Biomedical subjects
Publications and source records attributed to S Abbasi.
Ophthalmic administration of phenylephrine caused decreased pulmonary compliance, tidal volume, and peak airflow values in infants with bronchopulmonary dysplasia but not in control infants. The alpha-adrenergic effects of phenylephrine may aggravate the bronchospastic component of bronchopulmonary dysplasia.
Pulmonary mechanics and energetics were determined in 32 neonates with respiratory distress syndrome, who were randomly assigned to receive treatment with an exogenous synthetic surfactant, Exosurf Neonatal, or air placebo. Pulmonary mechanics were measured before and 2 hours after surfactant (n = 13) or air placebo (n = 19) treatment, then longitudinally at 24, 48, and 72 hours after treatment, and again at 7, 14, and 28 days of age. There were no significant differences in the values for pulmonary mechanics or energetics 2 hours after the first dose of surfactant. Improvement in pulmonary mechanics was apparent 24 hours after surfactant treatment, when dynamic compliance was 36% greater than in the placebo group (p less than 0.03). Lung compliance values were also higher in surfactant-treated infants 48 and 72 hours after treatment, with a maximal increase of 64% at 7 days of age (p less than 0.03). Surfactant treatment also caused a significant decrease in total pulmonary resistance at 48 and 72 hours after initial treatment and at 14 days of age (p less than 0.04). Similarly, a decrease in flow-resistive work of breathing was demonstrated 24, 48, and 72 hours after surfactant treatment. At 28 days of age, pulmonary mechanics were not different in the two groups. We conclude that beneficial effects of surfactant on pulmonary mechanics were not apparent 2 hours after dosing but were evident 24 hours after dosing and persisted for the first 7 to 14 days of life.
We studied 143 low birth weight infants (less than or equal to 1500 gm) with respiratory distress syndrome who required mechanical ventilation, and determined the efficacy of using the alterations in pulmonary mechanics (measured at 1 to 3 days, 4 to 7 days, 2 weeks, and 4 weeks) as possible predictors for the subsequent diagnosis of bronchopulmonary dysplasia (BPD). The sensitivity and specificity of pulmonary compliance and resistance as predictors of BPD were ascertained by logistic regression correlation (p less than 0.01) and receiver operating characteristic curves. With these pulmonary mechanics data and logistic discriminant analysis techniques, we developed BPD prediction models based on pulmonary mechanics, measured between 4 and 7 days of age, to define the likelihood ratio for the subsequent diagnosis of BPD. Eight different BPD prediction models were developed by using combinations of four vectors (pulmonary compliance, total pulmonary resistance, birth weight, gestational age), and each model was validated in a subsequent low birth weight study population (n = 53). All models were deemed accurate for negative prediction of BPD. The models dependent on gestational age and dynamic pulmonary compliance had the highest positive predictive accuracy. The predictive impact of total pulmonary resistance appeared to be minimal. These prediction models may be used to calculate the likelihood ratio for a subsequent BPD diagnosis and thereby objectively categorize both the risk and the magnitude of acute lung injury by the first week of life.
The hypothesis that both perinatal events and stage of retinal development are important factors in determining the age at onset of retinopathy of prematurity (ROP) was tested by comparing gestational age at birth with postnatal and postconceptional age when ROP (using ICROP) was first seen. The study population consisted of 207 infants (111 placebo (P) treated, 96 vitamin E (E) treated) who developed ROP among a group of 914 premature infants (460 P, 454 E) enrolled in a randomised clinical trial of the effect of prophylactic use of vitamin E at pharmacological serum levels on incidence and severity of retinopathy. The mean postnatal age at onset of retinopathy was delayed in E treated infants compared with P treated infants by 1.4 weeks (t = 4.004, p < 0.0001). For both P and E treated infants postnatal age at onset of ROP (which reflects the state of retinal development at which birth insults occur) and postconceptional age at onset of ROP which defines state of maturity) were correlated with gestational age at birth. This suggests that both the event of premature birth and the extent of retinal development are important in determining when ROP will first be observed.
The clinical and pulmonary function test evidence of abnormal airway function in infants with BPD is now well established. Studies have shown persistence of airway obstruction into childhood and evidence of residual dysfunction into adulthood. Furthermore, preterm neonates who have been mechanically ventilated but do not meet any of the BPD definitions also have residual pulmonary dysfunction during infancy. As an increasing number of very low birth weight infants survive in the surfactant era, care must be taken to note that their airways are likely to be extremely compliant and thereby exceedingly susceptible to airway barotrauma in the neonatal period. The long-term consequences of airway injury could lead to residual abnormal airway function during infancy. It is hoped that barotrauma can be minimized substantially with a reduction in both the magnitude and duration of ventilatory support following surfactant therapy. With the advent of user-friendly commercial pulmonary function testing equipment, most neonatal follow-up services should include a comprehensive pulmonary follow-up ancillary to the existing neurodevelopmental follow-up services and may thereby reduce the severity of respiratory morbidities and the need for hospital readmissions.
The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.
Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.
Pulmonary mechanics and energetics were determined in 33 healthy low birthweight infants (less than 1,500 g, 28-34 weeks gestation) who had never received ventilatory support. Tidal volume, dynamic pulmonary compliance, pulmonary resistance, pressure-volume relationships, and tidal flow-volume measurements were obtained by pneumotachography and the esophageal balloon technique. Standardized data collection and software data analysis by least mean squares technique yielded data at 0.5, 1, 2, and 4 weeks postnatally, as a function of gestational age (less than 30, 30-32, and greater than 32 weeks gestation). Relatively stable values were obtained for tidal volume and minute ventilation (normalized for body weight); these were associated with values of peak-to-peak esophageal pressure significantly (P less than 0.001) increasing from 4.4 +/- 0.3 SEM cmH2O at 0.5 weeks to 8.1 +/- 0.8 SEM cmH2O at 4 weeks of age. Dynamic pulmonary compliance ranged from 2.0 to 2.4 mL/cmH2O in the first 4 weeks of life. When normalized for weight, compliance decreased with age, which may suggest a slower pulmonary maturation as compared to increase of body weight. Mean pulmonary resistance decreased from 62.9 cmH2O/L/s at less than 30 weeks gestation to 32.5 cmH2O/L/s at greater than 32 weeks gestation, 0.5 weeks postnatally. Pulmonary resistance peaked at 2 weeks postnatally (P less than 0.05), at all gestational ages, then decreased. Changes in pulmonary mechanics resulted in increasing resistive work of breathing. Our findings suggest a postnatal retardation of pulmonary and airway growth, relative to gestation maturation. These data can provide an objective base of comparison for data in sick, low birthweight neonates.
Surfactant protein-A (SP-A) was measured in bronchoalveolar lavage (BAL) samples from ventilated neonates in order to study the concentration of SP-A with regard to: 1) high-frequency oscillatory ventilation (HFOV) vs. conventional mechanical ventilation (CMV); 2) the postnatal course and ontogeny of SP-A; and 3) the correlation with measurements of pulmonary function. Patients on HFOV had markedly lower BAL SP-A concentrations on days 1 and 2 compared to those on CMV, which may indicate influence of mode of ventilation on surfactant metabolism. The SP-A concentrations increased postnatally concurrent with resolution of acute respiratory distress syndrome. Finally, there were only weak correlations between BAL SP-A concentration and dynamic lung compliance and oxygen requirement.
This paper presents the results of a 20 year survey of ROP among less than or equal to 2000 g BW infants cared for at Pennsylvania Hospital. It relates changes in perinatal care and nutrition, survival rates, and serial serum E levels with incidence and severity of ROP. It includes our protocol for monitoring E nutrition so as to optimize its effectiveness at physiologic serum levels for prophylaxis for ROP. Also presented are the promising results of our experience with vitamin E at pharmacologic serum levels as a treatment for severe ROP (defined as in the Cryo ROP Trial). These indicate the need for a multicenter trial to assess the effect of pharmacologic Vitamin E therapy as an alternative or supplement to therapy of severe ROP with laser or cryo surgery.
Indomethacin was utilized in 24 pregnancies (31 exposed fetuses) in preterm labor who labored despite intravenous tocolysis. The mean gestational age at the start of indomethacin therapy was 25.1 weeks (+/- 4.4), mean duration of indomethacin therapy was 43.9 days (+/- 31.4), mean gestational age at delivery 33.1 weeks (+/- 3.7). Neonatal follow-up revealed the same incidence of complications in these indomethacin-exposed infants, when they were compared with all other infants born in the same time period and exposed to intravenous tocolytics only when matched for gestational age at delivery.
Placental transfer of vitamin E was investigated from 19 to 35 weeks of gestation by analysis of fetal and maternal blood samples for total tocopherol, total lipids, and fetal red blood cell antioxidant reserves. Fifty-two fetal blood samples were obtained under ultrasonographic guide by percutaneous umbilical blood sampling. Thirteen were from fetuses with gestational age less than or equal to 22 weeks (x serum vitamin E = 0.4 +/- 0.14 mg/dl), 12 were from fetuses at 23-27 weeks gestation (x serum vitamin E = 0.4 +/- 0.21 mg/dl), and 27 were from fetuses with gestational age 28-38 weeks (x serum level = 0.37 +/- 0.18). Total lipid levels ranged from 140 to 216 mg/dl. Maternal plasma vitamin E concentrations correlated significantly with concurrent values in the fetus. There were no significant differences in serum vitamin E levels or vitamin E to total lipid ratio in samples from early, mid, or late gestation in either the mother or fetus. Red blood cell antioxidant reserve on samples from 18 fetuses were grossly abnormal by three different functional assays. On the basis of these data, placental transfer of vitamin E appears to be relatively constant through advancing gestation. Red blood cell antioxidant reserve is uniformly low.
The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.
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Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.
Pulmonary function tests were performed on 36 very low birth weight neonates (birth weight less than or equal to 1000 gm, gestational age less than or equal to 30 weeks, appropriate size for gestational age) from birth until 8 weeks of age. Tidal airflow was measured by means of a pneumotachygraph, and the transpulmonary pressure changes were determined by the esophageal balloon technique. Pulmonary mechanics and energetics were calculated by the least mean square analysis technique at 1/2, 1, 2, 4, 6, and 8 weeks of age. Compliance was lowest at 2 weeks and subsequently increased linearly (at approximately 0.1 ml/cm H2O/wk). When compliance was based on body weight, however, no change was noted with advancing age. Resistance was greatest at 2 weeks and subsequently decreased. The infants maintained a normal minute ventilation with a slightly increased resistive work of breathing. Despite our ability to wean 53% of the infants to room air by 8 weeks, none of them had pulmonary mechanics considered normal for term infants. Infants with and without bronchopulmonary dysplasia (BPD) had similar patterns of pulmonary development. At 8 weeks of age, the pulmonary mechanics in infants with BPD who had been weaned to room air were comparable to those in infants without BPD, an observation that calls into question the rationale for defining BPD at 4 weeks in this population. These data suggest that such pulmonary function profiles provide evidence of persistent lung parenchymal abnormalities.
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Ritodrine hydrochloride was administered over a period of two years to a total of 200 women in premature labor. One hundred sixty-two (81 per cent) of the women carried pregnancy to 35 weeks or longer. To determine the effect of ritodrine on the neonates, the duration and amount of exposure, onset of exposure, and interval between cessation of exposure and delivery were correlated with gestational age, birth weight, Apgar scores, mortality, and the presence of hypoglycemia, hyperbilirubinemia, respiratory distress, and intrauterine growth retardation. Infants exposed for six weeks or more (long-term exposure) were significantly heavier than those exposed for shorter periods (short-term exposure), a difference that was possibly attributable to differences in gestational age at birth. Infants who were exposed as fetuses to ritodrine beginning at 30 weeks' or less gestation needed phototherapy more often than did infants whose fetal exposure began at after 30 weeks' gestation. Neither duration of exposure nor gestational age at birth was a significant factor in hyperbilirubinemia. Of infants delivered at or after 35 weeks' gestation, 32 (20 per cent) experienced early hypoglycemia; and 26 of these (81 per cent) were exposed up to the day of delivery. This outcome differed significantly from that of infants whose exposure stopped at least one week before delivery. In addition, respiratory distress syndrome was more common in those infants exposed up until delivery (34 of 36).(ABSTRACT TRUNCATED AT 250 WORDS)