There are ongoing medical problems in these infants including reactive airways disease and slow growth that merit continued close longitudinal follow-up.

Administration, Inhalation↗

Fetal drug therapy.

As prenatal diagnosis has become more sophisticated, avenues for a variety of intrauterine therapies have been opened. Considerable experience has been gained with surgical and pharmacologic approaches. This article provides a review of intrauterine drug therapy aimed at preventing fetal and neonatal disease and treating existing fetal conditions. The future awaits the exciting applications of intrauterine hematopoietic transplants and genetic therapy.

Bone Marrow Transplantation↗

A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). DESIGN AND SETTING: Ten-center randomized masked comparison trial. PATIENTS: Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate. INTERVENTIONS: Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios </=.10) persisted after three doses of the randomized surfactant. PRIMARY OUTCOME MEASURES: Three primary outcome measures of efficacy [the incidence of RDS; the incidence of RDS death; and the incidence of survival without bronchopulmonary dysplasia at 28 days after birth] were compared using linear regression techniques. RESULTS: Of 871 randomized infants, 18 infants did not receive treatment with a study surfactant, and 25 infants did not meet all eligibility criteria. The primary analysis of efficacy was performed in the 846 eligible infants and analysis of safety outcomes in the 853 infants who received study surfactant. Demographic characteristics did not differ between the two treatment groups. Compared with Exosurf, Infasurf treatment resulted in a 62% decrease in the incidence of RDS (Infasurf, 16% vs Exosurf, 42%) and a 70% decrease in RDS death (Infasurf, 1.7% vs Exosurf, 5.4%) but did not increase the incidence of survival without bronchopulmonary dysplasia at 28 days. Treatment with Infasurf resulted in significant improvement in several secondary outcome measures. Infasurf-treated infants had lower average FIO2 (Infasurf, .33 [SEM] vs Exosurf, .42; difference .08; 95% confidence interval [CI], .06 to .11) and average mean airway pressure (Infasurf, 6.0 cm H2O vs Exosurf, 7.1 cm H2O; difference 1.1 cm H2O; 95% CI, .7 to 1.6 cm H2O) for the first 72 hours of life. Crossover surfactant treatment was significantly less frequent in the Infasurf compared with the Exosurf group (Infasurf, 1% vs Exosurf, 6%). Complications (bradycardia, clinical airway obstruction, and transcutaneous arterial desaturation) associated with second and third, but not initial, surfactant treatments were observed more frequently in the Infasurf treatment group. Infasurf-treated infants had significantly less air leak (</=7 days) (Infasurf, 8% vs Exosurf, 14%; adjusted relative risk [ARR] .55; 95% CI, .37 to .81). Severe intraventricular hemorrhage (IVH) (grade 3 and 4) did not differ between the two groups (Infasurf, 11.8% vs Exosurf, 8.3%; ARR 1.41; 95% CI, .94 to 2.09) but total IVH occurred more frequently in Infasurf-treated infants (Infasurf, 39.0% vs Exosurf, 29.9%; ARR, 1.30; 95% CI, 1.08 to 1.57). CONCLUSION: Significant reductions in the incidence of RDS, the severity of early respiratory disease, the incidence of pulmonary air leaks associated with RDS, and the mortality attributable to RDS suggest that Infasurf is a more effective surfactant preparation than Exosurf Neonatal in the prophylaxis of RDS. However, Infasurf prophylaxis as used in this study was also associated with a greater risk of total but not severe IVH.

Age Factors↗

A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS). METHODS: We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques. RESULTS: The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants. CONCLUSION: Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

Bronchopulmonary Dysplasia↗

Cerebral hemodynamics and distribution of left ventricular output during inhalation of nitric oxide.

OBJECTIVES: Inhaled nitric oxide is being utilized as a selective pulmonary vasodilator in the treatment of persistent pulmonary hypertension of the newborn. However, the effects of inhaled nitric oxide on cerebral hemodynamics and distribution of left ventricular output in newborn subjects have not been studied. This study was designed to measure quantitatively the effect of inhaled nitric oxide on the distribution of left ventricular output and on cerebral hemodynamics in a perinatal animal model. DESIGN: Prospective, controlled, experimental study. SETTING: Research laboratory. SUBJECTS: Eight fetal sheep. INTERVENTIONS: Each animal was exposed to three separate study periods: a) mechanical ventilation with low FIO2 (maintaining fetal levels of PaO2); b) inhalation of nitric oxide (20 parts per million) during mechanical ventilation and low FIO2; and c) mechanical ventilation with an FIO2 of 1.0. MEASUREMENTS AND MAIN RESULTS: Left ventricular output and cerebral blood flow were measured with radiolabeled microspheres. Cerebral oxygen delivery and consumption variables were calculated using measurements of arterial and cerebral venous (sagittal sinus) oxygen content. Total left ventricular output did not differ among the three treatment groups: 235 +/- 16 mL/min/kg with hypoxic ventilation; 283 +/- 13 mL/min/kg with nitric oxide inhalation; and 242 +/- 17 mL/min/kg with an FIO2 of 1.0. Lung blood flow increased 2.7-fold with inhaled nitric oxide and 1.6-fold during mechanical ventilation with an FIO2 of 1.0. With a left ventricle microsphere injection, increased lung blood flow is indicative of increased systemic-to-pulmonary shunt across the ductus arteriosus. Whole brain blood flow did not differ between the three groups: 49.6 +/- 6.7 mL/min/100 g with hypoxic ventilation; 46.4 +/- 7.4 mL/min/100 g with nitric oxide inhalation; and 36.4 +/- 3.8 mL/min/100 g with an FIO2 of 1.0. Cerebral oxygen delivery increased during inhalation of an FIO2 of 1.0 when compared with nitric oxide inhalation (p < .007); fractional extraction of oxygen decreased (p < .004 compared with hypoxic ventilation, p < .0005 compared with nitric oxide inhalation). Cerebral oxygen consumption did not differ between the three groups (1.11 +/- 0.12 microns/min/100 g with hypoxic ventilation, 0.95 +/- 0.12 microns/min/100 g with nitric oxide inhalation, and 0.96 +/- 0.08 microns/min/100 g with an FIO2 of 1.0). CONCLUSION: Acute pulmonary vasodilation caused by inhalation of nitric oxide does not change left ventricular output, cerebral blood flow, or cerebral oxygen consumption, despite an increased systemic-to-pulmonary shunt across the ductus arteriosus.

Administration, Inhalation↗

Developmental changes in newborn lamb brain mitochondrial activity and postasphyxial lipid peroxidation.

Previously, our laboratory has demonstrated inhibition of mitochondrial state 3 (ADP-dependent) respiration 5 min after resuscitation from an asphyxial insult in lambs less than 3 days of age. Older lambs were resistant to this transient mitochondrial dysfunction. This study was designed to examine if age-related differences in baseline state 3 mitochondrial respiration, electron transport chain activity, or susceptibility to oxygen free radical-mediated lipid peroxidation were related to the previously observed differences in postasphyxial mitochondrial respiration. Mitochondrial respiration was measured in 24 nonasphyxiated control lambs aged 1-10 days using four different substrates. Electron transport chain activity was assessed in 15 of these lambs, and lipid peroxidation measured as conjugated diene production was measured in 11 of these lambs. These lambs were all ventilated to maintain normal blood gases for a time period equal to the length of the hypoxic insult in asphyxiated lambs (see below), after which samples of brain were removed for isolation of mitochondria. A second group of 11 lambs (seven < or = 3 days of age and four > 3 days of age) were asphyxiated. The insult was a 75-to-90-min episode of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 min of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 min after resuscitation. Postasphyxia electron transport chain activity and lipid peroxidation were measured. All measurements described above were done in both nonsynaptic (primarily glial in origin) and synaptic mitochondria. State 3 mitochondrial respiration varied significantly with age, decreasing by an average of 41.2% +/- 11.1% (mean +/- SEM) from Day 2 to Day 5-6 and then increasing back to levels similar to Day 2 by Day 8-10 in nonsynaptic mitochondria. State 3 respiration in synaptic mitochondria decreased 60.6% +/- 5.2% from Day 2 to Day 5-6 before returning to levels similar to Day 2 by Day 8-10. Resting (nonADP-dependent) state 4 respiration demonstrated similar developmental patterns. Electron transport chain activities did not vary with age in the nonasphyxiated control animals. In addition, an asphyxial insult did not diminish electron transport chain activities in either lambs < or = 3 days old or those > 3 days of age.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

Plasma cysteine concentrations in infants with respiratory distress.

Because factors that predispose infants to persistent pulmonary hypertension of the newborn (PPHN) may cause oxidant stress, which in turn may increase demands for cysteine and glutathione, we investigated the availability of cysteine and its precursors in PPHN and related disorders. Plasma concentrations of four sulfur-containing and two non-sulfur-containing amino acids were measured by gas chromatography-mass spectrometry in blood from infants with PPHN, both those managed conventionally (PPHN group) and those treated with extracorporeal membrane oxygenation, as well as from infants with hyaline membrane disease. Concentrations also were measured in umbilical venous cord blood samples from a healthy control population, in venous plasma from infants receiving only intravenously administered glucose-containing solutions because they had noncardiopulmonary illnesses ("fasted" group), and from otherwise healthy, orally fed infants ("fed" group). The plasma total cyst(e)ine concentration was markedly lower in the three groups (PPHN, PPHN and extracorpeal membrane oxygenation, and hyaline membrane disease) receiving an elevated inspired oxygen concentration (0.6 to 1.0) than in fasted or fed control infants. In contrast, levels of plasma methionine, the other major sulfur amino acid, were low in the three groups receiving an elevated inspired oxygen concentration, as well as in fasted infants. Glycine and serine, two non-sulfur-containing amino acids, had a pattern similar to that of plasma methionine. Thus infants with PPHN and hyaline membrane disease have low plasma total cyst(e)ine levels, an effect that does not appear to result primarily from nutritional deprivation. We speculate that the role of cysteine in bioactivation of nitric oxide and as a precursor of glutathione may be relevant to the pathogenesis and evolution of PPHN and respiratory distress syndrome. Further studies are needed to determine whether increased demands for cysteine exist in these disorders.

Algorithms↗

Prevention of intraventricular hemorrhage in the premature infant.

PIVH remains a significant problem in the care of the preterm infant. Recent technologic advances such as real-time ultrasonography and Doppler flow studies have facilitated accurate diagnosis and provided insight into the pathogenesis. Although the overall incidence of PIVH is declining, the outcome of survivors of PIVH--especially those with more severe grades--remains unfavorable. Several antenatal and postnatal interventions aimed at reducing the overall incidence and severity of PIVH have been attempted. Antenatal interventions, in particular phenobarbital, appear to be promising because a substantial percentage of PIVH occurs in the immediate perinatal period. It is significant that the four reported antenatal phenobarbital trials demonstrated a consistent decrease in severe PIVH. Despite the fact that these studies have different designs and each must be considered on its own, the consistency of results makes a strong statement regarding efficacy and safety. The on-going multicenter Neonatal Network trial should provide definitive results as to the efficacy and safety of antenatal phenobarbital in the prevention of PIVH.

Animals↗

Elevated immunoreactive endothelin-1 levels in newborn infants with persistent pulmonary hypertension.

To study the potential role of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, in the pathophysiology of persistent pulmonary hypertension of the newborn (PPHN), we measured arterial concentrations of immunoreactive endothelin-1 (irET-1) in 24 neonates with PPHN. Secondary diagnoses included meconium aspiration syndrome (13 patients), sepsis (2), congenital diaphragmatic hernia (1), asphyxia (1), pulmonary hemorrhage (1), aspiration of blood (1), and respiratory distress syndrome (1). Compared with irET-1 levels in umbilical cord blood in normal infants (15.1 +/- 4.1 pg/ml; mean +/- SEM) and in newborn infants with hyaline membrane disease who were supported by mechanical ventilation (11.8 +/- 1.2 pg/ml), infants with PPHN had markedly elevated circulating irET-1 levels (27.6 +/- 3.6 pg/ml; p < 0.01 vs cord blood, hyaline membrane disease). Infants with severe PPHN requiring extracorporeal membrane oxygenation (ECMO) therapy had higher irET-1 levels than infants with milder disease (31.0 +/- 4.7 for ECMO-treated infants vs 21.2 +/- 2.0 for non-ECMO-treated infants; p < 0.05). In patients treated without ECMO, irET-1 progressively decreased during the following 3 to 5 days, paralleling clinical improvement. In contrast, irET-1 concentrations remained elevated in infants with severe PPHN during ECMO therapy. We conclude that circulating irET-1 levels are elevated in newborn infants with PPHN, are positively correlated with disease severity, and decline with resolution of disease in patients who do not require ECMO therapy. Whether endothelin-1 contributes directly to the pathophysiology of PPHN or is simply a marker of disease activity remains speculative.

Analysis of Variance↗

Failure of tracheal aspirate cultures to define the cause of respiratory deteriorations in neonates.

The spectrum of organisms responsible for lower respiratory tract infection in chronically ventilated neonates is poorly defined. During an 18-month period 63 infants with a respiratory deterioration defined as an increase in fractional inspired O2 concentration > or = 20% and/or mean airway pressure > or = 3 cm H2O were evaluated for pulmonary infection. These infants were compared with 58 stable control ventilated infants. Tracheal aspirates for culture and Gram stain were taken from both groups and were cultured for bacteria, viruses, Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis. In addition each infant had complete blood counts with differential and chest roentgenograms evaluated. Positive tracheal aspirates defined as a heavy growth of a single or two bacterial organisms, and/or any growth of virus, Chlamydia and U. urealyticum were found in 23 of 63 study patients and 20 of 58 controls (P > 0.05). The most frequent isolate in both groups was U. urealyticum. Chest radiographs were positive (new changes, particularly atelectasis and infiltrates) more frequently in the study group than in controls, but complete blood count and tracheal aspirate Gram-stained smears were not helpful in discerning colonization from infection. We conclude that positive tracheal aspirates occur with equal frequency among infants with a clinical suspicion of lower respiratory tract infection and in "well" controls. Chest roentgenogram may be a useful adjunctive test to discriminate between colonization and lower respiratory tract infection.

Cytodiagnosis↗

Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation.

To determine the hemodynamic effects of exogenous nitric oxide (NO) on the immature pulmonary circulation, we studied the response to NO inhalation in 19 mechanically ventilated late-gestation ovine fetuses in three separate protocols. In protocol 1, we examined the relative effects of 1) mechanical ventilation while maintaining fetal arterial O2 tension (PaO2) constant [fractional inspired O2 concentration (FIO2) less than 0.10)], 2) NO inhalation [5-20 parts per million (ppm)] at fetal PaO2, and 3) high FIO2 (1.00) (n = 7). NO increased left pulmonary artery blood flow (Qlpa) in a dose-dependent fashion, from 254 +/- 62 (baseline) to 398 +/- 49 ml/min with 20 ppm NO (P less than 0.001). The response of Qlpa to a FIO2 equal to 1.00 was not different from NO alone. Systemic arterial pressure was not affected by NO. In protocol 2 we studied the effects of prolonged NO inhalation (2 h, 20 ppm) during mechanical ventilation with low FIO2 (n = 4). NO increased Qlpa from 267 +/- 92 to 468 +/- 75 ml/min at 10 min of NO inhalation (P less than 0.001). The increase in Qlpa was sustained during the entire 2-h study period. In protocol 3 we measured left ventricular output (LVO), systemic vascular resistance (SVR), and ductus arteriosus shunting using radiolabeled microspheres (n = 8) during baseline mechanical ventilation and 20 ppm NO inhalation. LVO and SVR were not significantly different in the two study periods; however, the percentage of LVO that reached the lungs (predominantly left-to-right shunting across the ductus arteriosus) increased from 18 +/- 5 to 43 +/- 4% during NO inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

The effect of extracorporeal membrane oxygenation on coronary perfusion and regional blood flow distribution.

We studied the distribution of systemic blood flow during venoarterial extracorporeal membrane oxygenation (ECMO) in newborn lambs. We used a three-compartment model that defined partitioning of blood flow to the heart, upper body (brachiocephalic trunk), and lower body (descending aorta). The method used concurrent left ventricular and arterial cannular injections of radiolabeled microspheres to calculate compartment flows and solve the system of equations that defined the partition model. Seven newborn lambs (1-8 d) were studied. A baseline microsphere injection (left ventricle) was performed and the animals were then placed on venoarterial ECMO using right carotid and jugular vein cannulation. The arterial cannula was placed 2-3.5 cm above the aortic valve. After stabilization on ECMO flow rates of 50 and 100 mL/min/kg, differently labeled microspheres were injected simultaneously into the left ventricle and arterial limb of the ECMO circuit. From the flow partition model, distribution of blood flow was calculated. We found that ECMO did not change the overall distribution of blood flow to the three compartments studied. However, blood flow from the ECMO circuit was preferentially directed to the upper body. Coronary arterial and abdominal organ blood flow was predominantly derived from the left ventricle at both ECMO flow rates. Coronary arterial blood flow did not significantly change on ECMO (253 +/- 45 mL/min/100 g at 50 mL/min/kg ECMO flow; 246 +/- 50 mL/min/100 g at 100 mL/min/kg ECMO flow) compared to baseline (186 +/- 31 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗