Lung-protective ventilatory strategies in intubated preterm neonates with RDS.

This article provides a narrative review of lung-protective ventilatory strategies (LPVS) in intubated preterm infants with RDS. A description of strategies is followed by results on short-and long-term respiratory and neurodevelopmental outcomes. Strategies will include patient-triggered or synchronized ventilation, volume targeted ventilation, the technique of intubation, surfactant administration and rapid extubation to NCPAP (INSURE), the open lung concept, strategies of high-frequency ventilation, and permissive hypercapnia. Based on this review single recommendations on optimal LPVS cannot be made. Combinations of several strategies, individually applied, most probably minimize or avoid potential serious respiratory and cerebral complications like bronchopulmonary dysplasia and cerebral palsy.

Neonatal Ureaplasma urealyticum colonization increases pulmonary and cerebral morbidity despite treatment with macrolide antibiotics.

OBJECTIVE: To evaluate the influence of Ureaplasma urealyticum (UU) colonization on neonatal pulmonary and cerebral morbidity. METHODS: Single-center case-control study including all preterm infants with positive UU tracheal colonization between 1990 and 2012. Cases were matched with controls by birth year, gestational age, birth weight, and sex. All cases had received macrolide antibiotics for UU infection starting at the time of first positive culture results from tracheal aspirates. Main outcome parameters included presence and severity of hyaline membrane disease (IRDS), duration of ventilation, bronchopulmonary dysplasia at 36 postmenstrual age and neurological morbidities (seizures, intra-/periventricular hemorrhages-I/PVH, periventricular leukomalacia-PVL). RESULTS: Of 74 cases identified 8 died and 4 had to be excluded; thus, 62 preterm infants were compared to 62 matched controls. UU was significantly associated with IRDS (79 vs. 61 %, p = 0.015), BPD (24 vs. 6 %, p = 0.003), seizures (23 vs. 5 %, p = 0.002) and I/PVH (45 vs. 24 %, p = 0.028). Cases had longer duration of mechanical ventilation and total duration of invasive and non-invasive ventilation (median 11 vs. 6 days p = 0.006 and 25 vs. 16.5 days p = 0.019, respectively). CONCLUSION: UU was found to be significantly associated with pulmonary short- and long-term morbidity and mild cerebral impairment despite treatment with macrolide antibiotics.

Evaluation of bedside pulmonary function in the neonate: From the past to the future.

Pulmonary function testing and monitoring plays an important role in the respiratory management of neonates. A noninvasive and complete bedside evaluation of the respiratory status is especially useful in critically ill neonates to assess disease severity and resolution and the response to pharmacological interventions as well as to guide mechanical respiratory support. Besides traditional tools to assess pulmonary gas exchage such as arterial or transcutaenous blood gas analysis, pulse oximetry, and capnography, additional valuable information about global lung function is provided through measurement of pulmonary mechanics and volumes. This has now been aided by commercially available computerized pulmonary function testing systems, respiratory monitors, and modern ventilators with integrated pulmonary function readouts. In an attempt to apply easy-to-use pulmonary function testing methods which do not interfere with the infant́s airflow, other tools have been developed such as respiratory inductance plethysmography, and more recently, electromagnetic and optoelectronic plethysmography, electrical impedance tomography, and electrical impedance segmentography. These alternative technologies allow not only global, but also regional and dynamic evaluations of lung ventilation. Although these methods have proven their usefulness for research applications, they are not yet broadly used in a routine clinical setting. This review will give a historical and clinical overview of different bedside methods to assess and monitor pulmonary function and evaluate the potential clinical usefulness of such methods with an outlook into future directions in neonatal respiratory diagnostics.

Meconium aspiration syndrome--a 21-years' experience from a tertiary care center and analysis of risk factors for predicting disease severity.

Aim of this study was to describe the course of perinatal factors in neonates with meconium aspiration syndrome (MAS) from 1990 to 2010 and to determine risk factors for a severe course of the disease.All neonates with MAS hospitalized in our level III neonatal intensive care unit from 1990 to 2010.Retrospective analysis of trends of perinatal factors in neonates with MAS over time and of the association of these factors with severe MAS (need for invasive mechanical ventilation for ≥7 days, or need for high frequency oscillation or need for extracorporeal membrane oxygenation).We included 205 neonates with MAS, 55 had severe MAS (27%). MAS incidence and absolute number of MAS cases per year decreased during the observation period (p=0.003 and 0.005, respectively) as well as rates of outborn deliveries (p=0.004), duration of invasive mechanical ventilation (p=0.004), and hospital stay (p=0.036). Incidence and absolute number of severe MAS cases per year decreased (p=0.008 and 0.006, respectively), though the percentage of severe MAS among all neonates with MAS did not change. Risk factors for severe MAS were acute tocolysis (odds ratio 18.2 (95% confidence interval 2.1-155.3), p<0.001) fetal distress (3.4 (1.8-6.4), p<0.001), and severe and moderate birth asphyxia (4.4 (2.0-9.7), p=0.001 and 2.9 (1.5-5.6), p=0.009).The incidence and absolute numbers of MAS and severe MAS cases changed during the study period as well as neonatal management. Acute tocolysis, fetal distress, and asphyxia were associated with severe MAS.

[Pneumothorax during mechanical ventilation--therapeutic options in term and preterm neonates]. / Pneumothorax unter Beatmung--ein Vergleich möglicher Therapieoptionen bei Reif- und Frühgeborenen.

A pneumothorax (PTX) is a potentially life threatening event during mechanical ventilation. Aim of this study was to analyse 3 different ways of management: expectant treatment, once-only pleural puncture and thoracic drainage.Retrospective data analysis in term and preterm neonates admitted to the NICU of the Medical University of Graz (between 2000-2010) and Innsbruck (2002-2010) who suffered from a PTX during continuous positive airway pressure (CPAP) or conventional mechanical ventilation (CMV).104 neonates, 33 term and 71 preterm neonates with PTX were included. 33 term neonates: 52% were treated expectantly, 36% with thoracic drainage and 12% with once-only pleural puncture (100% thoracic drainage after pleural puncture). 71 preterm neonates: 25% were treated expectantly, 52% with thoracic drainage and 23% with pleural puncture (63% thoracic drainage after pleural puncture). In CPAP-subgroup (n=64), term neonates were treated in 60% expectantly and in 40% with thoracic drain-age, preterm neonates in 33% expectantly, in 47% with thoracic drainage and in 20% with pleural puncture (50% thoracic drainage after pleural puncture). In CMV-subgroup (n=40), term neonates were treated in 44% expectantly, in 33% with thoracic drainage and in 22% with pleural puncture (100% thoracic drainage after pleural puncture), preterm neonates in 9% expectantly, in 64% with thoracic drainage and in 27% with pleural puncture (83% thoracic drain-age after pleural puncture).Present data show that expectant treatment is feasible. If invasive intervention is needed, once-only pleural puncture was not successful, as often thoracic drainage was necessary in addition.

Multi-modal approach to prophylaxis of necrotizing enterocolitis: clinical report and review of literature.

For the first time a multimodal approach to NEC prophylaxis is reported, consisting of early trophic feeding with human breast milk, and enteral administration of an antibiotic, an antifungal agent, and probiotics. A retrospective analysis of local protocol of NEC prophylaxis is presented. Included were all VLBWI admitted to the NICU, including transfers within the first 28 days of life. These infants were divided into two groups, an "inborn group" (infants admitted within the first 24 h of life) and an "outborn group" (infants admitted after the onset of their second day of life). Prophylaxis of NEC according to protocol was started at the day of admission, and was continued until discharge. Between 1998 and 2004, 405 VLBWI were admitted, including all transfers within the first 28 days of life. A total of 334 (82%) infants were admitted within the first 24 h of life (inborn group), and 71 (18%) were admitted after 24 h of life (outborn group). Five infants developed clinical features of necrotizing enterocolitis. The inborn group showed a NEC incidence of 0.7% (two infants), whereas the outborn group showed a NEC incidence of 4.5% (three infants), respectively. This difference was significant (P=0.049, Fisher's exact test). A surgical treatment with bowel resection was performed in two infants (both from the outborn group). The present study used a combination of different strategies, all having shown to have some beneficial effect, but not having brought a clinical breakthrough in single administration studies. Combinated were the beneficial effects of human breast milk feeding, oral antiobiotics, oral antifungal agents, and the administration of probiotics. In a homogenous group of preterm infants, using this protocol of multimodal NEC prophylaxis, there was a very low incidence of NEC, when started within the first 24 h of life.

[Inhalation therapy with nitric oxide in pulmonary hypertension: Comparison of preterm infants versus newborn infants]. / Inhalative Therapie mit Stickstoffmonoxid bei pulmonaler Hypertension: Vergleich des Effektes bei Früh- und Neugeborenen.

BACKGROUND: Inhaled nitric oxide (iNO) is used as a vasodilator in pulmonary hypertension (PH) of the newborn infant. PATIENTS AND METHODS: Retrospective analysis of patients, who were treated at our department with iNO in the period from 1994-2001. Response was defined as an increase of the paO (2)/FiO (2) Ratio > or = 20 % and/or a decrease of the oxygenation index (OI) >/= 20 % after 2 h (early response), and consecutively after 24 h (late response). The patients were divided into a) primary persistent pulmonary hypertension of the newbom (PPHN), or b) pulmonary hypertension secondary to meconium aspiration syndrome (MAS), sepsis or congenital diaphragmatic hernia (CDH). RESULTS: Between 1994 and 2001 we treated 47 patients with iNO at our neonatal intensive care unit. We included 16 (35 %) preterm infants (GA 34,5 [25 - 37] weeks, GG 2061 [680 - 3410] g) (Median/Range) and 31 (65 %) newbom (GA 40 [38 - 42] weeks, GG 3510 [2550 - 4560] g). 18 (38 %) patients suffered from primary PPHN, 29 (62 %) from secondary PPHN (14 MAS [30 %], 8 sepsis [17 %], 4 CDH [8 %]). 8 (50 %) preterm and 20 (64 %) term infants showed a positive iNO response after 2 h, again 8 (50 %) preterm and 20 (64%) term infants showed a positive iNO response after 24 h. There was neither a significant difference between term and preterm infants at 2 h, nor at 24 h. Between 2 h and 24 h 10 patients changed in their response to iNO. 5 (18 %) patients with early response showed a significant degradation after 24 h, whereas 5 (26 %) of the patients without early response showed a significant improvement of the oxygenation alter 24 h. Alltogether 13 (72 %) patients with PPHN, 8 (57 %) with MAS, 2 (50 %) with CDH, 4 (50 %) with sepsis showed a positive iNO response after 24 h. In regard to the oxygenation parameters at start of iNO-therapy, the patients with early response did not differ from the patient without response (median OI: 20,0 versus 21,8, median paO (2)/FiO (2) Ratio: 59,3 versus 55,0 mmHg at the start of the iNO therapy). CONCLUSION: In regard to iNO response, there was no significant difference between term and preterm infants. Due to the changing response, a positive iNO-response after 2 h had no predictive value for the further prognosis of the oxygenation situation under iNO therapy.

Assessment of the single-occlusion technique for measurements of respiratory mechanics and respiratory drive in healthy term neonates using a commercially available computerized pulmonary function testing system.

In this study, a critical assessment of the single-occlusion technique as a means of measuring passive respiratory mechanics and respiratory drive (P0.1) was performed in nonintubated spontaneously breathing healthy term neonates using commercially available computerized equipment (PEDS system). In general, we found that quality parameters only partially conformed to the international established standards for measuring passive respiratory mechanics. There was a failure rate of technically acceptable occlusions of about 50% for respiratory mechanics measurements and 20% for P0.1 measurements. Intersubject variability of the data was between 10 and 40%. After studying different lengths of occlusion times (Tocc; 0.2, 0.3, 0.4 and 0.5 s), it was found that acceptable occlusions for passive respiratory mechanics were obtained only if the expiratory Tocc exceeded 0.2 s. Increasing the Tocc had no effect on the absolute values of respiratory mechanics but showed a significant trend towards more technically acceptable occlusions. We speculate that a Tocc of at least 0.4 s may be a prerequisite for obtaining reliable results for respiratory mechanics in healthy term neonates.

[Respiratory management of in neonatal intensive care]. / Respiratorisches Management intensivgepflegter Neugeborener.

This paper gives an critical overview over different therapies for the management of neonates with respiratory failure. Several, partially revolutionary, new therapies have been introduced in the clinical routine in the last 10 to 15 years like surfactant therapy, inhalation of nitric oxide, extracorporeal membrane oxygenation and high frequency oscillatory ventilation. Furthermore, there are new promising ventilatory techniques like pressure support ventilation, proportional assist ventilation or liquid ventilation in clinical testing.

[Blueberry muffin baby: the pathogenesis of cutaneous extramedullary hematopoiesis]. / Blueberry-Muffin-Baby. Zur Pathogenese der kutanen extramedullären Hämatopoese.

Two neonates exhibited the clinical picture of the "blueberry muffin baby" at delivery. The integument manifested petechiae and purpuric magenta-colored macules, papules, and plaques, as well as blueberry-colored ecchymoses. These findings led to the diagnosis of a connatal cytomegalovirus infection and fetal erythroblastosis, respectively. The hemorrhagic-purpuric looking skin lesions reflected extramedullary hematopoiesis with ultrastructural study disclosing evidence of both erythro- and granulopoietic lineage. For the first time, we were able to demonstrate that complexes of red cells in various stages of maturation can occur in the skin, similarly to the erythroblastic islands of the bone marrow. In the pathogenesis of extramedullary hematopoiesis, mechanisms underlying the reconstitution of blood cells must be considered. These may reactivate hematopoiesis in organs where it previously occurred in embryonic and fetal life. Possible causative factors may be great compensatory demand, deficient replacement, or loss or dysfunction of corpuscular blood elements. This would explain the occurrence of this disease entity in conjunction with etiologically completely heterogeneous systemic diseases.

Changes in cerebral blood volume and cerebral oxygenation during periodic breathing in term infants.

The present study is an analysis of changes in cerebral oxygenation and cerebral blood volume (CBV) during periodic breathing in healthy term infants by means of near infrared spectroscopy (NIRS). Polygraphy included electrocardiogram, electrooculogram, heart rate, oxygen saturation, side stream capnography, two respiratory effort sensors, a movement sensor, and NIRS. During periodic breathing analysis of behaviour of total haemoglobin (cHbtot), deltaCBV, the haemoglobin oxygenation index (cHbD), and cytochrome oxidase (CytOx) was performed. In ten healthy term infants 30 cycles of periodic breathing with a mean of 10 apnoeas per cycle were analysed. Corresponding cyclical variations of cHbD appeared in 98%, cyclical variations of cHbtot appeared in 42% of all apnoeas. During phases of apnoea, a mean decrease of cHbD of -3.45 micromol/l occurred 1.75 seconds after onset of apnoea, and a mean decrease of cHbtot of -0.79 micromol/occurred 0.74 seconds after onset of apnoea. During these apnoeas, the deltaCBV was -44 microl/100 g brain. During phases of ventilation, there was an increase of cHbD and cHbtot to the pre-apnoeic levels. There was a tendency that CytOx values decreased during periodic breathing, the amount of decrease was -0.32 micromol/l. In conclusion, the present study was able to show for the first time that there is cyclical desaturation and reoxygenation of cerebral blood during periodic breathing. Cyclical changes in CBV in association with periodic apnoea occurred only in 42% of apnoea.

Cytomegalovirus associated neonatal pneumonia and Wilson-Mikity syndrome: a causal relationship?

Lung injury caused by intrauterine inflammation has recently been strongly implicated in the pathogenesis of Wilson-Mikity syndrome (WMS). This article supports this theory by suggesting a causative role of intrauterine cytomegalovirus (CMV) infection for the development of WMS. A male premature infant, born at 33 weeks of gestational age, developed chronic lung disease compatible with WMS and diagnostic evaluation was positive for CMV infection. High-resolution computed tomography scan and lung histology revealed typical features of WMS in association with signs of interstitial pneumonia. CMV was found in urine, breastmilk, bronchoalveolar lavage material and lung tissue from open lung biopsy. Follow-up after treatment with ganciclovir and steroids showed resolving lung disease at the age of 6, 10 and 16 months, with lung function signs of mild obstruction. Assuming that a chance coexistence of cytomegalovirus pneumonia and Wilson-Mikity syndrome is rather unlikely, it is possible that intrauterine cytomegalovirus infection caused a pattern of lung injury consistent with Wilson-Mikity syndrome. Further cases of Wilson-Mikity syndrome should be investigated as to a possible role of congenital infection.

[Ureaplasma urealyticum pneumonia and isolation of U. urealyticum from endotracheal tube aspirates of preterm and full-term infants]. / Ureaplasmapneumonien und Nachweis von Ureaplasma urealyticum im Tubussekret bei Früh- und Neugeborenen.

OBJECTIVE: Our purpose was to investigate how many preterm infants with a birth weight 1,250 g with clinical symptoms had Ureaplasma urealyticum in their endotracheal tube aspirates, and how many of them had pneumonia. METHODS: The patients were divided into two groups (group 1: birth weight 1,250 g, n = 45), and these two groups were subdivided into two subgroups (subgroup a: U. urealyticum in aspirate without pneumonia; subgroup b: U. urealyticum in aspirate with pneumonia). RESULTS: In group 1, there were 25 patients. Nine patients (36%) had U. urealyticum in their aspirates, 5 patients (20%) had pneumonia (group 1b), and 4 patients (16%) did not (group 1a). Infants with pneumonia showed a significant increase in parameters of mechanical ventilation, in the duration of mechanical ventilation, and in the duration of oxygen dependence as compared with subgroup 1a. In group 2, there were 45 patients. Six patients of group 2 (13%) had U. urealyticum in their aspirates, 2 patients (4.4%) had a pneumonia (group 2b), and 4 patients (8.8%) did not (group 2b). CONCLUSIONS: In preterm infants as well as in term newborns one should consider U. urealyticum as a potential cause of neonatal pneumonia.

[Kinetic therapy of severe meconium aspiration syndrome]. / Kinetische Therapie bei einem schweren Mekoniumaspirations-Syndrom.

Recent studies showed the possible positive effect of body position changes during mechanical ventilation of severe lung diseases in adult patients. In neonatology kinetic therapy is still rarely used, therefore we present this case report. A full term newborn suffering from severe MAS and peripartal asphyxia was transferred to our NICU to perform extracorporeal lung support, if necessary. After application of a natural porcine surfactant and start of inhalative nitric oxide therapy (10 ppm) a clinical stabilisation was possible. Because of hypercapnia, high frequency oscillation ventilation was introduced later on. The PaCO2 values decreased quickly. A few days later severe pulmonary secretion problems occurred, which led to atelectasis and barotrauma due to local hyperinflation. After several different ventilation strategies had failed to improve the situation, kinetic therapy in combination with conventional mechanical ventilation was started. Under this therapy-concept it was possible to reventilate the atelectatic lung areas, and quickly an improvement of oxygenation was seen. Weaning from the respirator was possible within one week. In conclusion, we think that an important progress in therapy was due to kinetic therapy.

Serial lumbar tapping to prevent posthaemorrhagic hydrocephalus after intracranial haemorrhage in preterm infants.

Posthaemorrhagic ventricular dilation following intraventricular haemorrhage is a serious problem with high morbidity in preterm babies. No consensus exists as to the treatment of intraventricular haemorrhage and as to the treatment or prophylaxis of posthaemorrhagic ventricular dilation. Serial lumbar tapping was already in use to treat existing or being in the offing ventricular dilation. In the present study we evaluated the incidence of posthaemorrhagic hydrocephalus when lumbar tapping was initiated early, i. e. immediately before ventricular dilation had started. Between January 1989 and December 1996 37 preterm infants suffering from intraventricular haemorrhage grade III or grade III plus periventricular haemorrhage were enrolled in this study. Lumbar tapping was started as soon as possible: median (25. percentile-75. percentile) two (0-4) days after onset of haemorrhage. A median of 11 (8-17) punctures was performed in each patient. The outcome was as follows: 6 patients (16.2%) showed complete remission, 24 (64.9%) developed ventriculomegaly and 7 (18.9%) developed posthaemorrhagic hydrocephalus with subsequent need of shunt implantation. With the low incidence of shunt implantations in our study we suggest to reconsider the effectiveness of SLP performed immediately after onset of haemorrhage.

Quantification of cyclical fluctuations in cerebral blood volume in healthy infants.

Cyclical fluctuations in cerebral blood flow velocity in Doppler measurements are a well known phenomenon. In 1992 Livera et al have shown in one patient, that cyclical fluctuations of cerebral blood volume could be measured with near infrared spectroscopy (NIRS). The aim of the present study was a quantification of the amplitude of cyclical fluctuations of cerebral blood volume (represented by total haemoglobin [Hbtot]) in a large number of healthy infants. Furthermore changes of oxygenated haemoglobin (HbO2) and deoxygenated haemoglobin (Hb) were investigated. Measurements were done during two hours of undisturbed daytime sleep. Fifty-eight infants (30 male, 28 female) were included in the study. All but one infant showed cyclical fluctuations. For quantification of cyclical fluctuations only periods during quiet sleep with excellent tracing quality were used. A number of 7894 cycles was analyzed for each of the three NIRS parameters. The median amplitude of the cycling fluctuations was: delta Hbtot 1.1 mumol/l, delta HbO2 1.1 mumol/l, and delta Hb 0.2 mumol/l. The frequency was changing within a range of 3 to 6 cycles/minute. Polynominal regression analysis showed that the relationship of delta HbO2 and delta Hbtot was distinctively stronger compared to the relationship of delta Hb and delta Hbtot. In conclusion we think that these data represent "normal ranges" for parameter fluctuations in long-time NIRS tracings.

High-resolution CT findings in Wilson-Mikity syndrome: a case report.

Wilson-Mikity syndrome (WMS), an uncommon cause of respiratory distress presenting after birth, is radiologically characterised by varying degrees of interstitial thickening and bilateral cyst-like foci of hyperinflation. Aetiology and pathogenesis are still unknown. There are few reports of WMS in the paediatric literature and none describing the features and value of high-resolution CT. The purpose of this report is to describe the radiographic findings and high-resolution CT appearance of WMS and to correlate them with the histopathological findings.