Neonatologie/Pädiatrie – Leitlinie Parenterale Ernährung, Kapitel 13

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.Eine besondere Herausforderung bei der Durchführung parenteraler Ernährung (PE) bei pädiatrischen Patienten ergibt sich aus der großen Spannbreite zwischen den Patienten, die von extrem unreifen Frühgeborenen bis hin zu Jugendlichen mit einem Körpergewicht von mehr als 100 kg reicht, und ihrem unterschiedlichen Substratbedarf. Dabei sind alters- und reifeabhängige Veränderungen des Stoffwechsels sowie des Flüssigkeits- und Nährstoffbedarfs zu berücksichtigen sowie auch die klinische Situation, in der eine PE eingesetzt wird. Das Vorgehen unterscheidet sich deshalb ganz erheblich von der PE-Praxis bei erwachsenen Patienten, z.B. ist der Flüssigkeits-, Nährstoff- und Energiebedarf von Früh- und Neugeborenen pro kg Körpergewicht höher als bei älteren pädiatrischen und bei erwachsenen Patienten. In der Regel benötigen alle Frühgeborenen <35. SSW und alle kranken Reifgeborenen während der Phase des allmählichen Aufbaus der enteralen Nahrungszufuhr eine vollständige oder partielle PE. Die Zufuhrmengen der PE bei Neonaten müssen berechnet (nicht geschätzt) werden. Der Anteil der PE sollte zur Minimierung von Nebenwirkungen sobald wie möglich durch Einführung einer enteralen Ernährung vermindert (teilparenterale Ernährung) und schließlich komplett durch enterale Ernährung abgelöst werden. Eine unangemessene Substratzufuhr im frühen Säuglingsalter kann langfristig nachteilige Auswirkungen im Sinne einer metabolischen Programmierung des Krankheitsrisikos im späteren Lebensalter haben. Wenn bei älteren Kindern und Jugendlichen dagegen der Energie- und Nährstoffbedarf eines Patienten im Vorschul- oder Schulalter durch eine enterale Nährstoffzufuhr nicht gedeckt werden kann, ist abhängig von Ernährungszustand und klinischen Umständen spätestens innerhalb von 7 Tagen eine partielle oder totale PE zu erwägen

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia

A proof of concept study of respiratory physiology in preterm neonates during high flow nasal cannula therapy

PhD ThesisIntroduction and rationale: High flow nasal cannula therapy is being increasingly used as a form of respiratory support across the world. Its adoption and popularity have been rapid but little is known regarding its key mechanism of action even after more than a decade of its use. I conducted a proof of concept study of respiratory physiology during high flow therapy in preterm neonates. Methods: The study protocol involved measurement of nasopharyngeal airway pressures and gas concentrations as well as measurement of tidal breathing indices. A detailed descriptive review of clinical efficacy of high flow nasal cannula in preterm infants was performed. In order to identify the optimum measuring techniques, in this proof of concept study, three types of pressure measuring techniques, a gas analyser device and a non-invasive tidal breathing indices device were studied and the results are presented in this thesis. In addition, a detailed protocol for a larger randomised crossover study of respiratory physiology during continuous positive airway pressure of 6 cm H2O and high flow nasal cannula therapy ranging from 2-8 litres per minute flow was designed.. Results: In this thesis, the results of a proof of concept physiological study have been presented. The results of the measurements performed in six babies of varying gestational age (less than 37 weeks of gestation) and birth weight are presented. Valid tidal volumes were measured in all babies, nasopharyngeal gas concentrations and pressure measurements in five and two babies respectively. There were no adverse events. Conclusions: It is feasible to measure nasopharyngeal air way pressures and gas concentrations as well as non-invasive tidal breathing indices in babies on high flow nasal cannula therapy safely. This study was successfully followed up by a larger randomised cross over study involving 45 infants with the same protocol.Special Trustees at Newcastle Hospital

Respiratory Care of the Neonate

The respiratory distress is a very common condition both in term and in preterm neonates and the most frequent reason for admission to the neonatal intensive care unit (NICU). The aetiology greatly depends on the maturation of neonate’s organs and perinatal events. The clinical picture is sometimes scarce and very nonspecific for the etiologic determination. Treatment of neonatal RD begins first with the application of a mixture of oxygen and air, then with different modes of non-invasive respiratory support methods. Non-invasive respiratory support can be sustained with nasal continuous positive airway pressure, bi-level positive airway pressure and high-flow nasal cannula ventilation. Non-invasive ventilation with high-frequency oscillations through nasal cannula or masks is also possible with some respiratory devices. Non-invasive ventilation is usually combined with the application of natural surfactant and other therapeutic means, like methylxanthine therapy, prevention and closure of patent ductus arteriosus, and control of infection. In the case of non-invasive ventilation failure, different kinds of invasive ventilation methods are available and being practiced in NICUs. The invasive respiratory support can be maintained by controlled or intermittent mandatory ventilation combined with different supportive synchronous positive inspiratory ventilation, offered by modern respirators

Physiopathological rationale of using high-flow nasal therapy in the acute and chronic setting: A narrative review

Chronic lung disease and admissions due to acute respiratory failure (ARF) are becoming increasingly common. Consequently, there is a growing focus on optimizing respiratory support, particularly non-invasive respiratory support, to manage these conditions. High flow nasal therapy (HFNT) is a noninvasive technique where humidified and heated gas is delivered through the nose to the airways via small dedicated nasal prongs at flows that are higher than the rates usually applied during conventional oxygen therapy. HFNT enables to deliver different inspired oxygen fractions ranging from 0.21 to 1. Despite having only recently become available, the use of HFNT in the adult population is quite widespread in several clinical settings. The respiratory effects of HNFT in patients with respiratory failure may be particularly relevant for clinicians. In this narrative review, we discuss the main pathophysiological mechanism and rationale for using HFNT in the acute and chronic setting

An injection and mixing element for delivery and monitoring of inhaled nitric oxide

Background Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used primarily in the critical care setting for patients concurrently supported by invasive or noninvasive positive pressure ventilation. NO delivery devices interface with ventilator breathing circuits to inject NO in proportion with the flow of air/oxygen through the circuit, in order to maintain a constant, target concentration of inhaled NO. Methods In the present article, a NO injection and mixing element is presented. The device borrows from the design of static elements to promote rapid mixing of injected NO-containing gas with breathing circuit gases. Bench experiments are reported to demonstrate the improved mixing afforded by the injection and mixing element, as compared with conventional breathing circuit adapters, for NO injection into breathing circuits. Computational fluid dynamics simulations are also presented to illustrate mixing patterns and nitrogen dioxide production within the element. Results Over the range of air flow rates and target NO concentrations investigated, mixing length, defined as the downstream distance required for NO concentration to reach within ±5 % of the target concentration, was as high as 47 cm for the conventional breathing circuit adapters, but did not exceed 7.8 cm for the injection and mixing element. Conclusion The injection and mixing element has potential to improve ease of use, compatibility and safety of inhaled NO administration with mechanical ventilators and gas delivery devices

Physiological, biochemical, and biophysical characterization of the lung-lavaged spontaneously-breathing rabbit as a model for respiratory distress syndrome

Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant

Event program

UNLV Undergraduates from all departments, programs and colleges participated in a campus-wide symposium on April 16, 2011. Undergraduate posters from all disciplines and also oral presentations of research activities, readings and other creative endeavors were exhibited throughout the festival

Heliox for croup in children (Review)

Background: Croup is thought to be triggered by a viral infection and is characterised by respiratory distress due to upper airway inflammation and swelling of the subglottic mucosa in children. Mostly it is mild and transient and resolves with supportive care. In moderate to severe cases, treatment with corticosteroids and nebulised epinephrine (adrenaline) is required. Corticosteroids improve symptoms but it takes time for a full effect to be achieved. In the interim, the child is at risk of further deterioration. This may rarely result in respiratory failure necessitating emergency intubation and ventilation. Nebulised epinephrine may result in dose-related adverse effects including tachycardia, arrhythmias and hypertension and its benefit may be short-lived. Helium-oxygen (heliox) inhalation has shown therapeutic benefit in initial treatment of acute respiratory syncytial virus (RSV) bronchiolitis and may prevent morbidity and mortality in ventilated neonates. Heliox has been used during emergency transport of children with severe croup and anecdotal evidence suggests that heliox relieves respiratory distress. Objectives: To examine the effect of heliox on relieving symptoms and signs of croup, as determined by a croup score (a tool for measuring the severity of croup).To examine the effect of croup on rates of admission or intubation (or both), through comparisons of heliox with placebo or any active intervention(s) in children with croup. Search methods: We searched CENTRAL 2013, Issue 10, MEDLINE (1950 to October week 5, 2013), EMBASE (1974 to November 2013), CINAHL (1982 to November 2013), Web of Science (1955 to November 2013) and LILACS (1982 to November 2013). In addition, we searched two clinical trials registries: the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and clinicaltrials.gov (searched 12 November 2013). Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing the effect of helium-oxygen mixtures with placebo or any active intervention(s) in children with croup. Data collection and analysis: Two review authors independently identified and assessed citations for inclusion. A third review author resolved disagreements. We assessed included trials for allocation concealment, blinding of intervention, completeness of outcome data, selective outcome reporting and other potential sources of bias. We reported mean differences for continuous data and odds ratios for dichotomous data. We descriptively reported data not suitable for statistical analysis. Main results: We included three RCTs with a total of 91 participants. One study compared heliox 70%/30% with 30% humidified oxygen administered for 20 minutes in children with mild croup and found no statistically significant differences in the overall change in croup scores between heliox and the comparator. In another study, children with moderate to severe croup were administered intramuscular dexamethasone 0.6 mg/kg and either heliox 70%/30% with one to two doses of nebulised saline, or 100% oxygen with one to two doses of nebulised racaemic epinephrine for three hours. In this study, the heliox group's croup scores improved significantly more at all time points from 90 minutes onwards. However, overall there were no significant differences in croup scores between the groups after four hours using repeated measures analysis. In a third study, children with moderate croup all received one dose of oral dexamethasone 0.3 mg/kg with heliox 70%/30% for 60 minutes in the intervention group and no treatment in the comparator. There was a statistically significant difference in croup scores at 60 minutes in favour of heliox but no significant difference after 120 minutes. It was not possible to pool outcomes because the included studies compared different interventions and reported different outcomes. No adverse events were reported. Authors' conclusions: There is some evidence to suggest a short-term benefit of heliox inhalation in children with moderate to severe croup who have been administered oral or intramuscular dexamethasone. In one study, the benefit appeared to be similar to a combination of 100% oxygen with nebulised epinephrine. In another study there was a slight change in croup scores between heliox and controls, with unclear clinical significance. In another study in mild croup, the benefit of humidified heliox was equivalent to that of 30% humidified oxygen, suggesting that heliox is not indicated in this group of patients provided that 30% oxygen is available. Adequately powered RCTs comparing heliox with standard treatments are needed to further assess the role of heliox in children with moderate to severe croup