Cardiac Depression in Pigs after Multiple Trauma - Characterization of Posttraumatic Structural and Functional Alterations.

The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1ß generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.

Risk Factors Associated with Intraventricular Hemorrhage in Preterm Infants with ≤28 Weeks Gestational Age.

OBJECTIVE: To identify obstetric and neonatal risk factors associated with the development of germinal matrix-intraventricular hemorrhage (GM-IVH) in high-risk preterm neonates. METHODS AND PATIENTS: Data from 279 preterm infants (246 mothers) with a gestational age≤28+0 weeks admitted to our NICU between January 2004 and December 2009 were analyzed retrospectively. Occurrence of (GM-IVH) was diagnosed by using ultrasound and important clinical variables were extracted from the patient charts. Infants were divided into 2 groups: GM-IVH and non-GM-IVH. To account for multiple gestation, generalized estimation equations (GEE) were used for univariate analysis and for the evaluation of independent risk factors. RESULTS: A low 5-min APGAR-Score, multiple birth, low arterial blood pressure at NICU admission, hypercapnia during the first 72 h of life in life and absence of any antenatal corticosteroids were found to be significant independent risk factors in the development of GM-IVH. CONCLUSION: Preterm infants with low arterial blood pressure, absence of antenatal corticosteroids, low 5-min APGAR-Score, higher paCO2 within the first 3 days of life and multiple gestation were at higher risk to develop GM-IVH. Avoiding these risk factors may help to decrease the rate of GM-IVH.

[The Wolf-Hirschhorn Syndrome]. / Das Wolf-Hirschhorn Syndrom.

Wolf-Hirschhorn syndrome (WHS) represents a complex developmental disorder characterized by craniofacial dysmorphism, short stature, hypotonia, psychomotor retardation and seizures caused by a terminal deletion of the short arm of chromosome 4. Depending on the extent of the deletion, variable midline defects, abnormalities of the skeletal or urogenital system as well as the central nervous system are observed. Approximately 1/3 of the infants will die in the first year of life even though survival for more than 30 years has been reported. Due to current high quality standards of ultrasonography, WHS can often be diagnosed prenatally. We present a clinical case and provide an overview of the current literature.

The Cause of Acute Respiratory Failure Predicts the Outcome of Noninvasive Ventilation in Immunocompromised Children.

BACKGROUND: Noninvasive ventilation (NIV) may be superior to conventional therapy in immunocompromised children with respiratory failure. METHODS: Mortality, success rate, prognostic factors and side effects of NIV for acute respiratory failure (ARF) were investigated retrospectively in 41 in children with primary immunodeficiency, after stem cell transplantation or chemotherapy for oncologic disease. RESULTS: In 11/41 (27%) children invasive ventilation was avoided and patients were discharged from ICU. In children with NIV failure ICU-mortality was 19/30 (63%). 8/11 (72%) children with NIV success had recurrence of ARF after 27 days. Only 4/11 (36%) children with first episode NIV success and 8/30 (27%) with NIV failure survived to hospital discharge. Lower FiO2, SpO2/FiO2 and blood culture positive bacterial sepsis were predictive for NIV success, while fungal sepsis or culture negative ARF were predictive for NIV failure. We observed catecholamine treatment in 14/41 (34%), pneumothorax in 2/41 (5%), mediastinal emphysema in 3/41 (7%), a life threatening nasopharyngeal hemorrhage and need for resuscitation during intubation in 5/41 (12%) NIV-episodes. CONCLUSIONS: The prognosis of ARF in immunocompromised children remains guarded independent of initial success or failure of NIV due to a high rate of recurrent ARF. Reversible causes like bacterial sepsis had a higher NIV response rate. Relevant side effects of NIV were observed.

Automated adjustments of inspired fraction of oxygen to avoid hypoxemia and hyperoxemia in neonates - a systematic review on clinical studies.

Supplemental oxygen is commonly provided during transition of neonates immediately after birth. Whereas an initial FiO2 of 0.21 is now recommended to stabilize full-term infants in the delivery room, the best FiO2 to start resuscitation of the very low birth weight infant (VLBWI) immediately after delivery is currently not known. Recent recommendations include the use of pulse oximetry to titrate the use of supplemental oxygen. As reference values for pulse oximetry during the first minutes of life have become available, automated FiO2-adjustments are feasible and may be very useful for delivery room care to limit oxygen exposure. Beyond neonatal transition, preterm infants in the neonatal intensive care unit (NICU) commonly require supplemental oxygen to avoid hypoxemia, especially VLBWI receiving respiratory support because of poor respiratory drive and/or lung disease. For respiratory care of newborn infants in the NICU automated FiO2-adjustment systems have been developed and have been studied in preterm infants for limited time frames using short-term physiological outcomes. These studies could demonstrate short-term benefits such as more stable arterial oxygen saturation. Recent clinical trials have shown that oxygen targeting may significantly affect mortality and morbidity. Therefore, randomized controlled trials are needed to study the effects of automated FiO2-adjustment on long-term outcomes to prove possible benefits on survival, the rate of retino-pathy of prematurity and on neuro-development-al outcome.

[Treatment of neonatal asphyxia with a special focus on therapeutic hypothermia]. / Behandlung der neonatalen Asphyxie unter besonderer Berücksichtigung der therapeutischen Hypothermie.

In recent years the treatment of newborns for neonatal asphyxia has experienced a lot of new developments. A major milestone were the positive results of various trials for prophylactic treatment of hypoxic-ischemic encephalopathy by moderate cooling of the child or of his head. With this paper we attempt to provide a consented guideline to aid in the treatment decision for affected newborns and thus achieve a more homogeneous treatment strategy throughout Germany.

[Neurodevelopmental outcome of very low birth weight infants born at the Perinatal Centre in Ulm, Germany]. / Entwicklungsneurologische Nachuntersuchung von sehr unreifen Frühgeborenen im Perinatalzentrum Ulm.

BACKGROUND: Since 2006 an assessment of the neurodevelopmental outcome of very low birth weight infants (VLBWI) at a corrected age of 2 years is mandatory for every perinatal centre in Germany. The aim of our study was to check how complete these assessments were performed in our population of infants born at our perinatal centre and receiving treatment within our local neonatal network. Furthermore, the data obtained will be used for prenatal consultations. Another objective was to identify risk factors for adverse neurodevelopmental outcomes. METHODS: All VLBWI were invited for a follow-up exam using the Bayley Scales of Infant Development II (BSID-II) or III (BSID-III), or Griffiths Mental Developmental Scales) at 2 years corrected age. The results of children assessed by other institutions were collected. RESULTS: 142 (69.3%) of the 205 VLBWI, born and finally discharged alive at the perinatal centre in Ulm were assessed at a median (minimum - maximum) corrected age of 23 (18-27) months. The BSID-II Psychomotor Development Index (PDI) 91 was (< 50-128) (n=115), the BSID-II Mental Development Index (MDI) was 87 (< 50-134) (n=96), BSID-III MDI 95 (60-112) (n=29) and the Griffiths Score was 93 (67-140) (n=17). Severe disability was diagnosed in 36 (25.4%) of the children studied. Gestational age and higher grade intraventricular haemorrhage were associated independently with severe disability. CONCLUSIONS: It is very difficult to achieve a high rate of follow-up examinations in preterm infants <1,500 g in a neonatal network. Severe impairment in VLBWI is not rare. Improving neurodevelopmental outcome remains a challenge.

Effects of short sustained lung inflations on cerebral blood flow and cerebral tissue oxygenation in the juvenile rabbit.

BACKGROUND: Sustained lung inflations improve oxygenation but may impair hemodynamics. This study aimed to determine effects of short sustained inflations on cerebral blood flow and cerebral tissue oxygenation in experimental lung injury. METHODS: Experiments were performed in 6 juvenile ventilated New Zealand white rabbits. The effects of a series of sustained inflations at 20, 25 and 30 cmH2O pressure for 15 seconds duration each on hemodynamics, cerebral blood flow and cerebral tissue oxygenation were determined by laser Doppler flowmetry and cerebral tissue oxygen tension measurement in naive animals, after surfactant depletion and subsequent fluid filling of the lung. RESULTS: During the series of sustained inflations the mean arterial blood pressure decreased by 73%, 52% and 32% and the mean cerebral blood flow decreased by 73%, 39% and 30% in naive animals, after surfactant depletion and with fluid filling of the lung respectively. Arterial oxygen saturation was maintained or increased, while mean cerebral tissue oxygenation decreased by 48% (naive), 8% (surfactant depletion) or increased by 81% (surfactant depletion and fluid filling). Three minutes after the sustained inflations blood gases were similar to the blood gases prior to the sustained inflations. CONCLUSION: A series of short sustained lung inflations of 15 seconds duration can impair cerebral blood flow but increase arterial oxygen saturation in this juvenile animal model. The combination of these effects resulted in either a decrease or increase in regional cerebral tissue oxygenation.

Brain oxygenation monitoring during neonatal resuscitation of very low birth weight infants.

OBJECTIVE: To explore if regional cerebral tissue oxygen saturation monitoring by near-infrared spectroscopy (NIRS) is feasible during neonatal resuscitation of very low birth weight (VLBW) infants after birth. STUDY DESIGN: Cerebral tissue oxygen saturation was measured by NIRS in 51 VLBW infants (mean gestational age: 27.8 weeks) during the first 10 min after delivery. RESULT: A regional cerebral tissue oxygen saturation signal was available after a median (interquartile range) age of 52 (44 to 68) s. In three infants the signal was obtained after 10 min of age. After delivery cerebral tissue oxygen saturation rose continuously from 37 (31 to 49) % at 1 minute of age and reached a steady state in the range of 61 to 84% ∼7 min after birth. Percentiles of cerebral tissue oxygen saturation of this cohort of preterm infants are given. CONCLUSION: Cerebral tissue oxygen saturation monitoring is feasible during neonatal resuscitation of VLBW infants within the first minutes of life.

Predictors of early nasal CPAP failure and effects of various intubation criteria on the rate of mechanical ventilation in preterm infants of <29 weeks gestational age.

INTRODUCTION: Delivery room management using early nasal continuous positive airway pressure (nCPAP) may delay surfactant therapy. OBJECTIVE: To identify factors associated with early nCPAP failure and effects of various intubation criteria on rate and time of intubation. DESIGN: Retrospective analysis of the first 48 h in infants of 23-28 weeks gestational age (GA) treated with sustained inflations followed by early nCPAP. RESULTS: Of 225 infants (GA 26.2±1.6 weeks) 140 (62%) could be stabilised with nCPAP in the delivery room, of whom 68 (49%; GA 26.9±1.5 weeks) succeeded on nCPAP with favourable outcome and 72 infants (51%; GA 26.3±1.4 weeks) failed nCPAP within 48 h at a median (IQR) age of 5.6 (3.3-19.3) h. History or initial blood gases were poor predictors of subsequent nCPAP failure. Intubation at fraction of inspired oxygen (FiO(2))≥0.35 versus 0.4 versus 0.45 instead of ≥0.6 would have resulted in unnecessary intubations of 16% versus 9% versus 6% of infants with nCPAP success but decreased the age at intubation of infants with nCPAP failure to 3.1 (2.2-5.2) versus 3.8 (2.5-8.7) versus 4.4 (2.7-10.9) h. CONCLUSIONS: Medical history or initial blood gas values are poor predictors of subsequent nCPAP failure. A threshold FiO(2) of ≥0.35-0.45 compared to ≥0.6 for intubation would shorten the time to surfactant delivery without a relevant increase in intubation rate. An individualised approach with a trial of early nCPAP and prompt intubation and surfactant treatment at low thresholds may be the best approach in very low birthweight infants.

[Mortality of extremely low birthweight infants - large differences between quality assurance data and the national birth/death registry]. / Mortalität sehr unreifer Frühgeborener - Erhebliche Diskrepanz zwischen Neonatalerhebung und amtlicher Geburten-/Sterbestatistik.

BACKGROUND: To evaluate neonatal outcome, the German neonatal quality assurance dataset is often used. However, a systematic bias may occur, as not all live births are registered in this dataset. The aim of our study was to evaluate the magnitude of this systematic error by comparing this dataset to the national birth/death registry. METHODS: The summary statistics of live births and deaths with a birthweight <1 500 g from the quality assurance datasets 2007-2009 of 5 German States (Baden-Württemberg, Bavaria, Hesse, Lower-Saxony and North Rhine-Westfalia) were compared with the dataset from the national birth/death registry. RESULTS: Our analysis included 68% of the German birth cohort 2007-2009. The quality assurance dataset included 1 151 of 1 716 neonatal deaths (67.1%) in infants with a birthweight <1,000 g registered within the national birth/death registry; 565 deaths were missing. A total of 277 of 303 deaths (94.1%) with a birthweight 1,000-1,499 g were registered; 26 deaths were missing. In the state of Baden-Württemberg up to 11% more infants were registered in the quality assurance dataset than in the national registry, but an average of 36 neonatal deaths/year with a birthweight <1,000 g were missing (63.4% registration rate). CONCLUSION: This analysis shows that the quality assurance data miss more than 1/3 of deaths in extremely low birthweight infants. Transfers between hospitals may result in multiple data entries and additional bias. Comparing outcome statistics based on the neonatal quality assurance dataset may lead to a substantial systematic error. Linkage to national birth and death certificates and/or to the perinatal dataset is urgently needed.

Delivery room management of very low birth weight infants in Germany, Austria and Switzerland--a comparison of protocols.

BACKGROUND: Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, <1500g) at birth, despite regularly updated international guidelines. OBJECTIVE: To investigate protocols for DR management of VLBWI in Germany, Austria and Switzerland and to compare these with the 2005 ILCOR guidelines. METHODS: DR management protocols were surveyed in a prospective, questionnaire-based survey in 2008. Results were compared between countries and between academic and non-academic units. Protocols were compared to the 2005 ILCOR guidelines. RESULTS: In total, 190/249 units (76%) replied. Protocols for DR management existed in 94% of units. Statistically significant differences between countries were found regarding provision of 24 hr in house neonatal service; presence of a designated resuscitation area; devices for respiratory support; use of pressure-controlled manual ventilation devices; volume control by respirator; and dosage of Surfactant. There were no statistically significant differences regarding application and monitoring of supplementary oxygen, or targeted saturation levels, or for the use of sustained inflations. Comparison of academic and non-academic hospitals showed no significant differences, apart from the targeted saturation levels (SpO2) at 10 min. of life. Comparison with ILCOR guidelines showed good adherence to the 2005 recommendations. SUMMARY: Delivery room management in German, Austrian and Swiss neonatal units was commonly based on written protocols. Only minor differences were found regarding the DR setup, devices used and the targeted ranges for SpO2 and FiO2. DR management was in good accordance with 2005 ILCOR guidelines, some units already incorporated evidence beyond the ILCOR statement into their routine practice.

[EuroNeoStat: a European information system on the outcomes of care for very-low-birth-weight infants (< 1500 g)]. / EuroNeoStat: ein Europäisches Informationssystem zur erfassung der behandlungsergebnisse von sehr untergewichtigen Frühgeborenen mit einem Geburtsgewicht < 1500 g.

BACKGROUND: Prematurity rates are increasing throughout the world. Despite an overall rather small percentage of very low birth weight infants (VLBWI), which is approx. 1-2 % in most countries, these infants contribute significantly to morbidity and neonatal and infant mortality rates. METHODS: EuroNeoStat was initiated as an European information system on the outcomes of VLBWI to monitor and improve the care of these infants throughout Europe. EuroNeoStat includes an initiative, called EuroNeoSafe, to promote the safety of these high risk preterm infants. Perinatal and neonatal data from VLBWI is collected without using data that identify individuals or institutions. These data is analyzed at the coordination center in Bilbao. All institutions taking care on VLBWI in Europe can participate in this network and will be able to compare their own outcome data with other institutions from the network. Information on EuroNeoStat and the current data set is available on www.euroneostat.org. CONCLUSION: Successful initiatives aiming at improving outcomes in perinatal and neonatal care require collaborative networking, an attitude of constructive criticism and thorough comparative analysis of the outcomes and incidents in the health-care process.

Surgery without assistance in newborns and infants with hydrocephalus and neural tube defects.

Standard neurosurgical procedures for hydrocephalus and open neural tube defects in newborns and infants under 6 months of age were performed by a single neurosurgeon on his own without the help of an assistant or scrub nurse. The objective of this study was to assess the outcome of these procedures in terms of operating time, the presence of bacterial infection, and wound healing. Between 2001 and 2004, a total of 126 procedures were performed on 82 patients under 6 months of age. We observed 1 bacterial and 2 fungal infections. Two infections had already been detected at the beginning of the surgical procedure in cerebrospinal fluid (CSF) specimens obtained from children with Candida ventriculitis. The other infection occurred after leakage of CSF from a myelomeningocele 10 days after initial surgery. Our study suggests that excellent results can be achieved in standard neurosurgical procedures without assistance even in high-risk newborns and infants if resource or other constraints require such an unconventional approach.

[Data collection for quality assurance in neonatology: how do physicians compare to documentation specialists?]. / Datenerhebung für die Qualitätssicherung in der Neonatologie. Wer dokumentiert genauer: Arzte oder spezielle Dokumentationskräfte?

BACKGROUND: The quality of data collected for the German nationwide quality assurance program in neonatology is currently unknown. The aim of this study was to compare the quality of data collected by resident physicians with the quality of similar data collected by a dedicated research nurse. METHODS: Data for the German national quality assurance program in neonatology, derived from a cohort of 128 premature newborns with a birth weight <1500 g and/or a gestational age of <30 weeks born in the year 2003, were collected by residents taking care on these patients, and separately by a dedicated research nurse for the European Neonatal Network (EuroNeoNet). The data set collected for both networks included 44 common data items. The two data sets were compared, and any disagreement was double-checked using the chart of the baby to clarify which of the data entries was wrong. Furthermore, as data items are not equally important, a weighted analysis of all mistakes was performed. RESULTS: We found wrong data in 108/128 (84 %) of the data sets collected by the residents, and in 43/128 (34 %) of the data sets collected by the research nurse (p < 0.001). The weighted analysis revealed that residents made more mistakes in 30/44 of collected data items, whereas the research nurse did worse only in 1/44 data items. CONCLUSION: This study shows that the quality of data obtained by our resident physicians was worse than the quality of data obtained by our dedicated research nurse.

[Mortality and morbidity of very premature infants in Baden-Württemberg depending on hospital size. Is the current degree of regionalization adequate?]. / Mortalität und Morbidität sehr unreifer Frühgeborener in Baden-Württemberg in Abhängigkeit von der Klinikgrösse. Ist der derzeitige Grad der Regionalisierung ausreichend?

BACKGROUND: Regionalization of perinatal and neonatal care improves outcome. The aim of this study was to compare outcome in preterm infants with a gestational age (GA) < 32 weeks in relation to patient volume. METHODS: Outcome data from the state-wide neonatal quality assurance system from 2003 - 2004 from all infants treated in one of the five largest perinatal centers in Baden-Wuerttemberg were subtracted from the total dataset. Data derived from these five centers was compared with data from all other remaining NICU's in the state. RESULTS: Mortality was 33.3 % vs. 15.0 % (other NICU's vs. five perinatal centers; p < 0.001) for infants < 26 weeks GA, 11.4 % vs. 8.9 % (n. s.) for infants 26 - 27 weeks GA, and 2.5 % vs. 3.5 % (n. s.) for infants 28 - 31 weeks GA. When analyzed as one group of infants < 28 weeks GA, mortality was 20.1 vs. 12.1 % (p = 0.003). The rate of intraventricular hemorrhage degrees III-IV was 30.2 % vs. 18.6 % (p = 0.015) for infants < 26 weeks GA, 14.5 % vs. 10.2 % (n. s.) for infants 26 - 27 weeks GA, and 2.9 % vs. 2.5 % (n. s.) for infants 28 - 31 weeks GA. The rate of periventricular leukomalacia was 11.3 % vs. 6.7 % (p = 0.18) for infants < 26 weeks GA, 6.1 % vs. 2.8 % (n. s.) for infants 26 - 27 weeks GA, and 2.8 % vs. 2.3 %; (n. s.) for infants 28 - 31 weeks GA. CONCLUSION: This study supports the hypothesis, that regionalization of neonatal care for very immature infants to few perinatal centers with a large case load may improve survival of these infants, and may reduce morbidity, associated with long-term sequelae.