Alveolar recruitment promotes homogeneous surfactant distribution in a piglet model of lung injury.

Uneven distribution of exogenous surfactant contributes to a poor clinical response in animal models of respiratory distress syndrome. Alveolar recruitment at the time of surfactant administration may lead to more homogeneous distribution within the lungs and result in a superior clinical response. To investigate the effects of three different volume recruitment maneuvers on gas exchange, lung function, and homogeneity of surfactant distribution, we studied 35 newborn piglets made surfactant deficient by repeated airway lavage with warm saline. Volume recruitment was achieved by either a temporal increase in tidal volume or an increase in end-expiratory pressure during surfactant administration, yielding an increase in dynamic compliance of the respiratory system of 77% in the first group and an increase in functional residual capacity of 108% in the second group. A third group of piglets (all n = 7) received a combination of both volume recruitment maneuvers, with increases in dynamic compliance of the respiratory system of 100% and in functional residual capacity of 192%. Those animals subjected to increased tidal volume showed an improved surfactant response in terms of oxygenation, ventilation, lung volumes, lung mechanics, and homogeneity of surfactant distribution. Increased end-expiratory volume augmented the surfactant effect only to some extent. The combination of both volume recruitment maneuvers, however, needed lung volumes beyond total lung capacity (approximately 56 mL/kg), thus probably inducing early sequelae of ventilator-induced lung injury. We conclude that volume recruitment by means of increased tidal volumes at the time of surfactant administration leads to a superior surfactant effect owing to more homogeneous surfactant distribution within a collapsed lung.

Frequency, natural course, and outcome of neonatal neutropenia.

OBJECTIVE: We studied the frequency, onset, duration, and prognosis of neutropenia in a neonatal hospital population to define subgroups of neonates who might benefit from cytokine therapy. STUDY DESIGN: The study comprised of 2 parts: in a first retrospective study (I), clinical data of neonates with sepsis (n = 168) were analyzed; in a second retrospective and prospective study (II), clinical data of neonates with neutropenia (n = 131) were studied. In study I, the analysis focused on septic neonates with and without neutropenia, and in study II, on neutropenic neonates with and without primary infection. In the prospective part of study II, granulocyte colony-stimulating factor (G-CSF) plasma concentrations were analyzed in neutropenic neonates (n = 32). RESULTS: Thirty-eight percent of septic neonates were neutropenic. Neutropenia lasted <24 hours in 75% of these patients. It was recorded before or on the day of the clinical onset of sepsis in 87% of patients. The overall incidence of neutropenia was 8.1%. Seventy-two percent of these neutropenic episodes occurred in patients without infection at the time of diagnosis of neutropenia. In the latter patients, the risk of infection secondary to neutropenia was 9%, affecting only premature neonates. Neutropenic episodes without infection were of longer duration and were accompanied by lower G-CSF plasma concentrations than were episodes associated with infection. The percentage of neutropenic episodes primarily associated with infection was higher in VLBW neonates than in term neonates. Likewise, the risk of infection secondary to neutropenia (27%) and the mortality attributable to infection and neutropenia (28%) were significantly higher than in term newborns. CONCLUSION: Considering the priming time for induction of neutrophilia, G-CSF therapy in neonates presenting with severe bacterial infection and neutropenia may be too late. In contrast, neutropenic very low birth weight neonates without primary infection might benefit from prophylactic G-CSF treatment.neonatal sepsis, neutropenia, granulocyte colony-stimulating factor.

Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro.

OBJECTIVES: Besides its vasodilative actions, nitric oxide (NO) is also involved in host defense on a cellular level. We studied the antimicrobial properties of NO in concentrations used with inhaled NO therapy for the treatment of pulmonary hypertension in neonates. DESIGN: In vitro study of bacterial growth of five species, with and without NO exposure. SETTING: Level IV neonatal intensive care unit at a university children's hospital. SUBJECTS: In vitro bacterial cultures. INTERVENTIONS: We tested ten different strains of five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, group B streptococcus [GBS/Streptococcus agalactiae], Escherichia coli, and Pseudomonas aeruginosa), derived from the tracheal isolates of ventilated premature and term infants. Cultures were exposed to three different concentrations of NO (40, 80, and 120 parts per million [ppm]) and bacterial growth was compared with the same strains incubated in ambient air for 24 hrs. After incubation (with or without NO), colony-forming units were counted. MEASUREMENTS AND MAIN RESULTS: Bacterial growth of S. aureus, E. coli, and P. aeruginosa was not reduced with the NO concentrations applied. The number of colony-forming units of S. aureus increased at 80 ppm of NO. Growth of S. epidermidis and GBS was significantly affected at 120 ppm, resulting in decreased numbers of colony-forming units as compared with controls exposed to ambient air. CONCLUSIONS: We conclude that NO has a selective bacteriostatic effect on some of those bacteria most commonly cultured in tracheal specimens of premature infants and neonates. This effect appears to be dose-dependent and occurs in the upper range of dosages used with inhaled NO therapy. However, in the range of dosages applied in ongoing controlled trials of inhaled NO in neonates and premature infants (1 to 80 ppm), a bacteriostatic effect of NO is not to be expected.

Plasma levels and gene expression of granulocyte colony-stimulating factor, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 in neonatal early onset sepsis.

Bacterial sepsis is still a leading cause of neonatal morbidity and mortality. Early onset sepsis in particular, presents with a different clinical course and involves other pathogens than sepsis later in life. In this study, plasma concentrations and mRNA expression of granulocyte colony-stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) of neonates with early onset sepsis were evaluated in cord blood and during the first days of life. Irrespective of prematurity, plasma levels of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8, but not sICAM-1, were excessively elevated in septic neonates when compared with both healthy infants and infants with clinically suspected but not confirmed sepsis. Compared with the corresponding maternal levels, neonatal cytokine cord plasma levels were likewise highly elevated, indicating the endogenous cytokine production by the neonate. With the exception of TNF-alpha, mRNA expression in blood cells from septic infants was, however, not more frequently detectable than in those from nonseptic patients. Cytokine levels decreased significantly within the first days of life, whereas levels of sICAM-1 and C-reactive protein increased during the same time period. In summary, in contrast to C-reactive protein and sICAM-1, cord blood plasma levels, but not the presence of mRNA, of G-CSF, TNF-alpha, IL-1beta, IL-6, and IL-8 can predict neonatal early onset sepsis with a high sensitivity and specificity. Cell types other than blood cells are likely to contribute considerably to the high cytokine production in septic newborns.

Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation.

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was < or =0.14 and a peak inspiratory pressure > or =22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n=8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6%+/-[SD] 11.3% vs 56.2+/-16.4, P=0.05; MEC: 52.6+/-6.3 vs 44.3+/-8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg +/-10.1 mmHg vs 20.0+/-8.2, P < 0.01; MEC: 25.1+/-4.4 vs 22.3+/-5.0, P=0.46) and in dead space (% of tidal volume, LAV: 32.7%+/-10.5% vs 25.9+/-10.1, P < 0.01; MEC: 26.1+/-16.6 vs 18.9+/-10.1, P=0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent.

[Reversal of a right-left shunt and permanent improvement of oxygenation by inhalation of nitrogen monoxide in a premature infant with lung hypoplasia and asphyxia]. / Umkehr eines Rechts-Links-Shunts und dauerhafte Verbesserung der Oxygenierung durch Inhalation von Stickstoffmonoxyd (NO) bei einem Frühgeborenen mit Lungenhypoplasie und Asphyxie.

We report the case of a 29 weeks gestation female premature infant who suffered from severe postnatal asphyxia following spontaneous vaginal delivery. Prenatally lung hypoplasia due to prematurely ruptured membranes with subsequent oligohydramnios was suspected sonographically. Echocardiography revealed right-to-left shunting via PDA and foramen ovale, in addition to that tricuspid incompetence with a pulmonary arterial pressure gradient of 40 mmHg was demonstrated. At an oxygenation index (OI) of 34, an arterio-alveolar oxygen difference (AaDO2) of 639 mmHg, an FiO2 of 1.0 and a maximal paO2 of 37 mmHg during high frequency ventilation (HFV), we applied inhaled nitric oxide (up to 70 ppm) for a duration of approximately 30 hours. Within two hours the inspiratory oxygen concentration could be weaned to an FiO2 of 0.21, mean airway pressures were reduced markedly. Echocardiographically tricuspid incompetence had disappeared, the PDA was closed and now left-to-right shunting across the foramen ovale was demonstrated. The infant was extubated on day 5 and subsequently had oxygen requirements up to an FiO2 of 0.3 during spontaneous breathing for 20 days.

Fatal sepsis caused by Corynebacterium amycolatum in a premature infant.

Corynebacterium amycolatum has not been reported as a cause of human infections up to now, but usually the bacterium is misidentified in clinical specimens as Corynebacterium xerosis. We report the first case of neonatal sepsis due to Corynebacterium amycolatum with a fatal outcome in a premature infant.

Bacterial tracheitis caused by Corynebacterium diphtheriae.

UNLABELLED: Diphtheria has become a rare disease in Germany. We report on an unimmunized 3.5-year-old German girl with a 7-day history of respiratory distress and fever, presenting a clinical picture mimicking typical bacterial tracheitis without pharyngeal and laryngeal manifestation. Diagnosis of diphtheria was not made until culture of tracheal secretions yielded growth of a toxigenic strain of Corynebacterium diphtheriae. The patient died from toxic cardiac failure despite treatment with diphtheria antitoxin. This is the second reported case of isolated bacterial tracheitis caused by Corynebacterium diphtheriae. CONCLUSION: The observation of a lethal course of diphtheric tracheitis emphasizes the paramount importance of immunization against diseases like diphtheria.

Interventional neuropediatrics: treatment of dystonic and spastic muscular hyperactivity with botulinum toxin A.

Therapeutic effect of botulinum toxin A was studied in a group of pediatric patients (n = 28) aged between 6 months and 18 years. The patients were diagnosed with cervical dystonia (n = 6), adductor spasm of the hip (n = 8), spastic drop foot (n = 7) and various other focal motor problems associated with spastic muscular hyperactivity (n = 7). The mean dose of botulinum toxin A (Dysport) used to inject into the affected muscle was 22 U/kg body weight. Reduced muscular hyperactivity with a significant increase in joint mobility was achieved for dystonic (p < 0.0001) as well as for spastic conditions in patients with adductor spasm (p < 0.0002). For these patients the improved joint mobility represented a significant benefit for both daily activities and nursing care. Local paresis and local hematoma were observed in 1/28 and 1/28 patients, respectively; 1/28 patients developed a secondary non-response. However, apart from these side effects, no other adverse reactions to botulinum toxin A treatment were recorded during the treatment and observation period (12-64 months). Our results suggest that botulinum toxin A represents an effective and safe therapeutic substance for the treatment of pediatric patients suffering of focal motor problems due to dystonic or spastic muscular hyperactivity.

Primary treatment of propionic acidemia complicated by acute thiamine deficiency.

Propionic acidemia is often manifested during the neonatal period with vomiting, failure to thrive, lethargy, and hyperammonemic coma when catabolism is prolonged. Mild lactic acidosis frequently accompanies metabolic decompensation. We present two patients with propionic acidemia whose initial manifestation was complicated by severe lactic acidosis caused by thiamine deficiency, which resulted from an inadequate supply of, and an increased need for, thiamine during metabolic stress. To prevent acute thiamine deficiency, we propose early vitamin supplementation during treatment of any severe metabolic decompensation accompanied by insufficient food intake.

Circadian variations of urinary electrolyte concentrations in preterm and term infants.

OBJECTIVES: To determine whether a circadian variation of urinary excretion of calcium and phosphorus exists in preterm infants. STUDY DESIGN: We studied 70 newborn infants (median birth weight 1920 gm, range 660 to 3550 gm; median gestational age 34 weeks, range 25 to 42 weeks) at a median postmenstrual age of 36 weeks (range 32 to 42 weeks). Within a period of 24 hours, four urine specimens were collected during 6-hour periods. The concentrations of calcium, phosphorus, sodium, potassium, and creatinine were determined and creatinine quotients were calculated for each specimen. RESULTS: No clinically relevant circadian variation in urinary excretion for any of these minerals was found. CONCLUSION: If spot urine specimens are used to monitor calcium and phosphorus balance in preterm infants, the time of the day these are collected is not important.

Urinary excretion of adenosine deaminase binding protein in neonates treated with tobramycin.

The potential tubulotoxicity of tobramycin and cefotaxim were assessed in neonates by measuring the urinary level of adenosine deaminase binding protein (ABP) and urinary alpha 1-microglobulin and beta 2-microglobulin. In a prospective study, 33 neonates who received tobramycin and cefotaxim for suspected neonatal sepsis were compared with 48 untreated newborns during the first 10 days of life. The urinary concentrations of ABP and its excretion rates, corrected for body weight and body surface area, were significantly increased from the 1st day of treatment. Urinary alpha 1-microglobulin and beta 2-microglobulin were not elevated under tobramycin and cefotaxim during the first 2 days of treatment. We conclude that ABP may be a sensitive marker for the detection of proximal renal tubular injury during tobramycin and cefotaxim treatments of neonates. The increase in urinary ABP which occurs before an elevation of urinary alpha 1-microglobulin and beta 2-microglobulin may reflect earlier structural than functional alterations. However, since none of the treated infants had signs of electrolyte disorders or glomerular dysfunction, the clinical relevance of ABP measurement should be reevaluated.

von Willebrand factor-collagen binding activity is increased in newborns and infants.

von Willebrand factor (vWF) antigen (vWF:Ag) and vWF-collagen binding activity (vWF:CBA) were measured in plasma by parallel quantitative ELISAs in normal newborns and infants (n = 71). The medians for vWF:Ag (IU/ml) and vWF:CBA (U/ml), respectively, were 1.46 and 1.91 for 2-7 day-old (n = 43), 1.22 and 1.40 for 2-4 week-old (n = 14), 1.22 and 1.15 for 2-6-month-old (n = 14) infants and 0.98 and 1.08 (n = 36) in normal adults. Elevated levels of vWF:Ag, but particularly vWF:CBA were seen for up to 4 weeks of life reaching adult levels between 2 and 6 months of life. The elevated levels of the vWF parameters indicate that caution should be exercised when interpreting laboratory data and diagnosing von Willebrand disease in newborns and young infants and warrant the use of age-specific reference ranges. The efficient haemostasis observed during early neonatal life may in part be due to the increased ability of vWF to interact with collagen.

Low birth weight and nosocomial infection of neonates in a neonatal intensive care unit.

A one year prospective surveillance of nosocomial infections (NI) in a neonatal intensive care unit (NICU) was performed. Among 229 neonates the infection rate was 27.1%, the infection proportion 20.1%, and the incidence density 21.9 infections per 1000 patient days. Infants were stratified into four birth weight categories. Degrees of infection ranged from 44.4% in the < or = 1000 g group to 10.1% in the > 2500 g group. Differences between the groups were statistically significant (P < 0.01). The mean birth weight of infants with NI was significantly lower than that of infants without NI (1711 g, SD +/- 841 g vs. 2213 g, SD +/- 896 g; P < 0.01). Mortality of < or = 1000 g babies was 44.4 and 7.6% in > 2500 g neonates. Major sites of infection were pneumonia (32.3%), blood-stream infections (27.4%), infections of the skin, and surgical site infections (11.3% each). The predominant pathogen was Staphylococcus aureus (24.2%) whilst Gram-negative bacteria accounted for 22.7% of the total. Other major infective agents were Staphylococcus epidermidis, Escherichia coli, and Group B streptococci. It is concluded, that low birth weight was a major risk factor for the acquisition of NI in the observed NICU population.

Zinc deficiency in an exclusively breast-fed preterm infant.

UNLABELLED: A formerly premature, exclusively breast-fed infant with severe zinc deficiency syndrome is presented. He showed the characteristic erosive skin changes, including alopecia, as seen in acrodermatitis enteropathica. In addition, he manifested a failure to thrive and irritability. The diagnosis was confirmed by reduced serum levels of zinc (2.3 mumol/l) and alkaline phosphatase (45 U/l). We consider the reduced zinc supply in the breast milk (5.7 mumol/l) as the most likely cause of the disease. Therapy consisted of oral zinc supplements (50 mumol/kg/day) for a period of 30 weeks. Symptoms and laboratory values normalized completely and did not recur on a normal diet. CONCLUSION: A diet of breast milk can, in rare circumstances, cause insufficient zinc intake resulting in severe zinc deficiency syndrome with characteristic dermatological features. Therapy consists of temporary oral zinc supplementation at a daily dose of 50 mumol/kg.

[Preventive and therapeutic use of intravenous administration of immunoglobulins in intensive care patients in pediatrics]. / Prophylaktischer und therapeutischer Einsatz von intravenös zu verabreichenden Immunoglobulinen bei Intensivpatienten in der Pädiatrie.

The intravenous infusion of immunoglobulin preparations (ivIg) still is no established mode of therapy for neonatal septicemia or for the prevention of nosocomial infections in premature infants. Some recent studies show a decrease in nosocomial infections by ivIg infusions. However, a significant reduction in infections by any specific pathogen has not been demonstrated; the specific antibody content of the ivIg preparations in relation to these pathogens has not been examined. No statistical differences were found regarding duration of hospitalization, morbidity, or mortality of premature infants. ivIg seem to have positive effects on neonatal isoimmune thrombocytopenia or on thrombocytopenia caused by maternal immunothrombocytopenic purpura. There is also evidence that ivIg could have a positive effect on the course of Guillain-Barré syndrome, although this has not been proven for children.