Development of a statewide collaborative to decrease NICU central line-associated bloodstream infections.

OBJECTIVE: To characterize hospital-acquired bloodstream infection rates among New York State's 19 regional referral NICUs (at regional perinatal centers; RPCs) and develop strategies to promote best practices to reduce central line-associated bloodstream infections (CLABSIs). STUDY DESIGN: During 2006 and 2007, RPC NICUs reported bloodstream infections, patient-days and central line-days to the Department of Health, and shared their results. Aiming to improve, participants created a central line-care bundle based on visiting a potentially best performing NICU and reviewing the literature. RESULT: All 19 RPCs participated in this quality initiative, contributing 218,096 patient-days and 56,911 central line-days of observation. Individual RPC nosocomial sepsis infection (NI) rates ranged from 1.0 to 5.8 NIs per 1000 patient-days (2006), and CLABSI rates ranged from 2.6 to 15.1 CLABSIs per 1000 central line-days (2007). A six-fold rate variation among RPC NICUs was observed. Participants unanimously approved a level-1 evidence-based central line-care bundle. CONCLUSION: Individual RPC rates and consequent morbidity and resource use attributable to these infections were substantial and varied greatly. No center was without infections. It is hoped that the cooperation and accountability exhibited by the RPCs will result in a major network for characterizing performance and improving outcomes.

Environmental exposures and respiratory morbidity among very low birth weight infants at 1 year of life.

INTRODUCTION: Preterm infants have a substantially increased risk of developing respiratory illnesses. The goal of this study was to consider the impact of modifiable postnatal exposures on respiratory morbidity among a cohort of very low birth weight (VLBW) infants. OBJECTIVES: (1) Assess the rates of respiratory morbidity and exposure to indoor respiratory triggers in a population of VLBW infants at 1 year; (2) determine the association between exposures and respiratory morbidity. METHODS: We enrolled 124 VLBW infants into a prospective cohort study. Parents were called at 1 year to assess respiratory outcomes and environmental exposures. We used bivariate and multivariate analyses to assess the relationship between environmental exposures and acute care for respiratory illnesses. RESULTS: At 1 year, 9% of infants had physician-diagnosed asthma, 47% required >or=1 acute visit and 11% required hospitalisation for respiratory illness. The majority of infants (82%) were exposed to at least one indoor respiratory trigger. Infants living with a smoker (61% vs 40%) and infants exposed to pests (62% vs 39%) were more likely than unexposed infants to require acute care for respiratory problems. In a multivariate regression controlling for demographics, birth weight, bronchopulmonary dysplasia, and family history of asthma or allergies, both living with a smoker (OR 2.62; CI 1.09 to 6.29) and exposure to pests (OR 4.41; CI 1.22 to 15.94) were independently associated with the need for acute care for respiratory illnesses. CONCLUSIONS: In this sample, respiratory morbidity and exposure to triggers were common. VLBW infants may benefit from interventions that decrease exposure to respiratory triggers.

Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

BACKGROUND: Both prophylactic and early surfactant replacement therapy reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS) compared with later selective surfactant administration. However, continued post-surfactant intubation and ventilation are risk factors for bronchopulmonary dysplasia (BPD). The purpose of this review was to compare outcomes between two strategies of surfactant administration in infants with RDS; prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation. OBJECTIVES: To compare two treatment strategies in preterm infants with or at risk for RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation vs. later selective surfactant administration, continued mechanical ventilation, and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (who receive surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (who receive prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2006), CINAHL (1982 to December Week 2, 2006), EMBASE (1980 - December 2006), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006), Pediatric Research (1990 - 2006), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation vs. selective surfactant administration continued mechanical ventilation, and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on the incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, duration of oxygen therapy, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Stratified analysis was performed according to inspired oxygen threshold for early intubation and surfactant administration in the treatment group: inspired oxygen within lower (FiO2< 0.45) or higher (FiO2 > 0.45) range at study entry. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. MAIN RESULTS: Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2< 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13]. AUTHORS' CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2< 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2< 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

BACKGROUND: Both prophylactic and early surfactant replacement therapy, compared with later selective surfactant administration, reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). However, continued post-surfactant intubation and ventilation are risk factors for chronic lung disease. Whether prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation reduces the need for mechanical ventilation and the incidence of chronic lung disease is unknown. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2003), CINAHL (1982-December 2003), EMBASE (1980-December 2003), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), Pediatric Research (1990-2003), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. MAIN RESULTS: Four randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.70, 95% CI 0.59, 0.84]. None of the trials reported a significant difference in the incidence of BPD or CLD; however, meta-analysis for this outcome cannot yet be performed because the primary data from three of the trials have not yet been published in full. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.59, 95% CI 1.35, 1.88]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.51 doses per patient, 95% CI 0.36, 0.65]. Trends towards a decreased incidence of air leak syndromes (two studies) and a higher incidence of patent ductus arteriosus requiring treatment (one study) were seen in the early surfactant group. There was no evidence of effect on time in oxygen or duration of mechanical ventilation. REVIEWERS' CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. There is insufficient evidence at present to reliably evaluate effect on BPD or CLD.

Early surfactant administration with brief ventilation vs selective surfactant and continued mechanical ventilation for preterm infants with or at risk for RDS.

BACKGROUND: Both early and prophylactic surfactant replacement therapy compared with later selective surfactant administration reduces mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS). Continuous distending pressure (CDP) has also been shown to improve clinical outcomes in preterm infants with RDS. OBJECTIVES: To compare two treatment strategies in preterm infants with, or at risk for, RDS: early surfactant administration with brief mechanical ventilation (less than 1 hour) followed by extubation, vs later, selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (prophylactic surfactant administration within 15 minutes after birth). SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal trials, MEDLINE (1966-December 2001), CINAHL (1982-December 2001), EMBASE (1980-December 2001), Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), Pediatric Research (1990-2001), abstracts, expert informants and hand searching. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation, vs selective surfactant administration, continued mechanical ventilation and extubation from low respiratory support. DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD, need for oxygen at 28 days of age), incidence of chronic lung disease (CLD, need for oxygen at 36 weeks' post-conceptional age), mortality (neonatal mortality < 28 days and mortality prior to hospital discharge), duration of mechanical ventilation, duration of hospitalization, time in oxygen, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), incidence of pulmonary hemorrhage, and other complications of prematurity. Data analyses were performed in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Only one randomized controlled clinical trial met selection criteria and was included in this review (Verder 1994). In this study of infants with signs of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later, selective surfactant administration was associated with a lower incidence of mechanical ventilation (ventilation continuing for one hour or more after surfactant administration in the early surfactant group or initiated for respiratory insufficiency or apnea in either group [RR 0.51, 95% CI 0.32, 0.76]). A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [RR 1.74, 95% CI 1.30, 2.33]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [MD 0.51, 95% CI 0.32, 0.70]. Trends towards a decreased incidence of mortality, and a higher rate of patent ductus arteriosus requiring treatment were seen in the early surfactant group. There was no evidence of effect on median time in oxygen, duration of mechanical ventilation, or incidence of BPD (oxygen at 28 days). REVIEWER'S CONCLUSIONS: Early surfactant replacement therapy with extubation to NCPAP compared with later, selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with a reduced need for mechanical ventilation and increased utilization of exogenous surfactant therapy. These conclusions are based on findings from one small randomized clinical trial. Additional randomized trials are needed and are underway.

Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis.

OBJECTIVES: To assess the risk of hospitalization associated with respiratory syncytial virus (RSV) and to estimate the economic impact of RSV prophylaxis with either RSV immune globulin (RSV-Ig) or RSV monoclonal antibody (palivizumab) on a cohort of preterm infants born at 32 weeks' gestation or earlier. DESIGN: Historical cohort study. SETTING: A 12-county neonatal network served by the regional center in Rochester, NY. PARTICIPANTS: One thousand twenty-nine infants born at 32 weeks' gestation or earlier followed up until 1 year of corrected age. MAIN OUTCOME MEASURES: Rate of hospitalization with an RSV-associated illness; cost per hospitalization prevented resulting from either form of RSV prophylaxis. RESULTS: The probability of hospitalization with an RSV-associated illness for infants born at 32 weeks' gestation or earlier was estimated at 11.2%. The incidence of RSV hospitalization increased with decreasing gestational age (13.9% vs 4.4% for infants born at < or =26 weeks' gestation vs those born at 30-32 weeks' gestation). Infants requiring respiratory support at 36 weeks of postconceptual age (PCA) or older had a higher hospitalization rate (16.8% vs 6.2%), longer hospital stays, and higher hospital charges than infants requiring respiratory support at less than 36 weeks of PCA. For infants requiring respiratory support at less than 36 weeks of PCA, the incidence of RSV hospitalization still increased with decreasing gestational age (10.2% vs 4.3% for infants < or =26 weeks' gestation vs those 30-32 weeks' gestation). Analysis indicated that both forms of RSV prophylaxis would increase the net cost of care for all groups. Palivizumab was more cost-effective than RSV-Ig for preventing RSV hospitalization among infants who required respiratory support at less than 36 weeks of PCA, especially those born at 26 weeks' gestation or earlier. Overall, RSV-Ig was more cost-effective than palivizumab for infants requiring respiratory support at 36 weeks of PCA or older. CONCLUSIONS: This analysis suggests that available forms of RSV prophylaxis would increase the net cost of care not only for the entire cohort but for each of the subgroups studied. However, the RSV hospitalization rate and the cost-effectiveness of prophylaxis varied markedly by subgroup.

Cell proliferation contributes to PNEC hyperplasia after acute airway injury.

Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells that are capable of secreting a variety of neuropeptides. PNECs are scattered throughout the bronchial tree either as individual cells or clusters of cells termed neuroepithelial bodies (NEBs). PNECs and their secretory peptides have been considered to play a role in fetal lung development. Although the normal physiological function of PNECs and neuropeptides in normal adult lungs and in repair from lung injury is not known, PNEC hyperplasia has been associated with chronic lung diseases, such as bronchopulmonary dysplasia, and with chronic exposures, such as hypoxia, tobacco smoke, nitrosamines, and ozone. To evaluate changes in PNEC number and distribution after acute airway injury, FVB/n mice were treated with either naphthalene or vehicle. Naphthalene is an aromatic hydrocarbon that, at the dose used in this study, selectively destroys nonciliated bronchial epithelial cells (Clara cells) through cytochrome P-450-mediated metabolic activation into cytotoxic epoxides. PNECs were identified by immunohistochemical analysis of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Proliferating cells were marked with [(3)H]thymidine incorporation. Acute naphthalene toxicity results in PNEC hyperplasia that is detectable after 5 days of recovery. PNEC hyperplasia is characterized by increased numbers of NEBs without significant changes in the number of isolated PNECs and by increased [(3)H]thymidine labeling of CGRP-IR cells. These data show that cell proliferation contributes to PNEC hyperplasia after acute airway injury and suggest that PNECs may be capable of more rapidly increasing their number in response to injury than previously recognized.

Use of glucagon to treat neonatal low-output congestive heart failure after maternal labetalol therapy.

Labetalol is used to treat hypertensive crisis in women with preeclampsia. Glucagon was used as a nonselective beta-adrenergic agonist to treat a preterm infant with symptomatic beta-blockade caused by maternal labetalol therapy.