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Objective: The aim of the study was to assess the association of initial lactate (L0) with mortality in children with severe sepsis., Methods: This prospective cohort study included 74 patients younger than 18 years with severe sepsis admitted to the pediatric intensive care unit (PICU) of a tertiary, academic children's hospital with lactate measured within 3 hours of meeting severe sepsis or septic shock. The primary outcome was in-hospital mortality. The secondary outcomes included PICU and hospital length of stay., Results: Although overall mortality was 10.5% (n = 18), patients with L0 measured (n = 72) had a higher mortality (16% vs 6%, P = 0.03) and higher median PRISM-III risk of mortality scores (P = 0.02) than those who did not. Median L0 was no different between nonsurvivors and survivors (3.6 mmol/L [interquartile range, 2.0-9.0] in nonsurvivors vs 2.3 mmol/L [interquartile range, 1.4-3.5] in survivors, P = 0.11). However, L0 was independently associated with PRISM-III score (coefficient, 1.12; 95% confidence interval, 0.4-1.8; P = 0.003) with an increase in mean PRISM-III score of 1.12 U for every 1 mmol/L increase in L0, with L0 accounting for 12% of the variability in PRISM-III scores between patients. There was no association between L0 and PICU or hospital length of stay., Conclusions: Although our single center study did not demonstrate that an elevated early lactate is associated with mortality in pediatric severe sepsis, L0 did correlate strongly with PRISM-III, the most robust measure of mortality risk in pediatrics. Therefore, early lactate measurement may be important as an early biomarker of disease severity. These data should be validated in a larger, multicenter, prospective study.

Objective: To evaluate the relationship between maternal self-reported race/ethnicity and persistent wheezing illness in former high-risk, extremely low gestational age newborns, and to quantify the contribution of socioeconomic, environmental, and biological factors on this relationship., Study Design: We assessed persistent wheezing illness determined at 18-24 months corrected (for prematurity) age in survivors of a randomized trial. Parents/caregivers were surveyed for wheeze and inhaled asthma medication use quarterly to 12 months, and at 18 and 24 months. We used multivariable analysis to evaluate the relationship of maternal race to persistent wheezing illness, and identified mediators for this relationship via formal mediation analysis., Results: Of 420 infants (25.2 ± 1.2 weeks of gestation and 714 ± 166 g at birth, 57% male, 34% maternal black race), 189 (45%) had persistent wheezing illness. After adjustment for gestational age, birth weight, and sex, infants of black mothers had increased odds of persistent wheeze compared with infants of nonblack mothers (OR = 2.9, 95% CI 1.9, 4.5). Only bronchopulmonary dysplasia, breast milk diet, and public insurance status were identified as mediators. In this model, the direct effect of race accounted for 69% of the relationship between maternal race and persistent wheeze, whereas breast milk diet, public insurance status, and bronchopulmonary dysplasia accounted for 8%, 12%, and 10%, respectively., Conclusions: Among former high-risk extremely low gestational age newborns, infants of black mothers have increased odds of developing persistent wheeze. A substantial proportion of this effect is directly accounted for by race, which may reflect unmeasured environmental influences, and acquired and innate biological differences., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of late surfactant on respiratory outcomes determined at 1-year corrected age in the Trial of Late Surfactant (TOLSURF), which randomized newborns of extremely low gestational age (≤28 weeks' gestational age) ventilated at 7-14 days to late surfactant and inhaled nitric oxide vs inhaled nitric oxide-alone (control)., Study Design: Caregivers were surveyed in a double-blinded manner at 3, 6, 9, and 12 months' corrected age to collect information on respiratory resource use (infant medication use, home support, and hospitalization). Infants were classified for composite outcomes of pulmonary morbidity (no PM, determined in infants with no reported respiratory resource use) and persistent PM (determined in infants with any resource use in ≥3 surveys)., Results: Infants (n = 450, late surfactant n = 217, control n = 233) were 25.3 ± 1.2 weeks' gestation and 713 ± 164 g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group (35.8% vs 52.9%, relative benefit [RB] 1.28 [95% CI 1.07-1.55]). There was no benefit of late surfactant for No PM vs PM (RB 1.27; 95% CI 0.89-1.81) or no persistent PM vs persistent PM (RB 1.01; 95% CI 0.87-1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89-1.80) for no PM and RB 1.24 (95% CI 1.08-1.42) for no persistent PM., Conclusion: Treatment of newborns of extremely low gestational age with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death., Study Design: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as the sum of the average daily supplemental oxygen over time periods of interest up to 28 days of age. Area under the receiver operating curve (AUROC) values were generated to evaluate the accuracy of CSO for prediction of BPD or death. The independent relationship between CSO and BPD or death was assessed in multivariate modeling, while adjusting for mean airway pressure., Results: In the study infants, mean gestational age at birth was 25.2 ± 1.2 weeks and mean birth weight was 700 ± 165 g. The AUROC value for CSO at 14 days was significantly better than that at earlier time points for outcome prediction (OR, 0.70; 95% CI, 0.65-0.74); it did not increase with the addition of later data. In multivariate modeling, a CSO increase of 1 at 14 days increased the odds of BPD or death (OR, 1.7; 95% CI, 1.3-2.2; P < .0001), which corresponds to a 7% higher daily supplemental oxygen value., Conclusion: In high-risk extremely low gestational age newborns, the predictive accuracy of CSO plateaus at 14 days. CSO is independently associated with BPD or death. This index may identify infants who could benefit from early intervention to prevent BPD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To predict mortality or length of stay (LOS) >109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH)., Study Design: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born >34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS >109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants., Results: The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS >109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P<0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P<0.001), the receipt of extracorporeal support (OR 8.4, P<0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS >109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ(2), P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ(2), P=0.05)., Conclusions: Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

Objective: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD)., Study Design: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction., Results: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks., Conclusion: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing., Trial Registration: ClinicalTrials.gov: NCT01022580., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes., Study Design: This is a descriptive study evaluating the data collected prospectively in the Children's Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children's hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks' gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010-July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge., Result: High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%., Conclusion: Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Objective: To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC)., Study Design: Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (<28 vs 28(0/7) to 36(6/7) weeks' gestation)., Result: Of the 753 eligible infants, 60% were born at <28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (<28 weeks' gestation: 41%; 28(0/7) to 36(6/7) weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P<0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P<0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (<28 weeks': 5.2%; 28(0/7) to 36(6/7) weeks': 9.9%, P=0.048)., Conclusion: After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born <28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities.

Background/purpose: The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS., Design/methods: We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS., Results: Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p<0.001). This association persisted in the multivariable equation (β=1.35, 95% CI: 1.21, 1.52, p<0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections., Conclusions: In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The Children's Hospitals Neonatal Consortium is a multicenter collaboration of leaders from 27 regional neonatal intensive care units (NICUs) who partnered with the Children's Hospital Association to develop the Children's Hospitals Neonatal Database (CHND), launched in 2010. The purpose of this report is to provide a first summary of the population of infants cared for in these NICUs, including representative diagnoses and short-term outcomes, as well as to characterize the participating NICUs and institutions. During the first 2 1/2 years of data collection, 40910 infants were eligible. Few were born inside these hospitals (2.8%) and the median gestational age at birth was 36 weeks. Surgical intervention (32%) was common; however, mortality (5.6%) was infrequent. Initial queries into diagnosis-specific inter-center variation in care practices and short-term outcomes, including length of stay, showed striking differences. The CHND provides a contemporary, national benchmark of short-term outcomes for infants with uncommon neonatal illnesses. These data will be valuable in counseling families and for conducting observational studies, clinical trials and collaborative quality improvement initiatives.

Background/purpose: Infants with severe chronic lung disease (sCLD) may require surgical procedures to manage their medical problems; however, the scope of these interventions is undefined. The purpose of this study was to characterize the frequency, type, and timing of operative interventions performed in hospitalized infants with sCLD., Methods: The Children's Hospital Neonatal Database was used to identify infants with sCLD from 24 children's hospital's NICUs hospitalized over a recent 16-month period., Results: 556 infants were diagnosed with sCLD; less than 3% of infants had operations prior to referral and 30% were referred for surgical evaluation. In contrast, 71% of all sCLD infants received ≥1 surgical procedure during the CHND NICU hospitalization, with a mean of 3 operations performed per infant. Gastrostomy insertion (24%), fundoplication (11%), herniorrhaphy (13%), and tracheostomy placement (12%) were the most commonly performed operations. The timing of gastrostomy (PMA 48±10 wk) and tracheostomy (PMA 47±7 wk) insertions varied, and for infants who received both devices, only 33% were inserted concurrently (13/40 infants)., Conclusions: A striking majority of infants with sCLD received multiple surgical procedures during hospitalizations at participating NICUs. Further work regarding the timing, coordination, perioperative complications, and clinical outcomes for these infants is warranted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born < 32 weeks' gestation referred to regional neonatal intensive care units., Study Design: We conducted a retrospective cohort study in infants born < 32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support >2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P < 0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants., Result: Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66)., Conclusion: Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

Objectives: To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others., Study Design: Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND)., Results: Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01)., Conclusions: Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD., Methods: We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities., Results: We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration., Conclusions: External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.

Objective: To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units., Study Design: Infants born <32 weeks' gestation with sBPD were identified using the Children's Hospital Neonatal Database. Descriptive outcomes are reported., Result: A total of 867 patients were eligible. On average, infants were born at 26 weeks' gestation and referred 43 days after birth. Infants frequently experienced lung injury (pneumonia: 24.1%; air leak: 9%) and received systemic corticosteroids (61%) and mechanical ventilation (median duration 37 days). Although 91% survived to discharge, the mean post-menstrual age was 47 weeks. Ongoing care such as supplemental oxygen (66%) and tracheostomy (5%) were frequently needed., Conclusion: Referred infants with sBPD sustain multiple insults to lung function and development. Because affected infants have no proven, safe or efficacious therapy and endure an exceptional burden of care even after referral, urgent work is required to observe and improve their outcomes.

Background: Bronchodilator treatment for asthma can be provided with various aerosol-generating devices and methods. There have been no randomized trials of a breath-actuated nebulizer versus continuous 1-hour nebulization and/or small-volume constant-output nebulizer in pediatric asthma patients., Methods: We conducted a randomized study of one-time albuterol treatment with the AeroEclipse breath-actuated nebulizer versus standard therapy (single treatment via small-volume nebulizer or 1-hour of continuous nebulized albuterol) in pediatric asthma patients in the emergency department. Eligible patients were those admitted to the emergency department, 0 months to 18 years of age, who presented with asthma or wheezing. We assessed all the patients with our clinical asthma scoring system and peak-flow measurement if possible. We stratified the patients by clinical asthma score and weight, and then randomized them to receive their initial albuterol treatment in the emergency department via either AeroEclipse or standard therapy. We recorded time in the emergency department, change in clinical asthma score, need for additional bronchodilator treatments, need for admission, patient response, ability to actuate the AeroEclipse, and adverse effects., Results: We enrolled 149 patients between October 14, 2004 and November 11, 2005, and we randomized 84 patients to AeroEclipse and 65 to standard therapy. The cohort's average age was 5.5 years. There were no significant differences in demographics. The initial mean clinical asthma scores were 5.1 ± 2.4 in the AeroEclipse group, and 5.1 ± 2.1 in the standard-therapy group. Time in the emergency department was not different (AeroEclipse 102 min, standard therapy 125 min, P = .10), but the AeroEclipse group had a significantly greater improvement in clinical asthma score (1.9 ± 1.2 vs 1.2 ± 1.4, P = .001) and respiratory rate (P = .002), and significantly lower admission rate (38% vs 57%, P = .03). There was no difference in adverse effects., Conclusions: Although AeroEclipse did not reduce the time in the ED, it significantly improved clinical asthma score, decreased admissions, and decreased respiratory rate.

Both HFOV and HFJV are important adjuncts to the ventilatory care of sick infants and children. Today, it is important that neonatologists, pediatric intensivists, and respiratory care practitioners understand these ventilators and the options they provide. It is no longer necessary to continue the use of damaging pressures and volumes with CV simply because no other option is available. The clinician who understands not only the pathology and physiology of the underlying lung condition but also understands the available choices in ventilators, how each ventilator functions, and what potential advantage it may offer his patients is able to provide the best possible care to these critically ill patients.

Background: Bronchopulmonary dysplasia in premature infants is associated with prolonged hospitalization, as well as abnormal pulmonary and neurodevelopmental outcome. In animal models, inhaled nitric oxide improves both gas exchange and lung structural development, but the use of this therapy in infants at risk for bronchopulmonary dysplasia is controversial., Methods: We conducted a randomized, stratified, double-blind, placebo-controlled trial of inhaled nitric oxide at 21 centers involving infants with a birth weight of 1250 g or less who required ventilatory support between 7 and 21 days of age. Treated infants received decreasing concentrations of nitric oxide, beginning at 20 ppm, for a minimum of 24 days. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age., Results: Among 294 infants receiving nitric oxide and 288 receiving placebo birth weight (766 g and 759 g, respectively), gestational age (26 weeks in both groups), and other characteristics were similar. The rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was 43.9 percent in the group receiving nitric oxide and 36.8 percent in the placebo group (P=0.042). The infants who received inhaled nitric oxide were discharged sooner (P=0.04) and received supplemental oxygen therapy for a shorter time (P=0.006). There were no short-term safety concerns., Conclusions: Inhaled nitric oxide therapy improves the pulmonary outcome for premature infants who are at risk for bronchopulmonary dysplasia when it is started between 7 and 21 days of age and has no apparent short-term adverse effects. (ClinicalTrials.gov number, NCT00000548 [ClinicalTrials.gov] .)., (Copyright 2006 Massachusetts Medical Society.)

Arguably one of the most important advances in critical care medicine in recent years has been the understanding that mechanical ventilators can impart harm and that lung-protective ventilation strategies can save lives. High-frequency oscillatory ventilation appears ideally suited for lung protection at first glance. Two camps of opinion exist, however, even in neonates where this modality has been most extensively studied. In the present debate, the prevailing arguments from each of those camps are made available for the reader to decide.

Objective: To evaluate the feasibility of conducting a prospective, randomized trial comparing early high-frequency oscillatory ventilation (HFOV) to synchronized intermittent mandatory ventilation (SIMV) in very low birth weight (VLBW) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial. Although this pilot study was not powered to detect differences in outcome, we also collected outcome data., Design: Prospective, multicenter, randomized pilot study., Setting: Seven tertiary-level intensive care nurseries with previous experience with both HFOV and flow-triggered SIMV., Patients: Fifty infants weighing 501 to 1200 g, less than 4 hours of age, who had received one dose of surfactant and required ventilation with mean airway pressure > or =6 cm H2O and F(I)O2 > or =0.25, and had an anticipated duration of ventilation greater than 24 hours., Interventions: Patients were stratified by birth weight and prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies, and extubation criteria., Measurements: Data were collected using the tools planned for the larger collaborative study. Protocol compliance was closely monitored, with successive changes in the protocol made as necessary to improve clarity and increase compliance. The incidence of major neonatal adverse outcomes was recorded., Main Results: Data are presented for 24 HFOV and 24 SIMV infants (two infants, twins, were withdrawn from the study at parent's request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived to 36 weeks corrected age. Age at final extubation for survivors was 16+/-16 (mean+/-SD) days for HFOV infants and 24+/-24 days for SIMV infants. At 36 weeks corrected age, 14 of the 19 HFOV survivors were extubated and in room air, whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors were extubated and in room air, whereas 14 required supplemental oxygen. Grade III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV patients. Overall compliance with the ventilator protocols was 82% for the SIMV protocol, and 88% for the HFOV protocol., Conclusions: The preliminary outcome data supports conducting the large randomized trial, which began in July of 1998. The protocols for the ventilator management of VLBW infants, both with HFOV and with SIMV were easily implemented and consistently followed, and are presented here.

Elevated pulmonary vascular resistance is seen in premature infants with severe respiratory distress syndrome (RDS). Inhaled nitric oxide (NO) has been shown to decrease pulmonary vascular resistance and to improve oxygenation in some patients with respiratory failure. The purpose of this study was to determine whether premature infants with severe RDS would respond to inhaled NO with an improvement in oxygenation. Eleven premature infants (mean gestational age 29.8 weeks) with severe respiratory failure caused by RDS were treated with NO in four concentrations [1, 5, 10, 20 parts per million (ppm) NO] and with placebo (0 ppm NO). Arterial blood gas measurements were drawn immediately before and at the end of each of the 15-minute treatments and were used to determine the arterial/alveolar oxygen ratio (PaO2/PAO2). Ten of the 11 infants had a greater than 25% increase in PaO2/PAO2. Five of the 11 had a greater than 50% increase in PaO2/PAO2. Despite normal cranial ultrasound imaging prior to NO, 3 infants had intracranial hemorrhage (ICH) noted on their first ultrasound scan after this brief period of NO treatment, and 4 additional infants developed ICH later during their hospitalization. No infant had significant elevations of methemoglobin concentrations after the total 60-minute exposure to NO. NO may be an effective method of improving oxygenation in infants with severe RDS. The disturbing incidence of ICH in this small group of infants needs to be carefully evaluated before considering routine use or NO for preterm infants.

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