Rangasamy Ramanathan

A randomized trial of nasopharyngeal-synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation.

OBJECTIVE:To prospectively compare the incidence of respiratory failure in premature infants randomized to receive either nasopharyngeal continuous positive airway pressure (NPCPAP) or nasopharyngeal-synchronized intermittent mandatory ventilation (NP-SIMV) in the immediate postextubation period.STUDY DESIGN:This is a prospective study of very low birth weight (VLBW) infants randomized at the time of extubation to receive either NPCPAP or NP-SIMV in a university-based level III neonatal intensive care unit. Statistical analysis were performed with the Mann-Whitney U test for continuous and ordinal variables, and with the χ-squared test or Fisher’s exact test for categorical variables.RESULTS:A total of 41 VLBW infants were studied; 19 were in the NPCPAP group, and 22 were in the NP-SIMV group. Respiratory failure after extubation in the NP-SIMV group was significantly lower than in the NPCPAP group (5% vs 37%, respectively) (p = 0.016). No statistically significant differences between groups with regard to demographics, severity of initial illness and associated complications, time to extubation, ventilatory management before extubation, weight, age, or nutritional status at the time of extubation were noted.CONCLUSION: NP-SIMV applied to VLBW infants upon extubation is more effective in preventing respiratory failure than NPCPAP.

Bioactive Transforming Growth Factor-Beta in the Lungs of Extremely Low Birthweight Neonates Predicts the Need for Home Oxygen Supplementation

Transforming growth factor-β (TGF-β) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. In the present study, we used a TGF-β responsive-promoter-luciferase construct in mink lung epithelial cells to quantify levels of biologically active TGF-β (BA-TGF-β) in the endotracheal aspirate (ETA) fluid from 16 extremely low birthweight neonates [6 M/10 F, mean GA 26 weeks (range 23–30), mean BW 774 g (range 555–1,075)]. ETA fluid was obtained on day 1 and then every 4 days up to 32 days. BA-TGF-β levels were low (92 ± 19 pg/ml) in the first 24 h of life and then increased 5- to 10-fold with peak BA-TGF-β levels (400 ± 50 pg/ml) on day 20–25. BA-TGF-β levels were higher in male than female infants (p = 0.0056). Prenatal steroids decreased significantly the amount of BA-TGF-β recovered. High initial levels of BA-TGF-β persisted over time and were predictive of the need for oxygen therapy at home. We conclude that abundant BA- TGF-β is present in the lungs of preterm infants and speculate that it may be involved in inflammatory and repair processes encountered in acute and chronic lung disease.

Pulse oximetry for continuous oxygen monitoring in sick newborn infants

We studied 54 neonates with acute cardiorespiratory illness and 21 infants with bronchopulmonary dysplasia, to evaluate the accuracy of a nonheated pulse oximeter in predicting arterial oxygen saturation (SaO2). We also studied the accuracy of transcutaneous oxygen tension (tcPO2) in estimating arterial oxygen tension (PaO2) in infants with bronchopulmonary dysplasia. We compared pulse oximeter SaO2 with simultaneously measured SaO2 (range 78% to 100%) using a co-oximeter. Over a wide range of values for heart rate, blood pressure, hematocrit, PO2, PCO2, and pH, linear regression analysis revealed a close correlation between in vivo pulse oximeter readings and in vitro SaO2 measurements in patients with acute (r = 0.86, Y = 29.64 + 0.68X) and chronic (r = 0.91, Y = 6.29 + 0.96X) disease. Regression analysis of tcPO2 versus PaO2 showed an r value of 0.76 in infants with bronchopulmonary dysplasia. In these patients the mean difference between pulse oximeter SaO2 and in vitro SaO2 was 2.9% +/- 1.8% (SD), whereas the mean difference between tcPO2 and PaO2 was -14.5 +/- 11.1 mm Hg. Fetal hemoglobin ranged from 4.3% to 95%. We conclude that pulse oximetry is an appropriate alternative to tcPO2 for continuous oxygen monitoring in newborn infants with acute cardiorespiratory illnesses and chronic lung disease.

Multicenter Crossover Study of Automated Control of Inspired Oxygen in Ventilated Preterm Infants

OBJECTIVE: To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (Fio2) adjustment in maintaining arterial oxygen saturation (Spo2) within an intended range for mechanically ventilated preterm infants with frequent episodes of decreased Spo2. METHODS: Thirty-two infants (gestational age [median and interquartile range]: 25 weeks [24–27 weeks]; age: 27 days [17–36 days]) were studied during 2 consecutive 24-hour periods, one with Fio2 adjusted by clinical staff members (manual) and the other by an automated system (automated), in random sequence. RESULTS: Time with Spo2 within the intended range (87%–93%) increased significantly during the automated period, compared with the manual period (40% ± 14% vs 32% ± 13% [mean ± SD]). Times with Spo2 of >93% or >98% were significantly reduced during the automated period (21% ± 20% vs 37% ± 12% and 0.7% vs 5.6% [interquartile ranges: 0.1%–7.2% and 2.7%–11.2%], respectively). Time with Spo2 of <87% increased significantly during the automated period (32% ± 12% vs 23% ± 9%), with more-frequent episodes with Spo2 between 80% and 86%, whereas times with Spo2 of <80% or <75% did not differ between periods. Hourly median Fio2 values throughout the automated period were lower and there were substantially fewer manual Fio2 changes (10 ± 9 vs 112 ± 59 changes per 24 hours; P < .001), compared with the manual period. CONCLUSIONS: In infants with fluctuations in Spo2, automated Fio2 adjustment improved maintenance of the intended Spo2 range led to reduced time with high Spo2 and more-frequent episodes with Spo2 between 80% and 86%.

Two-year outcome of infants weighing 600 grams or less at birth and born 1994 through 1998

OBJECTIVE: To assess the neurologic and developmental outcome at 2 years of age in preterm infants with birth weights 600 g or lower. METHODS: We conducted a retrospective review from January 1994 through December 1998 for placental histopathology, maternal factors, neonatal intensive care unit course, growth, neurologic/special sense status, and development at 2 years of age corrected for prematurity. RESULTS: Of the 104 neonates weighing 600 g or less, 24 survived to nursery discharge (23%). Two infants died of chronic lung disease after discharge, and 21 of the remaining 22 infants (95%) returned for follow‐up. Placental pathology was available for 21 (95%); acute inflammation was present in 67%, and other abnormalities occurred in 76%. Mean birth weight was 537 (430‐600) g, and mean gestational age was 24 (22‐27) weeks. At birth, 55% were below the tenth percentile for birth weight. At nursery discharge and 2 years of age, 94% were below the tenth percentile for weight, length, and head circumference. Nineteen of 21 (90%) infants were abnormal on neurodevelopmental follow‐up. Major problems were cerebral palsy, blindness, gastrostomies, and ventriculoperitoneal shunts. CONCLUSION: Abnormal placental histology was present in all but one infant, suggesting fetal injury before birth. Only eight of 20 infants with chorioamnionitis were diagnosed clinically, and all infants had a complicated course. We found a high incidence of intrauterine growth restriction and an almost universal pattern of impaired postnatal growth with extremely poor neurodevelopmental outcome at 2 years of age. (Obstet Gynecol 2003;101:18‐23.

Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial

Objective:To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants <30 weeks’ gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery.Study Design:Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV.Result:A total of 40% of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12±11 days in NCPAP group compared with 7.5±12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups.Conclusion:NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS.

Lung protective ventilatory strategies in very low birth weight infants.

Respiratory distress syndrome (RDS) is the most common respiratory diagnosis in preterm infants. Surfactant therapy and mechanical ventilation using conventional or high-frequency ventilation have been the standard of care in the management of RDS. Bronchopulmonary dysplasia (BPD) continues to remain as a major morbidity in very low birth weight infants despite these treatments. There is no significant difference in pulmonary outcome when an optimal lung volume strategy is used with conventional or high-frequency ventilation. Lung injury is directly related to the duration of invasive ventilation via the endotracheal tube. Studies using noninvasive ventilation, such as nasal continuous positive airway pressure and noninvasive positive pressure ventilation, have shown to decrease postextubation failures as well as a trend toward reduced risk of BPD. Lung protective ventilatory strategy may involve noninvasive ventilation as a primary therapy or following surfactant administration in very preterm infants with RDS. Initial steps in the management of preterm infants may also include sustained inflation to establish functional residual capacity, followed by noninvasive ventilation to minimize lung injury and subsequent development of BPD.

Effects of metaproterenol on pulmonary mechanics, oxygenation, and ventilation in infants with chronic lung disease

Changes in pulmonary resistance, dynamic compliance, tidal volume, and transcutaneous PO2 and PCO2 after nebulized administration of metaproterenol were evaluated in eight newborn infants (birth weight 650 to 1060 g, gestational age 25 to 28 weeks) with chronic lung disease receiving mechanical ventilation. The infants were monitored continuously before and for 15 minutes after nebulization of metaproterenol during 3 consecutive days at mean age 34 days. There were significant increases in compliance, tidal volume, and tcPO2, and significant decreases in pulmonary resistance and tcPCO2. These data show that bronchospasm contributes significantly to the high pulmonary resistance in preterm infants with chronic lung disease and that metaproterenol is beneficial in the therapy of infants with chronic lung disease requiring mechanical ventilation.

Optimal Ventilatory Strategies and Surfactant to Protect the Preterm Lungs

Invasive ventilation via the endotracheal tube is one of the most common therapeutic interventions performed in preterm infants with respiratory failure. Respiratory distress syndrome (RDS) occurs in about 50% of preterm infants born at less than 30 weeks of gestational age. Mechanical ventilation using conventional or high-frequency ventilation and surfactant therapy have become the standard of care in management of preterm infants with RDS. However, bronchopulmonary dysplasia (BPD) remains as a major morbidity with adverse pulmonary and nonpulmonary outcomes in preterm infants despite these interventions. Ventilator-associated lung injury appears to be related to the duration of invasive ventilation via the endotracheal tube rather than the mode of ventilation. Randomized controlled trials comparing conventional mechanical ventilation and high-frequency ventilation, using ‘optimal ventilatory strategies’, have shown no significant difference in rates of BPD. Use of noninvasive ventilation, such as nasal continuous positive airway pressure and nasal intermittent positive pressure ventilation has shown a significant decrease in postextubation failure as well as reduced incidence of BPD. Optimal ventilatory strategy in preterm infants with RDS may begin in the delivery room with application of sustained inflation to establish functional residual capacity, followed by surfactant therapy and rapid extubation to noninvasive ventilation to decrease the incidence of BPD and improve overall outcome.

Lipopolysaccharide-induced tumor necrosis factor-α and IL-10 production by lung macrophages from preterm and term neonates

Lung injury in preterm neonates with respiratory failure has been attributed to persistent inflammation, which is likely to involve lung macrophages (LM). The study objective was to investigate LM during the first 8 d of life from preterm infants (n = 19), using term infants (n = 11) with respiratory failure as control subjects. LM percentages from mixed-cell suspensions produced from tracheobronchial lavage were calculated. A postnatal increase in the mean LM concentration was demonstrated within the preterm group (p = 0.01), which was greater in comparison to that from the term group (p < 0.01). Regression analyses were significant for direct relationships between LM concentrations and ex vivo lipopolysaccharide-induced tumor necrosis factor-α and IL-10 production (r = 0.93 and r = 0.63, respectively), establishing LM as the source of these cytokines. Comparative analyses demonstrated that the ability of preterm versus term LM to produce tumor necrosis factor-α was nearly identical; in contrast, a trend toward diminished levels of IL-10 expression in the preterm group was observed (p = 0.06). Thus, although studies have shown that LM precursors (i.e. cord blood monocytes) produce less tumor necrosis factor-α in preterm versus term infants, the present data strongly suggest that this relationship does not hold postnatally with respect to terminally differentiated LM in sick neonates. Overall, the data are consistent with a pro-versus antiinflammatory imbalance that may bear functional significance on the pathogenesis of chronic lung disease.