[Correction of Acidosis in Neonatal Intensive-care Medicine: A National Survey]. / Azidose-Ausgleich in der neonatologischen Intensivmedizin: Eine nationale Umfrage.

BACKGROUND: Metabolic acidosis is a common problem of patients on neonatal intensive care units. Only little data exists in literature and there are no clinical guidelines. The aim of this national survey was to assess criteria for correction of metabolic acidosis in neonatal patients and if there were effects to be observed. METHODS: We designed an online survey and sent it to 304 German children's hospitals. 101 questionnaires were included in our study. RESULTS: The question "How often do you buffer on your ward a week?" was answered 63 times with "zero". In perinatal asphyxia newborns with gestation age over 36+0 weeks 4% of the neonatologists would frequently perform a correction of acidosis, 74.3% would do it rarely and 21.8% never. In syndrome of persistent fetal circulation 28.4% would correct acidosis frequently, 42.0% would correct it rarely and 29.5% would never correct it. In case of sepsis 8.7% would correct acidosis frequently, 70.7% would do it rarely and 20.7% would never correct it. 75.2% of the participants distinguish in buffering a premature or a mature infant. 44.4% of neonatologists saw an improvement of the clinical status of the patient after buffering. 38.3% saw different effects, 16.0% saw no changes and 1.2% saw a worsening of the clinical status. 49.4% of those questioned saw side effects after using sodium bicarbonate as a buffer. CONCLUSION: Correction of acidosis with a buffer is rarely performed on German neonatology wards. The indication of buffering depends on the clinical picture and its underlying problem. Benefits from buffering were seen, as well as side effects.

Managing neonatal severe sepsis in Germany: a preliminary survey of current practices.

BACKGROUND: In 2002 and 2007, the American College of Critical Care Medicine (ACCCM) provided clinical guidelines for hemodynamic support of pediatric and neonatal patients in septic shock. In 2008 and 2013, the Surviving Sepsis Campaign (SSC) Guidelines Committee offered up-to-date clinical guidelines for the management of severe sepsis and septic shock in adults and in pediatric patients. The aim of this study was to assess the standard of care of neonates with severe sepsis and septic shock in German neonatal intensive care units (NICUs) with regard to variability in management and guideline conformity. METHODS: 199 pediatric clinics in Germany were asked to describe their management of septic neonates in a telephone survey. The questionnaire that was used for the preliminary survey was designed based on the ACCCM and SSC clinical guidelines. RESULTS: A total of 90 (45%) surveys were completed and analyzed. Among all hospitals, the guidelines most commonly included in current practice patterns were obtaining cultures before administering antibiotics (100%), determining capillary refill time (99%), and using crystalloids for initial fluid therapy (97%). The guidelines least commonly included in current practice were determination of ammoniac to rule out inborn errors of metabolism (51%) and the use of dopamine as the first choice of hemodynamic support (48%). CONCLUSIONS: The management of sepsis, severe sepsis, and septic shock in neonates is not always guideline consistent, but quite a number of ACCCM and SSC guidelines were included in the current practice pattern.

Flow behavior of fetal, neonatal and adult RBCs in narrow (3-6 µm) capillaries--Calculation and experimental application.

BACKGROUND AND OBJECTIVES: In capillaries with diameters less than those of resting RBCs, the cells have to deform to pass through such narrow vessels. Since RBCs of fetuses, neonates and adults differ in their geometrical properties the flow behavior of RBCs with different sizes in uniform tubes with diameters of 3 to 6 µm were studied by means of a micropipette system and a mathematical model. Assumptions in this model include an RBC flow velocity of 1 mm/s, axisymmetric cell shape and a gap between the RBC and the vessel wall that allows sufficient lubrication. The flow resistance depends on the surface area and volume of RBCs, the plasma viscosity and the vessel diameter. METHODS: Surface area and volume of different RBC populations (20 fetuses, 20 preterm neonates, 10 term neonates and 10 adults) were determined by means of a micropipette system and plasma viscosity was measured using a capillary tube viscometer. The flow behavior of RBCs with different volumes (61, 83 and 127 fl) was studied by direct microscopic observation using a micropipette system. The micropipettes had diameters of 3.5, 4.1, 5.1, and 6.0 µm. The flow velocity of the RBC in the pipettes was 1 mm/s and the calculated and measured cell lengths were compared. RESULTS: Volume and surface area of RBCs were 140 ± 29 fl and 172 ± 20 µm2, respectively, in the fetuses, decreased with increasing maturity (term neonates: 110 ± 20 fl and 149 ± 18 µm2) and reached the lowest values in adults (93 ± 14 fl and 136 ± 12 µm2). Plasma viscosities increased with increasing maturity due to rising plasma protein concentrations. The flow model leads to the following conclusions: During the passage of 3- to 6-µm vessels, the large fetal and neonatal RBCs are more elongated than the smaller adult RBCs. The critical vessel diameter, i.e., when the rear of the RBC becomes convex during passage of a narrow capillary, was 4.1 µm for fetal RBCs, 3.6 µm for neonatal RBCs and 3.3 µm adult cells. Suspended in the same medium, fetal and neonatal RBCs require 27% (term neonates) to 100% (fetuses) higher driving pressures than adult RBCs to achieve the necessary elongation for passing through a 4.5-µm capillary. However, the different RBCs require similar driving pressures if the cells are suspended in the corresponding autologous plasma. Cell lengths of the RBCs with different geometry determined during the flow experiments agreed with the predicted values. CONCLUSION: We conclude that the large size of fetal and neonatal RBCs may cause impaired flow in narrow vessels with diameters below the critical values of 3.6 to 4.1 µm. In vessels with diameters above the critical diameter (Dcr), the disadvantage of the large size of neonatal and fetal RBCs appears to be completely compensated for by the lower plasma viscosity.

Treatment of neonatal abstinence syndrome in preterm and term infants.

OBJECTIVE: Neonatal abstinence syndrome (NAS) is treated with a variety of drug preparations. With the optional treatment of NAS with chloral hydrate, phenobarbital or morphine the cumulative drug consumption of the mentioned drugs, the length of hospital stay and treatment duration was evaluated in preterm and term neonates. METHODS: Retrospective, uncontrolled study which evaluates different therapies of neonatal abstinence syndrome (NAS) in preterm and term neonates. RESULTS: During the past 16 years data were obtained from medical records of 51 neonates with NAS; 9 preterm and 35 term neonates were evaluated and 7 were excluded because of incomplete data sets. 31 (72.1%) received a pharmacological treatment (6 preterm and 25 term neonates). Treatment started at 4.3 [3.3-5.3] d. Mean duration of treatment was 11.7 [6.6-16.7] d. In our study chloral hydrate (ch) and phenobarbital (pb) were first line medication escalated by the morphine (mp) solution. Mean cumulative dosage of ch was 643.5 [260.3-1 026.7] mg, of pb 53.2 [19.7-86.8] mg and of mp 4.22 [0-8.99] mg. CONCLUSION: Our study group showed similar treatment duration and length of hospital stay compared to other studies. The cumulative dose of mp was lower compared to most studies. This benefit resulted at the expense of a further medication with pb and ch. However, 6 of 9 preterm neonates needed significantly less pharmacological therapy compared to term neonates indicating less susceptibility of immature brain to abstinence of maternalo-pioids.

Partnerships between Medical Centres and General Hospitals Providing Normal Care Standards in Gynaecology and Obstetrics in Germany.

Hospital managers and the heads of medical departments are nowadays being faced with ever increasing demands. It is becoming difficult for some small hospitals to find highly experienced or even experienced medical staff, to provide specific health-care services at break-even prices and to maintain their position in competition with other hospitals. On the other hand, large hospitals are facing enormous pressure in the investment and costs fields. Cooperation could provide a solution for these problems. For an optimal strategic exploitation of the hospitals, their direction could be placed in the hands of a joint medical director. However, the directorship of two hospitals is associated both with opportunities and with risks. The present article illustrates the widely differing aspects of the cooperation between a medical centre and a general hospital providing standard care from both a theoretical point of view and on the basis of practical experience with an actual cooperation of this type in Heidelberg.

Stable precursor fragments of vasoactive peptides in umbilical cord blood of term and preterm infants.

BACKGROUND: Though various neurohormonal systems are concurrently activated during birth, their biological effectors are not always easy to measure due to their short half-life in vivo, instability in biological samples, or very low concentrations. METHODS: Using a recently discovered chemiluminescence assay, we measured the stable precursor fragments mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1) and C-terminal pro-vasopressin (CT-proAVP or copeptin) immediately after birth in umbilical venous cord blood from 119 infants with a gestational age of 23-42 weeks and evaluated their possible functions. RESULTS: Cord blood levels of MR-proANP, MR- proADM, CT-proET-1, and CT-proAVP were considerably higher compared with normal adult levels. The CT-proAVP concentrations were 10-fold higher in term, and 70-fold higher in extremely preterm infants. MR-proANP showed 4-fold higher levels in term infants and 20-fold higher levels in extremely preterm infants. Levels of MR-proADM and CT-proET-1 were 2- to 3-fold higher in preterm and term infants. All four parameters showed significantly decreased values with increasing gestational age and a significant correlation between CT-proET-1 and MR-proADM. CONCLUSION: Our results indicate that vasoactive and natriuretic mediators play a functionally relevant role in circulatory transition from fetal to neonatal life.

Respiratory distress syndrome due to a novel homozygous ABCA3 mutation in a term neonate.

The authors report, for the first time in the literature, a case of respiratory distress syndrome in a term baby due to homozygosity for a p.Trp308Arg/W308R substitution in the ATP-binding cassette transporter 3. The sequence was confirmed by genetic analysis of the baby and both parents. Management and long-term outcome of a patient carrying this novel genetic defect have not been reported in the literature before. Currently, lung transplant appears to be the only long-term survival option available, for which, our patient is being evaluated.

Lipid A decreases human erythrocytes deformability by increasing intracellular Ca(2+): effects of verapamil, staurosporine and the rho-kinase inhibitor Y-27632.

There are several reports demonstrating an involvement of bacterial toxins in the rigidity of red blood cells (RBC). The present study investigates the influence of E. coli F-583-Rd lipid A on RBC deformability under mechanical shear stress. Verapamil (Ca(2+) channel inhibitor), staurosporine (protein kinase inhibitor) and Y-27632 (rho-kinase inhibitor) were used to modify the effect of lipid A on RBC deformability. We also determined if E. coli F-583-Rd Lipid A could induce an increase of intracellular Ca(2+) concentration. For the deformation measurements RBC (10 adult donors) were incubated with E. coli F-583-Rd lipid A (100 µg/ml) and also co-incubated with either verapamil (10(-7) mol/l), staurosporine (10(-7) mol/l) or Y-27632 (10(-7) mol/l). The deformation of the RBC under different shear stresses (0.6-60 Pa) was measured by a shear stress diffractometer (Rheodyne SSD). Intracellular Ca(2+) was determinded by flow cytometry in RBC incubated with Lipid A and labeled with fluorescent Fluo-4/AM which binds intracellular Ca(2+) with high affinity resulting in enhanced green fluorescence intensity. At increasing shear stresses Lipid A induced a significantly lower elongation. Co-incubation of the erythrocytes with verapamil or staurosporine inhibited lipid A induced decrease in elongation while Y-27632 had no effect. Verapamil, Staurosporine and Y-27632 did not influence the elongation response of the cells under control conditions. Lipid A induced a marked increase in fluorescence Fluo-4/AM indicating increased intracellular Ca(2+). These results suggest that E. coli F-583-Rd lipid A is able to influence red blood cell rigidity by a rapid and significant increase of intracellular Ca(2+) concentration. Verapamil and staurosporine abolished the decrease in deformability of Lipid A incubated RBC.

[Developmental screening of preterms at an early stage postpartum]. / Frühzeitiges entwicklungsneurologisches Screening frühgeborener Kinder von Geburt an.

Preterm infants are at high risk to develop neurological disorders. Therefore extensive follow-up programs with a combination of various instruments are needed for early detection of infants with major or minor developmental disorders and behavioral problems. The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) is based on standardized observation protocols and provides a powerful method to assess behavior and brain development directly after birth, so can be used as an early screening instrument.

Respiratory Deleted in Malignant Brain Tumours 1 (DMBT1) levels increase during lung maturation and infection.

Deleted in Malignant Brain Tumours 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds and aggregates various bacteria and viruses in vitro. Studies in adults have shown that DMBT1 is expressed mainly by mucosal epithelia and glands, in particular within the respiratory tract, and plays a role in innate immune defence. We hypothesized that respiratory DMBT1 levels may be influenced by various developmental and clinical factors such as maturity, age and bacterial infection. DMBT1 levels were studied in 205 tracheal aspirate samples of 82 ventilated preterm and full-term infants by enzyme-linked immunosorbent assay. Possible effects of various clinical parameters were tested by multiple regression analysis. DMBT1 levels increased significantly with lung maturity (P < 0.0001 for both gestational and postnatal age) and in small-for-gestational-age infants (P = 0.0179). An increase of respiratory DMBT1 levels was detected in neonatal infections (P < 0.0001). These results were supported by Western blotting. Immunohistochemical analyses of archived newborn lung sections (n = 17) demonstrated high concentrations of DMBT1 in lungs of neonates with bacterial infections. Our data show that preterm infants are able to up-regulate DMBT1 in infection as an unspecific immune reaction.

Effect of activators and the phosphodiesterase inhibitors pentoxifylline and enoximone on the deformability of neutrophils in neonates and adults.

BACKGROUND: Stimulated polymorphonuclear leukocytes (PMN) are extremely rigid compared to resting PMN. They may obstruct narrow vessels and contribute to ischaemic organ injury. Deformability is a prerequisite for both active and passive movement in the microcirculation. AIM: The investigation was designed to study whether stimulators and inhibitors of stimulation show different effects on deformability of neonatal and adult PMN. METHODS: Deformability of PMN was assessed by complete aspiration of a PMN into a micropipette with an internal diameter of 5 microm. Blood samples from 20 neonates and 20 adults were studied before and after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), interleukin-8 (IL-8) or tumour necrosis factor-alpha (TNF-alpha). Moreover, effects of the phosphodiesterase inhibitors Pentoxifylline (PTX) and Enoximone on the deformability of stimulated PMN were investigated. RESULTS: fMLP, IL-8 and TNF-alpha significantly delayed aspiration times of PMN in relation to the concentrations of the stimulators. The addition of PTX or Enoximone to stimulated PMN increased the deformability up to 60% depending on the concentration of the inhibitors. No significant differences in the aspiration times were found between neonatal and adult PMN at any of the experimental conditions after activation with the three stimulators and treatment with the two inhibitors. CONCLUSION: Neonatal and adult PMN show similar reduction of passive deformability when stimulated with either fMLP, IL-8 or TNF-alpha compared to resting PMN and a similar improvement of deformability in response to PTX or Enoximone.

Effects of intralipid infusion on blood viscosity and other haemorheological parameters in neonates and children.

AIM: To study acute haemorheological effects of intralipid in preterm and full-term neonates and children. Circulatory complications of intralipid infusion, such as increases in pulmonary and peripheral flow resistance, have been associated with impaired blood rheology. METHODS: During total parenteral nutrition, 10 preterm infants, 10 full-term neonates and 10 children received an initial dose of intralipid as continuous infusion (0.6 g/kg) over 4 h. Additionally, blood of 10 healthy preterm infants, 10 full-term neonates and 10 adults was incubated with intralipid. Whole blood and plasma viscosity (capillary viscometer), red blood cell (RBC) deformability (rheoscope) and RBC aggregation (Myrenne aggregometer) were measured before and after intralipid infusion and before and after in vitro incubation of blood with intralipid. RESULTS: During intralipid infusion, plasma triglyceride levels increased from 0.13 +/- 0.27 to 2.16 +/- 0.68 g/l in the preterm infants, from 0.14 +/- 0.21 to 1.64 +/- 0.54 g/l in the full-term neonates and from 0.65 +/- 0.31 to 2.26 +/- 0.60 g/l in the children. Whole blood viscosity decreased by about 10% after intralipid in all three groups due to similar decreases in haematocrit. RBC aggregation decreased by about 20% after intralipid infusion. Plasma proteins, plasma viscosity and RBC deformation were not affected by intralipid. In vitro incubation of blood with intralipid resulted in a marked reduction of RBC aggregation that was related to the intralipid concentration. At intralipid concentrations of 4 and 8 mg/ml, no RBC aggregation was noted in preterm and full-term neonates. In adults, RBC aggregation decreased by 50%. CONCLUSIONS: Previously described deleterious effects of intralipid on circulation can not be explained by changes in haemorheological properties.

Restrictive dermopathy: case report, subject review with Kaplan-Meier analysis, and differential diagnosis of the lethal congenital contractural syndromes.

We report on a 34-week-old infant with restrictive dermopathy (RD), a rare lethal genodermatosis, characterized by an abnormal skin growth and differentiation with thin, tightly adherent skin that causes a dysmorphic face, generalized flexion joint contractures, and respiratory insufficiency. Kaplan-Meier analysis of 32 previously well-described infants affected with RD showed a median survival of 132 hours. Lethal congenital contractural syndromes, including Pena-Shokeir phenotype, cerebro-oculo facio-skeletal syndrome, and lethal multiple pterygium syndrome, should be considered first in the differential diagnosis. Other lethal contractural syndromes are discussed.