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BACKGROUND Early Onset Sepsis (EOS) is associated with increased major morbidity and mortality rates among very low birth weight (VLBW) infants. The epidemiology is changing in response to evolving medical practice. The objective of the study was to evaluate EOS epidemiology, risk factors, mortality and major morbidity rates among VLBW infants within a European cohort. METHODS Data from VLBW infants born from 2006 through 2009 was collected by neonatal units participating in the EuroNeoNet initiative. Univariate and multivariate analyses were performed to assess the independent association of EOS with VLBW infant's perinatal characteristics, morbidity and mortality rates. RESULTS The cohort included 14,719 infants, 391 developed EOS (2.7%). The most common pathogen responsible for EOS was Gram-positive bacteria (53.9%). Coagulase-negative staphylococci (CoNS) were isolated in 22.5% of episodes. Antenatal steroids exposure, single gestation, very low gestational age and birth weight, low 5 minute Apgar score and delivery room resuscitation were independently associated with EOS. EOS was also associated with a longer hospital stay, increased risk of mortality [adjusted odd ratio (aOR): 2.4; 95% Confidence Interval (CI): 1.9-3.1], respiratory distress syndrome (OR: 1.4; 95% CI: 1.1-1.9), severe intraventricular haemorrhage (aOR: 2.1; 95%CI: 1.6-2.8) and severe retinopathy of prematurity (aOR: 5; 95% CI: 1.9-13.3). Morbidity and mortality rates of infants with EOS caused by CoNS were similar to those of infants with EOS caused by other pathogens. CONCLUSIONS VLBW infants with EOS are at an increased risk of mortality and major morbidities. CoNS was a significant cause of sepsis, infants with CoNS were at a similarly high risk of complication of prematurity and mortality as those with EOS caused by other organisms.

Surfactant (SF) instillation may produce acute deleterious effects on gas exchange and both systemic and cerebral hemodynamics. Our aim was to compare the effects of aerosolized SF (SF-aero) with those of bolus SF (SF-bolus) administration on gas exchange, lung mechanics, and cardiovascular function in premature lambs with respiratory distress syndrome (RDS).Fourteen preterm lambs (85% gestation) were randomly assigned to receive SF-aero or SF-bolus. Oxygenation index (OI), PaCO2, cardiovascular parameters, carotid blood flow (CBF), lung compliance (mean dynamic compliance), and tidal volume (VT) were measured every 30 min for 6 h. Biochemical and histological analyses were performed.After delivery, lambs developed severe RDS (inspiratory fraction of oxygen: 1; pH7.15; PaCO280 mm Hg; PaO230 mm Hg, mean dynamic compliance0.08 ml/cm H2O/kg). By 60 min after treatment, both groups showed an improvement in OI, PaCO2, mean dynamic compliance, and VT that was maintained until the end of the experiment. PaCO2 and CBF increased significantly in the SF-bolus group during the first 15-30 min, without concomitant changes in cardiovascular parameters, whereas in the SF-aero group, PaCO2 and CBF decreased gradually. SF-aero induced less alveolar hemorrhage and inflammation.SF-aero produced improvements in gas exchange and lung mechanics similar to those produced by bolus administration but with less lung injury and fewer cerebral hemodynamic changes.

Background: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans.\ud \ud Methods: Newborn pigs (n=18) were exposed to 2h-hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4h). After 1h-reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15μg/kg/min or 15-20μg/kg/min. Dobutamine groups received two dobutamine doses during 30min with a 60min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF.\ud \ud Results: Hypoxia significantly decreased CI, systemic-vascular-resistance and mean-arterial-bloodpressure (MABP). Dobutamine doses significantly increased heart-rate, CI and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15μg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared-spectroscopy. A positive correlation was observed between SVCF and CI.\ud \ud Conclusion: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific\ud differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.

OBJECTIVE Today, in meconium aspiration syndrome, treatment focuses on bronchoalveolar lavage, because it removes meconium and proinflammatory factors from airways. This technique might be more effective if different solutions were used such as saline solution, a protein-free surfactant, or a perfluorocarbon, because these would be less inhibited by meconium proteins. SETTING Pulmonary physiology research unit, Cruces Hospital. DESIGN Prospective, randomized study. SUBJECTS We studied 24 lambs (

This study was designed to study effects of lung lavage versus the classical bolus instillation with a peptide-based synthetic surfactant (lucinactant) in a model of Meconium Aspiration Syndrome (MAS). Eighteen newborn lambs received meconium and were randomized to: the experimental meconium installation (eMAS) group—lambs with eMAS kept on conventional mechanical ventilation (control); the SF-Bolus group—eMAS receiving a lucinactant bolus (30 mg/ml); or the D-SF-Lavage group—eMAS treated with dilute lucinactant bronchoalveolar lavage (10 mg/ml). Systemic and pulmonary arterial pressures, blood gases, and pulmonary mechanics were recorded for 180 min. In addition, the intrapulmonary distribution of the lucinactant was determined using dye-labeled microspheres. Following meconium instillation, severe hypoxia, hypercapnia, acidosis, and pulmonary hypertension developed, and dynamic compliance decreased (50% from baseline). After lung lavage with dilute lucinactant, gas exchange significantly improved versus bolus instillation (P

The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds.The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds.With IC-1.23 significantly higher aerosol production rates were achieved (p 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 μm (PFD) and 8.29 μm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 μm (FC75) and 13.42 μm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems.Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.

Aim: To review respiratory syncytial virus (RSV), passive immunoprophylaxis (PI) trials and meta-analysis (MA). Methods: A literature review. Results: Two MA of PI were found. Overall 3927 patients were randomized. PI reduces RSV hospitalization in patients with bronchopulmonary dysplasia (RR 0.58; 95% CI 0.41, 0.82) and with acyanotic congenital heart disease (RR 0.29; 95% CI 0.14, 0.62). In patients with cyanotic heart disease or premature infants without bronchopulmonary dysplasia, results are inconclusive. Passive immunoprophylaxis has a null effect in mechanical ventilation and death. Conclusion: Passive immunoprophylaxis reduces RSV hospitalization in a subset of patients. However, it has no effect in harder endpoints of RSV disease severity.

Hospital-acquired infections cause significant mortality and morbidity in preterm infants and increase the length of stay and costs. Differences in the quality of care may be at least partially responsible for the substantial variability seen in the incidence of such infections among different institutions. Various quality assurance programs within neonatal networks around the world target these infections, aiming to reduce their incidence. Comprehensive surveillance programs seem to be effective, especially if educational activities are added on local and network levels, and may help to save lives.

Resumen: Objetivo: conocer el tipo de unidades de cuidados intensivos neonatales (UCIN) que proporcionan asistencia respiratoria neonatal en España y sus características. Material y método: encuesta multicéntrica estructurada para conocer la actividad asistencial respiratoria prestada por las UCIN en 2005. Resultados: contestaron 96 unidades neonatales con una representatividad estimada en un 63%, con un intervalo entre el 3 y el 92%, según las áreas geográficas; las unidades IIIc se encuentran en el rango superior. Contestaron la encuesta 26 unidades tipo IIb (27%), 16 IIIa (17%), 40 IIIb (42%) y 14 IIIc (14%). Las camas totales de intensivos de nivel III fue de 541 (1,2 camas cada 1.000 recién nacidos vivos; intervalo, 0,7-1,7). La media de camas por unidad fue de 4,1 para las IIIa, 2,8 para las IIIb y 14,6 para las IIIc. En las unidades de nivel III, la relación camas/médicos fue de 2,4 camas/medico y la de camas/enfermeras 2,8 camas/enfermera (2,2 en nivel IIIc). Hubo un total de 13.219 ingresos, de los que el 54% precisó ventilación (el 36% en las IIIa y el 65% en las IIIc). La posibilidad de reanimación en el paritorio con mezcla de gases (aire y oxígeno) sólo la tiene el 42% de las IIIb y IIIc. La relación respirador/cama fue de 1/1; el 63% puede proporcionar ventilación de alta frecuencia (VAF). Todas disponen de sistemas de presión positiva continua nasal (CPAP-n). Sistemas para aplicar ventilación nasal intermitente están disponibles en el 25% de las IIIa, el 58% de las IIIb y el 64% de las IIIc. Todas las IIIc y el 93% de las IIIb pueden proporcionar oxido nítrico inhalado. Cuatro unidades disponían de ECMO. Conclusiones: la media de camas de UCIN de nivel III cada mil nacidos está en el límite bajo de lo recomendable, con notables diferencias regionales. La necesidad de ventilación mecánica fue del 54%. La relación de camas por enfermera fue de 2,8. Existe una buena dotación de respiradores (1 por cama) con alta disponibilidad de VAF (63%). Todas las unidades disponen de CPAP-n. Abstract: Aim: To learn the characteristic of the neonatal intensive care units (NICUs) that offer neonatal respiratory assistance in Spain. Material and method: A structured survey was developed and sent to all Spanish neonatal units to learn about the respiratory care offered in 2005. Results: A total of 96 Units answered the survey, with an estimated representatively of 63%, with a range from 3 to 92%, depending on the geographical area. Level IIIc Units were in the upper range. Answer the survey 26 units type IIb (27%), 16 IIIa (17%), 40 IIIb (42%) and 14 IIIc (14%). The total number of level III NICU beds was 541 (1.2 beds per 1000 livebirths; range, 0.7–1.7). The mean number of beds per NICU was 4.1 in level IIIa Units, 2.8 in those IIIb and 14.6 in type IIIc NICUs. In level III NICUs, the bed per physician ratio was 2.4 and that of beds per registered nurse was 2.8 (2.2 in level IIIc NICUs). There were a total 13,219 admissions, 54% of those needed mechanical ventilation (36% in IIIa and 65% in level IIIc NICUs). Oxygen blenders for resuscitation at birth were available in 42% of level IIIb and IIIc NICUs. NICUs had one neonatal ventilator per bed, and 63% of units had high frequency ventilation available. All units had nasal-CPAP systems, 25% of level IIIa Units, 58% IIIb and 64% of those type IIIc had systems for nasal ventilation. All level IIIc and 93% of level IIIb NICUs were able to provide inhaled nitric oxygen therapy. Four NICUS offered ECMO. Conclusions: The mean number of NICU beds per 1000 livebirths is within the lower limits of those been recommended, and there were wide variations among different geographical areas. A 54% of those babies admitted to NICUs required mechanical ventilation. The mean number of NICU beds per registered nurse was 2.8. There was an adequate number of neonatal ventilators (one per bed) and 63% were able to provide HFV. All NICUs hand n-CPAP systems.

Aim: To study if medication error rate decreased as a consequence of a simple observation process of registering its occurrence. Methods: Prescription and transcription processes were prospectively registered along two different period of time in a level III regional Neonatal Intensive Care Unit: a pilot phase, aimed to know the baseline drug error rate and a phase I, a pre-intervention phase, both part of a study designed to determinate the effect of a preventive strategy in drug error rate. Random drug prescriptions by physicians and their transcriptions by nurses were reviewed and registered by a hospital pharmacist. A drug error episode was registered if dosage, units, route and administration interval were incorrect, illegible or not indicated. Results: A significant reduction in the prescription error rate from 32.8% in the pilot phase to 19.2% in the pre-intervention study phase was observed (p< 0.001). Rates of incorrect dosing (13.6% vs. 5%) and lack of dose specification in the medical prescriptions (3.3% vs. 0.5%) dropped significantly but transcription errors did not. Conclusion: The presence of a person reviewing and registering the drug records apparently had by itself a substantial positive effect on the overall drug error rate. This phenomenon known as the Hawthorne effect should be taken in consideration when evaluating the efficacy of any preventive intervention aimed at improving patient safety.

An online postgraduate training programme for doctors training to be specialists in neonatology was developed and delivered over one year within a virtual learning environment. Ninety trainee doctors from 14 European countries participated, the majority of whom had expressed a need for increased theoretical knowledge. Fourteen clinicians supported the cross-cultural learning groups as online tutors following specific online training. Analysis of logins and postings showed a wide variation in online activity for both tutors and trainees. The online activity of tutors appeared to influence learner activity. Initially participation was very good but during the year there was a steady decline such that by the end of the programme only 46% of the trainees and 71% of tutors were actively participating. Despite this, a large majority (92%) of the 67 trainees who provided end-of-programme evaluation data reported that participation had “added value” to their training and 84% felt the programme had achieved its aims and objectives. All of the tutors and 90% of trainees would choose to participate again; the main limiting factor for both groups was a lack of time. Our findings suggest that future online programmes should ensure that “protected” time is provided for both trainees and tutors and that there should be formal integration with existing training programmes and accreditation processes.

Teamwork is an important aspect of all fields of human knowledge, including health-related activities. Networking is a form of cooperation that can enhance the efficiency and effectiveness of any project by collaboration toward common goals. New Internet-based information and communication technologies increase opportunities for collaboration among scientists and clinicians. In the medical field, networking has been used to improve the quality of health care by disseminating information on evidence-based effective and ineffective or dangerous interventions (eg, through the Cochrane Collaboration) and promoting high-quality clinical research. Neonatal networking can be defined as collaborative work involving several neonatal intensive care units (NICUs) sharing a common protocol aimed to collect standardized patient data for external audits (benchmarking), clinical trials, and quality of care improvement projects. The first example of successful neonatal networking appeared in 1953, when the National Institutes of Health sponsored a clinical trial of the restriction of supplemental oxygen delivery to very low-birthweight (VLBW) infants. It was performed in 18 NICUs and resulted in a sharp decline in the incidence of retinopathy of prematurity leading to blindness. (1) Since then, a large number of sufficiently sized, well-designed, randomized clinical trials have been conducted and published, exerting a strong impact on neonatal care throughout the world. (2) Other neonatal networks have been established as stable, ongoing organizations that have wider missions, not only to perform high-quality clinical research but to promote excellence in clinical practice by the use of standardized comparisons of outcomes, teaching and training of health personnel involved in neonatal care, and setting of high standards for the care of preterm infants. Such networks are supported by public funds (eg, the National Institute of Child Health and Human Development [NICHD] Neonatal Network (3) and the Australian and New Zealand Neonatal Network \[ANZNN\] (4)), membership fees (eg, the Vermont-Oxford Network …

Aim: To evaluate the effect of cerebral hypoxia-ischaemia induced by partial occlusion of the umbilical cord on the relationship of the regional cerebral blood flow and the cerebral cell death in near-term fetal lambs. Methods: Fifteen near-term lambs were assigned to two hypoxic-ischaemic groups with or without life support (3 h), and a healthy one. Hypoxia-ischaemia was induced by partial occlusion of the umbilical cord (60 min). Routine light and electron microscopy, and the TUNEL method for apoptosis were performed. Regional cerebral blood flow was measured by coloured microspheres. Cardiovascular, gas exchange and pH parameters were also evaluated. Results: Both hypoxic-ischaemic groups produced a transient acidosis and a decrease of base excess in comparison to the healthy group. Cortical and cerebellar zones, where the regional cerebral blood flow values were similar to baseline, showed an increased number of oligodendrocyte-like apoptotic cells. In contrast, in the inner zones, where regional cerebral blood flow was increased, the number of apoptotic cells did not increase. Necrotic neurons were observed in the basal nuclei, mesencephalon, pons and deep cerebellar nuclei. Conclusion: Our results suggest that regional cerebral blood flow and the presence of apoptotic cells, 3 h after hypoxic-ischemic injury, are correlated.

Objective Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome. Design Prospective randomized study. Setting BioCruces Institute Animal Research Facility. Subjects Fourteen intensively monitored and mechanically ventilated preterm lambs. Interventions Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis. Measurements and main results In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress. Conclusions In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of surfactant administered as a standard bolus.