Early prediction of a significant patent ductus arteriosus in infants <32 weeks gestational age.

BACKGROUND: The optimal thresholds for identification of preterm infants at greatest risk for adverse sequelae related to patent ductus arteriosus have not been well delineated. Our aim was to determine hemodynamic parameters in the first 24 hours using continuous non-invasive vital and structural measurements to predict which infants required PDA treatment in our institution. METHODS: Retrospective secondary analysis of data from infants born 23 to 32 weeks gestational age with cardiac output and stroke volume via electrical cardiometry, cerebral tissue oximetry measurements, mean arterial blood pressure (BP), heart rate, and oxygen saturation and functional echocardiography results at 12 hours of life were recorded when available (93 percent of subjects). RESULTS: A total of 292 infants, of which 55 (26±2 weeks, 862±268 grams) were treated for PDA. Treated infants demonstrated increased left ventricular output (p < 0.001) and lower mean BP (p = 0.010). The optimal area under the receiver operating characteristic curve (AUC) for predicting PDA treatment in our all gestations cohort is a mean BP at 15 hours of life of <33 mm Hg (AUC = 0.854, p < 0.001, 95% CI 0.792, 0.916). For infants <28 weeks a mean BP at 13 hours of life of <33 mm Hg (AUC = 0.741, p < 0.050, 95% CI 0.642, 0.839). CONCLUSIONS: In our cohort increased left ventricular output and lower mean BP predicted a clinically significant PDA requiring treatment.

Effects of delivery room quality improvement on premature infant outcomes.

OBJECTIVE: Delivery room management interventions have been successfully implemented via collaborative quality improvement (QI) projects. However, it is unknown whether these successes translate to reductions in neonatal morbidity and mortality. STUDY DESIGN: This was a prospective pre-post intervention study of three nonrandomized hospital groups within the California Perinatal Quality Care Collaborative. A collaborative QI model (Collaborative QI) was compared with a single-site QI model (NICU QI) and a non-participant population when implementing evidence-based delivery room practices. The intervention period was between June 2011 and May 2012. Infants born with gestational age between 22 weeks 0 days and 29 weeks 6 days and birth weight ⩽1500 g were included. Outcomes were mortality and select morbidities (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC)). Outcomes were compared between the baseline (January 2010 to May 2011) and post-intervention period (June 2012 to May 2013) within each comparison group. RESULTS: Ninety-five hospitals were included with 4222 infants in the baseline period and 4186 infants in the post-intervention period. The Collaborative QI group had significantly reduced odds of developing BPD post-intervention (odds ratio (OR) 0.8, 95% confidence interval (CI) 0.65 to 0.99) or composite BPD-death (OR 0.83, 95% CI 0.69 to 1.00). In both the Collaborative QI and non-participants there were also reductions in IVH, severe IVH, composite severe IVH-death, severe ROP and composite severe ROP-death. CONCLUSION: Hospitals dedicated to improving delivery room practices can impact neonatal outcomes.

The use of electrical cardiometry for continuous cardiac output monitoring in preterm neonates: a validation study.

BACKGROUND: Electrical cardiometry (EC) is a continuous noninvasive method for measuring cardiac output (CO), but there are limited data on premature infants. We evaluated the utility of EC monitoring by comparing the results obtained using EC to measurements of CO and systemic blood flow using echocardiography (ECHO). METHODS: In this prospective observational study, 40 preterm neonates underwent 108-paired EC and ECHO measurements. RESULTS: There were correlations between EC-CO and left ventricular output (LVO, p < 0.005) and right ventricular output (RVO, p < 0.005) but not with superior vena cava (r = 0.093, p = 0.177). Both RVO and LVO correlated with EC with and without a hemodynamically significant ductus arteriosus (p = 0.001 and 0.008, respectively). The level of agreement was decreased in infants ventilated by high-frequency oscillation ventilators (HFOV). The bias in HFOV was also positive compared with the negative biases found in other modes of ventilation. CONCLUSION: Given the correlation of EC with LVO, RVO, and lack of confounding effects of the ductus, our results suggest that EC has promise for trending CO in the preterm infant. However, given the limitations with mode of ventilation and the lack of correlation at low LVO values, further study is needed before this technology can be for routine use.

Impact of premedication on neonatal intubations by pediatric and neonatal trainees.

OBJECTIVE: To determine if premedication and training level affect the success rates of neonatal intubations. STUDY DESIGN: We retrospectively reviewed a hospital-approved neonatal intubation database from 2003 to 2010. Intubation success rate was defined as the number of successful intubations divided by the total number of attempts, and then compared by trainee's experience level and the use of premedication. Premedication regimen included anticholinergic, analgesic and muscle relaxant agents. RESULT: There were 169 trainees who completed 1071 successful intubations with 2694 attempts. The median success rate was 36% by all trainees, and improved with training level from 29% for pediatric trainees to 50% for neonatal trainees (P<0.001). Premedication was used in 58% of intubation attempts. The median success rate was double with premedication (43% versus 22%, P<0.001). CONCLUSION: Neonatal endotracheal intubation is a challenge for trainees. Intubation success rates progressively improve with experience. Premedication is associated with improved success rates for all training levels.

Evaluating retinopathy of prematurity screening guidelines for 24- to 27-week gestational age infants.

OBJECTIVE: To determine whether current retinopathy of prematurity (ROP) screening guidelines adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants. STUDY DESIGN: Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants of 24 (0)/7 to 27 (6)/7 weeks gestational age (GA) with consent before delivery were enrolled in 2005 to 2009. Severe ROP (type 1 ROP or treatment with laser, cryotherapy or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed the then current AAP (American Academy of Pediatrics) screening recommendations, beginning by 31 to 33 weeks postmenstrual age (PMA). RESULT: One thousand three hundred and sixteen infants were enrolled in the trial. Nine hundred and ninety-seven of the 1121 who survived to first eye exam had final ROP outcome determined. One hundred and thirty-seven (14% of 997) met criteria for severe ROP and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe ROP. PMA at onset was 32.1 to 53.1 weeks. In this referral center cohort, 1.4% (14/997) developed severe ROP after discharge. CONCLUSION: Our contemporary data support the 2013 AAP screening guidelines for ROP for infants of 24 (0)/7 to 27 (6)/7 weeks GA. Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide (iNO) has been proven to be effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Therefore, analysis of the efficacy and toxicities of iNO in infants born before 35 weeks is necessary. OBJECTIVES: To determine the effect of treatment with iNO on the rates of death, bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), or neurodevelopmental disability in preterm newborn infants (< 35 weeks gestation) with respiratory disease. SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) were searched, using the following keywords: nitric oxide, clinical trial, and newborn covering the years from 1985 to 2006. In addition, the abstracts of the Pediatric Academic Societies were also searched. SELECTION CRITERIA: Randomised and quasi-randomised studies in preterm infants with respiratory disease that compared the effects of administration of iNO gas compared to control, with or without placebo are included in this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including death, BPD (defined as oxygen dependence at 36 weeks postmenstrual age), IVH, periventricular leukomalacia (PVL), long term neurodevelopmental outcome and short term effects on oxygenation were excerpted from the trial reports by the investigators. Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Eleven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. The trials have been grouped post hoc into three categories depending on the entry criteria; entry in the first three days of life based on oxygenation criteria (Kinsella 1999; Hascoet 2004; INNOVO 2005; Van Meurs 2004; Mercier 1999; Dani 2006), routine use in intubated preterm babies (Schreiber 2003; Kinsella 2006) and later enrolment based on an increased risk of BPD (Subhedar 1997; Ballard 2006). The usefulness of the overall analyses was considered limited by the differing characteristics of the studies, and only subgroup analyses were performed. Trials of early rescue treatment of infants based on oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD. The subgroup of studies with routine use of iNO in intubated preterm infants demonstrated a marginally significant reduction in the combined outcome of death or BPD [typical RR 0.91 (95% CI 0.84, 0.99); typical RD -0.06 (95% CI -0.12, -0.01)]. Later treatment with iNO based on the risk of BPD demonstrated no significant benefit for this outcome in our analysis. Studies of early rescue treatment with iNO demonstrated a trend toward increased risk of severe IVH, whereas the subgroup of studies with routine use in intubated preterm infants seems to show a reduction in the risk of having either a severe IVH or PVL [typical RR 0.70 (95% CI 0.53, 0.91); typical RD -0.07 (95% CI -0.12, -0.02)]. Later iNO treatment of infants at risk of BPD is given after the major risk period for IVH, and does not appear to lead to progression of old lesions. Two studies (Schreiber 2003; INNOVO 2005) presented data on long term neurodevelopmental outcome. The early routine treatment study (Schreiber 2003) showed an improved outcome at two years corrected age, while the rescue treatment study (INNOVO 2005) showed no effect of iNO. AUTHORS' CONCLUSIONS: iNO as rescue therapy for the very ill ventilated preterm infant does not appear to be effective and may increase the risk of severe IVH. Later use of iNO to prevent BPD also does not appear to be effective. Early routine use of iNO in mildly sick preterm infants may decrease serious brain injury and may improve survival without BPD. Further studies are needed to confirm these findings, to define groups most likely to benefit, and to describe long term outcomes.

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn. OBJECTIVES: To determine whether treatment of hypoxaemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation (ECMO), or affects long term neurodevelopmental outcomes. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Trial reports were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes (particularly need for ECMO), and long term developmental outcomes were tabulated. STATISTICS: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis. MAIN RESULTS: Fourteen eligible randomized controlled studies were found in term and near term infants with hypoxia. Seven of the trials compared iNO to control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores. Four of the trials compared iNO to control, but allowed back up treatment with iNO if the infants continued to satisfy the same criteria for severity of illness after a defined period of time. Two trials enrolled infants with moderate severity of illness score (OI or AaDO2) and randomized to immediate iNO treatment or iNO treatment only if they deteriorated to more severe criteria. One trial studied only infants with congenital diaphragmatic hernia (Ninos 1997), and one trial enrolled both preterm and term infants (Mercier 1998), but reported the majority of the results separately for the two groups. Inhaled nitric oxide appears to improve outcome in hypoxaemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. Whether infants have clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) or not does not appear to affect outcome. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. The incidence of disability, incidence of deafness and infant development scores are all similar between tested survivors who received nitric oxide or not. AUTHORS' CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in an initial concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide compared to control with or without placebo. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular haemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study studied routine use of inhaled NO in all ventilated preterm infants (Schreiber 2003). The remaining studies consisted of infants with high predicted mortality based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs 2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect on the risk of intraventricular haemorrhage. There may be short term improvements in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented data on long term neurodevelopmental outcome, one of which demonstrated improved outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published evidence from randomised trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. Further studies may need to be performed to evaluate the potential benefit of routine use of this therapy in infants with milder forms of respiratory failure, and these trials will need to be designed to evaluate not only neonatal survival, and the occurrence of neonatal morbidities, but should be powered to evaluate neurodevelopmental outcome at a minimum of two years of age.

The sy-fi study: a randomized prospective trial of synchronized intermittent mandatory ventilation versus a high-frequency flow interrupter in infants less than 1000 g.

OBJECTIVE: Mechanical ventilation has significantly decreased mortality for preterm infants with respiratory distress syndrome. However, the barotrauma associated with mechanical ventilation is responsible for the development of bronchopulmonary dysplasia (BPD) in 20% to 90% of these infants, depending on gestational age. Recent studies suggest that high-frequency ventilation is associated with better gas exchange and less barotrauma. The purpose of this study is to determine if high-frequency ventilation, using the flow interrupter, reduces the incidence of BPD in the ELBW infant. STUDY DESIGN: Parental consent was obtained prior to mechanical ventilation. Infants less than 1000 g without significant congenital anomalies were eligible for study entry. Infants were randomized, prior to the onset of mechanical ventilation, to receive either synchronized intermittent mandatory ventilation (SIMV) or high-frequency flow interruption. Both ventilator methods were obtained using the Infant Star Ventilator (Mallinckrodt, St. Louis, MO). Data were collected prospectively on all study entrants and analyzed using SigmaStat Software. RESULTS: Forty-six infants, from two centers, were enrolled in this study. There was no significant difference in the ventilator days or BPD, defined as oxygen requirement at 36 weeks postmenstrual age, between the high-frequency ventilation and SIMV groups.

Sequential analysis for quality control in the neonatal intensive care unit.

OBJECTIVE: This article describes a novel application of a statistical technique for continuous quality assurance in the NICU. METHODS: We used prospective analysis of rates of survival to 28 days of life, without major IVH in ELBW infants in a single tertiary NICU, before and after the introduction of an evidence-based treatment protocol. By using the CUSUM function, each infant's results were sequentially plotted, and significant changes in outcomes were noted when the plot crossed predetermined boundary lines. RESULTS: Significant changes in outcomes were evident with this method sooner than traditional analyses on the basis of year-end or other arbitrary intervals. The introduction of the ELBW protocol was temporally associated with significant improvement in intact short-term survival. CONCLUSION: Sequential analysis techniques are useful tools for ongoing quality assurance; deviations in outcomes may be detected more quickly, which should assist in the identification of improvements or decrements in performance of the NICU.

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn. OBJECTIVES: To determine whether treatment of hypoxemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation (ECMO), or affects long term neurodevelopmental outcomes. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Trial reports were analyzed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes (particularly need for ECMO), and long term developmental outcomes were tabulated. STATISTICS: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis. MAIN RESULTS: Twelve eligible randomized controlled studies were found in term and near term infants with hypoxia. Entry criteria were reasonably consistent except for the one trial that studied only infants with congenital diaphragmatic hernia, and one trial that enrolled both preterm and term infants, but which reported the majority of the results separately for the two groups. Inhaled nitric oxide appears to improve outcome in hypoxemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. Whether infants have clear echocardiographic evidence of PPHN or not does not appear to affect outcome. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. The incidence of disability, incidence of deafness and infant development scores are all similar between tested survivors who received nitric oxide or not. REVIEWER'S CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in an initial concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (<35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular hemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2000. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomized and quasi randomized studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular hemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Three randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia. The second study consisted of infants with a 50% predicted mortality. The third study included term and preterm infants who had an oxygenation index of between 12.5 and 30, but randomised and analysed separately the preterm infants. No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. One study showed a reduction in days receiving assisted ventilation in the nitric oxide group, which was a secondary outcome. There was no evidence of effect on intraventricular hemorrhage incidence. There are no data on long term neurodevelopmental outcome. There may be short term improvements in oxygenation. REVIEWER'S CONCLUSIONS: The currently published evidence from randomized trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. There is a possible reduction in the severity of chronic lung disease (shortened duration of assisted ventilation). Because of lack of power, it is not possible to eliminate the possibility of substantial improvements in outcome. Further studies should be performed.

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (<35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular hemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2000. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomized and quasi randomized studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular hemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Three randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia. The second study consisted of infants with a 50% predicted mortality. The third study included term and preterm infants who had an oxygenation index of between 12.5 and 30, but randomised and analysed separately the preterm infants. No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. One study showed a reduction in days receiving assisted ventilation in the nitric oxide group, which was a secondary outcome. There was no evidence of effect on intraventricular hemorrhage incidence. There are no data on long term neurodevelopmental outcome. There may be short term improvements in oxygenation. REVIEWER'S CONCLUSIONS: The currently published evidence from randomized trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. There is a possible reduction in the severity of chronic lung disease (shortened duration of assisted ventilation). Because of lack of power, it is not possible to eliminate the possibility of substantial improvements in outcome. Further studies should be performed.

Comparison of methods of bag and mask ventilation for neonatal resuscitation.

BACKGROUND: There are a variety of manual bagging devices used for neonatal resuscitation. To our knowledge, there has been no comparison of the ability of different operators to utilize such devices for the delivery of predetermined inspiratory and end-expiratory pressures. In addition, the use of prolonged inflation may be of benefit for infants who require bag and mask ventilation, and there has been no evaluation of the ability of a variety of operators to reliably deliver such breaths using currently available equipment. METHODS: We utilized a neonatal manikin (Laerdal Armonk, NY) with a functional larynx and lungs, and a clear cushioned mask (Owens-BriGam, Morganton, NC). We studied a latex-free disposable anesthesia type bag (Model 5126 Vital Signs, Totawa, NJ), a Jackson-Rees (JR) type anesthesia bag (Model E191 Anesthesia Associates, San Marcos, CA) fitted with a Norman elbow and a flow-control tail-piece (Dupaco, Oceanside, CA), and the Neopuff (Fisher and Paykel, Auckland, New Zealand), an FDA approved mechanical device that is flow-controlled and pressure-limited, specifically designed to facilitate neonatal resuscitation. The ventilating pressures were continuously recorded throughout the process. We evaluated neonatal nurses, neonatal nurse practitioners, neonatal staff and fellows, pediatric residents and neonatal respiratory therapists. RESULTS: The peak inspiratory pressure (PIP) was significantly different between operators using either anesthesia bag, P<0.001. Similar results were found for positive end-expiratory pressure (PEEP) with a significant difference among the operator groups, P<0.001. All the differences in post hoc analysis were between the therapists and the other groups, P<0.05. Therapists produced significantly higher pressures than the other groups for both PIP and PEEP (P<0.001). The PIP was similar for all groups using the Neopuff device. The PIP and PEEP delivered by the Neopuff differed from the other two devices independent of the operators (P<0.05). On post hoc analysis, there was a significant difference between the disposable anesthesia bag and Neopuff for both PIP and PEEP for the therapists, whereas among the non-therapists, there was a difference in PIP with the JR device producing a greater PIP (26.6+/-3.8 cmH(2)O) compared with the Neopuff and disposable anesthesia bag (24.8+/-1.1 cmH(2)O, 24.8+/-4.3 cmH(2)O). The level of PEEP was significantly different among all three devices for the non-therapists (1.3+/-1.6 cmH(2)O, Disposable; 2.9+/-1.2 cmH(2)O, JR; 4.7+/-0.5 cmH(2)O, Neopuff; P<0.05). Only the therapists were able to consistently deliver PEEP with the anesthesia bags, whereas all operators could generate the target PEEP with the Neopuff (P<0.05). We compared the pressure delivered during the first second to the pressure delivered during the fifth second during prolonged 5-s inflations. The absolute differences between the first and fifth second for the Neopuff versus the anesthesia bags were significantly different with a median of 7.1 cmH(2)O for the anesthesia bags compared with 0.2 cmH(2)O for the Neopuff, P<0.001, reflecting the difficulty in obtaining and maintaining the target inflation pressures. CONCLUSIONS: Our experience suggests that the Neopuff, a purpose-built neonatal resuscitator ventilator, facilitates the delivery of the desired airway pressures while maximizing the operators ability to obtain and maintain a patent airway, and facilitates the delivery of prolonged inflations. Further research is required to determine the clinical benefit of end-expiratory pressure and prolonged inflations in neonatal resuscitation.

Randomized, prospective study of low-dose versus high-dose inhaled nitric oxide in the neonate with hypoxic respiratory failure.

OBJECTIVE: There is little information on the response to very low doses of inhaled nitric oxide (iNO) in hypoxic near-term infants. The potential toxicities of iNO are dose related; thus, the ability to use lower doses safely and effectively may be advantageous. We hypothesized that there is no difference in the acute improvement in oxygenation between treatment with inhaled nitric oxide at 1 to 2 parts per million (ppm) or 10 to 20 ppm. METHODS: We randomized near-term and term infants with hypoxic respiratory failure with oxygenation indices (OIs) of >/=10 and PaO(2) <100 on 2 separate blood gases taken at least 30 minutes apart. Infants with congenital diaphragmatic hernia were excluded. After parental consent was obtained, patients were randomized to receive a starting nitric oxide (iNO) dose of either 1 to 2 ppm (low-dose group, n = 15) or 10 to 20 ppm (high-dose group, n = 21). The response to iNO was assessed according to the increase in arterial PaO(2) and decrease in OI 30 to 60 minutes after exposure to the initial starting concentration. A response of <10% increase on PaO(2) and a <10% decrease in OI resulted in a doubling of iNO within the dose range protocol (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the high-dose group). RESULTS: Thirty minutes after the study gas was initiated, PaO(2) increased significantly overall in the low-dose (90.7 +/- 41 torr to 166.8 +/- 95.6 torr) and high-dose (76.2 +/- 32.7 torr to 198.7 +/- 142.8 torr) groups; the maximal increase was seen in the infants who initially were treated with 10 ppm. The OI also decreased significantly overall and also was significant in the high-dose group (21.0 +/- 13.7 to 11.4 +/- 10.4; low-dose: 18.3 +/- 7.1 to 13.2 +/- 12.3). There was a nonsignificant fall of PaCO(2) with iNO treatment (low dose 35 +/- 7.3 to 30 +/- 8.5 torr vs high dose 35.2 +/- 9.9 to 32.4 +/- 10.7 torr). A sustained response (ie, maintaining a PaO(2) and OI gain greater than 20% for the duration of the study gas administration) was greater in the high-dose group (53.3% vs 30.0%). In addition, dose increases were required more often in the low-dose group than in the high-dose group (80.0% vs 57.1%). Among patients who did not respond to the initial iNO dose, 100.0% and 83.3% responded at higher doses of iNO for the low- and high-dose groups, respectively. There were no differences for death, need for extracorporeal membrane oxygenation, or other outcomes between the groups. CONCLUSIONS: We did not find any significant difference in response to low- versus high-dose iNO. An initial exposure to low-dose iNO does not compromise the response to higher doses if required and may result in less toxicity.

Nitric oxide for respiratory failure in infants born at or near term.

BACKGROUND: Nitric oxide is a major endogenous regulator of vascular tone. Inhaled nitric oxide gas has been investigated as a treatment for persistent pulmonary hypertension of the newborn. OBJECTIVES: To determine whether treatment of hypoxemic term and near-term newborn infants with inhaled nitric oxide (iNO) improves oxygenation and reduces the rates of death, the requirement for extracorporeal membrane oxygenation (ECMO), or affects long term neurodevelopmental outcomes. SEARCH STRATEGY: Electronic and hand searching of pediatric/neonatal literature and personal data files. In addition we contacted the principal investigators of articles which have been published as abstracts to ascertain the necessary information. SELECTION CRITERIA: Randomized and quasi-randomized studies of inhaled nitric oxide in term and near term infants with hypoxic respiratory failure. Clinically relevant outcomes, including death, requirement for ECMO, and oxygenation. DATA COLLECTION AND ANALYSIS: Trial reports were analyzed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. Results of mortality, oxygenation, short term clinical outcomes (particularly need for ECMO), and long term developmental outcomes were tabulated. STATISTICS: For categorical outcomes, typical estimates for relative risk and risk difference were calculated. For continuous variables, typical estimates for weighted mean difference were calculated. 95% confidence intervals were used. A fixed effect model was assumed for meta-analysis. MAIN RESULTS: Eleven eligible randomized controlled studies were found in term and near term infants with hypoxia. Entry criteria were reasonably consistent except for the one trial that studied only infants with congenital diaphragmatic hernia (Ninos 1997), and one trial that enrolled both preterm and term infants (Mercier 1998), but which reported the majority of the results separately for the two groups. Inhaled nitric oxide appears to improve outcome in hypoxemic term and near term infants by reducing the incidence of the combined endpoint of death or need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced. Oxygenation improves in approximately 50% of infants receiving nitric oxide. The Oxygenation Index decreases by a (weighted) mean of 15.1 within 30 to 60 minutes after commencing therapy and PaO2 increases by a mean of 53 mmHg. Whether infants have clear echocardiographic evidence of PPHN or not does not appear to affect outcome. The outcome of infants with diaphragmatic hernia was not improved; indeed there is a suggestion that outcome was slightly worsened. The incidence of disability, incidence of deafness and infant development scores are all similar between tested survivors who received nitric oxide or not. REVIEWER'S CONCLUSIONS: On the evidence presently available, it appears reasonable to use inhaled nitric oxide in an initial concentration of 20 ppm for term and near term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.

Randomized trial of nasal synchronized intermittent mandatory ventilation compared with continuous positive airway pressure after extubation of very low birth weight infants.

OBJECTIVE: To determine whether noninvasive, nasal synchronized intermittent mandatory ventilation (nSIMV) improves the likelihood that very low birth weight infants will be successfully extubated. METHODS: Infants of <1251-g birth weight who were due to be extubated before 6 weeks of age were eligible once they were receiving <35% oxygen and were on a ventilator rate of <18 breaths per minute (bpm). Extubation was performed following intravenous loading with aminophylline, after a successful trial of 12 hours of endotracheal synchronized intermittent mandatory ventilation at a rate of 8. Infants were randomized to either nasal continuous positive airway pressure (nCPAP) at 6 cm H(2)O or nSIMV after extubation. nSIMV was commenced at a rate of 12 bpm with pressure on the ventilator set to achieve a delivered pressure of at least 12 cm H(2)O and a peak end expiratory pressure of 6 cm H(2)O. Continuous recording for diagnosis of apnea was performed for 72 hours after extubation. Objective criteria for failure of extubation were as follows: a PaCO(2) >70; FIO(2) >0.7; or severe recurrent apnea (>2 apneas requiring intermittent positive-pressure ventilation in 24 hours or >6 apneas >20 seconds per day). The study ended after 72 hours postextubation or when infants satisfied failure criteria. A sample size of 54 was determined by power analysis. RESULTS: Mean birth weight (831 standard deviation [SD]: 193 g) and gestation (26.3 SD: 1.8 weeks) did not differ between groups. Mean age at extubation was 7.6 (SD: 9.7) days, range 1 to 40 days. The nSIMV group had a lower incidence of failed extubation 4/27 compared with the continuous positive airway pressure group, 12/27. This was attributable to both a decreased incidence of apnea and a decreased incidence of hypercarbia. There was no increase in the incidence of abdominal distension or feeding intolerance. DISCUSSION: nSIMV is effective in preventing extubation failure in very low birth weight infants in the first 72 hours after extubation. Noninvasive ventilation may have other roles in the care of the very low birth weight infant.

Video recording as a means of evaluating neonatal resuscitation performance.

OBJECTIVE: To determine the compliance to Neonatal Resuscitation Program (NRP) guidelines in our institution, by the use of videotaped newborn resuscitations. BACKGROUND: NRP is the standard of care for newborn resuscitation. The application of NRP guidelines and resuscitation skills in actual clinical settings is undocumented. DESIGN/METHODS: A video recorder, mounted to the radiant warmer in the main obstetrical operating room, was used to record all high-risk resuscitations. All members of the resuscitation team were NRP-certified. The videotapes were reviewed within 14 days of the resuscitation and then erased. This ongoing review was approved as a quality assurance (QA) project ensuring confidentiality under California law. The first 100 resuscitations were evaluated to assess NRP compliance. Each step in the resuscitation (positioning, oxygen delivery, ventilation, chest compressions, intubation, and medication) was graded. A score was devised, with 2 points being awarded for every correct decision and proper procedure, 1 point for delayed interventions or inadequate technique, and zero points for indicated procedures that were omitted or for interventions that were not indicated. The total points were divided by the total possible points for that patient. The scores for the first 25 resuscitations (group 1) and the last 25 resuscitations (group 2) were compared. RESULTS: Fifty-four percent of the 100 resuscitations had deviations from the NRP guidelines. Ten percent received overly aggressive stimulation and 22% had poor suction technique. Of the 78 infants given oxygen, this decision was considered incorrect in 15% and the delivery technique was poor in 10% of the infants given oxygen. Of those requiring mask ventilation (n = 18), 24% had poor chest expansion, 11% used an incorrect rate, and 17% had inadequate reevaluation. Twelve infants were intubated; only 7 were successfully intubated on the first attempt and only 4 were intubated in <20 seconds. The longest intubation attempt was 50 seconds. Naloxone was given to 2 patients. One was breathing spontaneously with a heart rate >100. Resuscitations receiving a perfect evaluation score were more likely to occur in infants needing less intervention. The level of resuscitation required for groups 1 and 2 were statistically similar. There was no difference in resuscitation scores between the 2 groups. Only the inappropriate use of deep suctioning improved, with 8 of 25 events in group 1, and 0 of 25 in group 2. CONCLUSIONS: We have found a significant number of deviations from the NRP guidelines. Video recording of actual clinical practice is a useful QA tool for monitoring the conduct of newborn resuscitation. We are now conducting repeat video assessments of individual NRP providers to determine whether there is improved performance.

Effects of magnesium sulfate in a newborn piglet meconium aspiration model.

OBJECTIVE: To examine the hemodynamic effects of magnesium sulfate (MgSO4) in a neonatal model of meconium aspiration syndrome. DESIGN: A prospective animal study. PATIENTS AND PARTICIPANTS: Eight anesthetized neonatal piglets. METHODS: Animals were instrumented under fentanyl anesthesia for the determination of pulmonary and systemic blood pressures and cardiac index. A model of meconium aspiration was produced by instilling 6 to 7 ml of 20% fresh human meconium in normal saline down the endotracheal tube, resulting in hypoxemia (mean arterial O2 saturation 73 SD, 10%), respiratory acidosis (mean pH 7.08, SD 0.04; PaCO2 89, SD 2 torr), and pulmonary arterial hypertension (mean pulmonary artery pressure 52 SD, 5 mm Hg). A total of four aliquots of MgSO4 (25 mg/kg equivalent to 0.1 mM/kg of magnesium) were administered intravenously to five animals (total of 100 mg/kg MgSO4). Three animals served as controls and did not receive MgSO4. RESULTS: Each dose of MgSO4 was associated with a transient decrease in heart rate, cardiac index, pulmonary and systemic arterial pressures, and SaO2, followed by a partial gradual recovery of all these variables within 2 to 3 minutes. According to measurements taken after MgSO4 therapy, there was a significant decrease in arterial saturations (from 73 SD (10%) to 63 SD (13%); p < 0.05), mean systemic blood pressure (from 77 SD (16 mm Hg) to 74 SD (15 mm Hg); p < 0.05) and pulmonary artery pressure (to 52 SD (5 mm Hg); p < 0.05). The ratio between pulmonary and systemic vascular resistance was not significantly affected by MgSO4 therapy. There were no changes in the control animals. CONCLUSION: The administration of magnesium sulfate is associated with increased hypoxemia in this model of meconium aspiration syndrome, probably because of worsening ventilation perfusion mismatch. These data do not provide any physiological support for the use of MgSO4 in the neonate with meconium aspiration and pulmonary hypertension and suggest that this agent should be used cautiously, if at all, in such situations.