Christoph Hünseler

Early administration of surfactant in spontaneous breathing with nCPAP: feasibility and outcome in extremely premature infants (postmenstrual age ≤27 weeks)

Background:  Spontaneous breathing supported by nasal continuous positive airway pressure (nCPAP) is thought to have some advantages compared with mechanical ventilation in extremely premature infants. In addition, early or prophylactic surfactant administration has been shown to be superior to delayed use. A strategy to combine these two principles was tested in our neonatal intensive care unit (NICU). The aim of this feasibility study was to describe the procedure and compare short‐term results with a historical control.

Early surfactant in spontaneously breathing with nCPAP in ELBW infants--a single centre four year experience.

Objective: To evaluate whether the experience with a method to administer surfactant during spontaneous breathing with nasal continuous positive airway pressure (nCPAP) as primary respiratory support in infants with respiratory distress syndrome (RDS) influences the frequency of its use and affects the outcome of patients.

Continuous Infusion of Clonidine in Ventilated Newborns and Infants: A Randomized Controlled Trial

Objectives: To assess the influence of an infusion of clonidine 1 &mgr;g/kg/hr on fentanyl and midazolam requirement in ventilated newborns and infants. Design: Prospective, double-blind, randomized controlled multicenter trial. Controlled trials.com/ISRCTN77772144. Setting: Twenty-eight level 3 German PICUs/neonatal ICUs. Patients: Ventilated newborns and infants: stratum I (1–28 d), stratum II, (29–120 d), and stratum III (121 d to 2 yr). Interventions: Patients received clonidine 1 &mgr;g/kg/hr or placebo on day 4 after intubation. Fentanyl and midazolam were adjusted to achieve a defined level of analgesia and sedation according to Hartwig score. Measurements and Main Results: Two hundred nineteen infants were randomized; 212 received study medication, 69.7% were ventilated in the postoperative care and 30.3% for other reasons. Primary endpoint: consumption of fentanyl and midazolam in the 72 hours following the onset of study medication (main observation period) in the overall study population. The confirmatory analysis of the overall population showed no difference in the consumption of fentanyl and midazolam. Explorative age-stratified analysis demonstrated that in stratum I (n = 112) the clonidine group had a significantly lower consumption of fentanyl (clonidine: 2.1 ± 1.8 &mgr;g/kg/hr, placebo: 3.2 ± 3.1 &mgr;g/kg/hr; p = 0.032) and midazolam (clonidine: 113.0 ± 100.1 &mgr;g/kg/hr, placebo: 180.2 ± 204.0 &mgr;g/kg/hr; p = 0.030). Strata II (n = 43) and III (n = 46) showed no statistical difference. Sedation and withdrawal-scores were significantly lower in the clonidine group of stratum I (p < 0.001). Frequency of severe adverse events did not differ between groups. Conclusions: Clonidine 1 &mgr;g/kg/hr in ventilated newborns reduced fentanyl and midazolam demand with deeper levels of analgesia and sedation without substantial side effects. This was not demonstrated in older infants, possibly due to lower clonidine serum levels.

Neonatal opiate withdrawal and rooming-in: a retrospective analysis of a single center experience.

AIM To evaluate our treatment of neonatal abstinence syndrome (NAS), our experience with rooming-in of opiate-dependent mothers and to examine the influence of rooming-in on short term outcome of infants exposed to opiates in utero. METHOD Retrospective analysis of maternal and perinatal data of newborn infants with NAS treated between 2004 and 2011 in a level 3 academic childrens hospital in a German metropolis. Therapy of NAS and duration of therapy, length of hospital stay and costs were considered in particular. FINDINGS Data of 77 newborns with NAS were analysed. 84.6% of infants were treated with tincture of opium (79.2% rooming-in, 88.7% no rooming-in). Infants with rooming-in (n=24) had a 17% shorter median duration of therapy [27.0 d (IQR 24.0-38.5), no rooming-in (n=53) 32.5 d (IQR 25.0-54.5)] and shorter median length of hospital stay [33.0 d (IQR 28.0-48.0), no rooming-in 41.5 d (IQR 30.3-54.5)]. Demographic data was comparable between newborns and mothers with or without rooming-in. Costs were median 13 457 € (IQR 8 967-17 494)/patient [rooming-in: 9 547 € (IQR 7 024-16 135), no rooming-in: 14 486 € (IQR 9 479-19 352)]. CONCLUSIONS Rooming-in in NAS should be encouraged to shorten duration of therapy and length of hospital stay and thereby reduce costs. No major problems arose in the care of the infants with NAS when parents stayed with their infants but close monitoring of the newborn and strict instruction of parents are required.

Comparison of sufentanil versus fentanyl in ventilated term neonates.

BACKGROUND Increasingly frequent applications of opioid analgesics in neonatal intensive care require the evaluation of efficacy and side effects. PATIENTS Mechanically ventilated term neonates were consecutively enrolled. METHODS In a double-blind randomized trial 20 newborns received a continuous intravenous infusion of fentanyl (n=10) or sufentanil (n=10) in an assumed equipotent dose of 7:1. The analgesic dose was individually adjusted according to sedation scores. The period between cessation of analgesic medication and successful extubation (weaning time), adverse drug effects and urinary cortisol concentrations were evaluated. RESULTS No significant difference of weaning time was seen between fentanyl and sufentanil group (mean weaning time (+/-SD) of fentanyl group 520+/-381 min, median 380 min; sufentanil group 585+/-531 min, median 405 min, p=0.78, 2-tailed U-Test, Mann and Whitney). The mean opioid dose resulted in a 10:1 ratio (fentanyl 4.11 microg/(kg x h) vs sufentanil 0.41 microg/(kg x h)). We found no marked differences in sedation levels, blood pressure, heart rate, oxygenation index, co-medication or urinary cortisol levels. In both groups similar adverse effects were assessed including respiratory depression, mild withdrawal symptoms or decrease of gastrointestinal motility. CONCLUSION In our study sufentanil did not reduce the weaning period in ventilated term neonates when compared to fentanyl. The equipotent dose ratio for fentanyl/sufentanil was 10:1. According to sedation scores both substances provided effective pain and stress protection.

Observations on the effects of inhaled isoflurane in long-term sedation of critically Ill children using a modified AnaConDa©-system.

Long-term intravenous sedation may present problems due to dependence and side effects. Medical records of children who were administered isoflurane were reviewed. 15 patients (9 boys, 6 girls) with a mean age of 11.8 month (+2.4) were analysed.Analgesia and sedation was given in mean 9.7+1.1 days before commencing inhalation using a modified application device (AnaConDa©). Administration was given over a period of 7.2+1.4 days. Depth of sedation was monitored by using Comfort- and Hartwig-scores. Observations included continuous monitoring of heart-rate, pulse oxymetry, blood pressure and cerebral tissue oxygenation.Within 4 h post administration of isoflurane a satisfactory increase in the depth of sedation was seen and kept till extubation. 6/15 patients received tracheostomies during the observation period. None of the patients observed suffered life-critical events of the modified application of isoflurane proceeded without complications. Ketamine and clonidine infusion rates were significantly reduced (p<0.005) as well as the use and overall infusion rate of midazolam, γ-hydroxy butyrate, fentanyl and morphine (p<0.05).Isoflurane inhalation may provide an additional option for long-term sedation in a specific group of critically ill infants but neurodegenerative toxic effects will have to be taken into account when using volatile anesthetics at any time during infancy.

Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy

Background Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. Objectives We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. Methods We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature. Results We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. Conclusions Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease.

Pain-Related Reactions among Premature Infants with Gestational Age Less than 26 Weeks: An Observational Cohort Study

Introduction: There is insufficient information regarding acute pain reactions among premature infants with a gestational age of less than 26 weeks and no appropriate scale for pain measurement in this age group. We hypothesized that these infants present specific reactions to a standardized pain stimulus within the first 3 days of life. Methodology: Mixed-methods, prospective, open-label, single-arm, observational study. Routine capillary or peripheral blood takes were filmed. The model consisting of a baseline, a preparatory, an interventional and a return-to-baseline phase was filmed. After a pilot evaluation, experienced medical and nursing neonatal intensive care unit (NICU) staff analysed the videos. Results: Twenty infants with gestational ages ranging from 22 weeks and 3 days to 26 weeks (mean 24 weeks) were recruited. Nineteen infants showed pain reactions, with a mean latency of 8.3 s (range 2-30). The majority presented eye movements, changes of the breath pattern and a slight increase in the mean SpO2 value. A high degree of interrater and intrarater reliability was found. Discussion: Premature infants with a gestational age of up to 26 weeks can present a variety of discrete reactions as response to a pain stimulus within the first 72 h of life. Experienced NICU staff can perform a valid and reliable evaluation of these reactions.

Septic shock in children in an urban area in Western Germany--outcome, risk factors for mortality and infection epidemiology.

BACKGROUND Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS Children with septic shock aged 2 months to 17 years. METHODS In a multi-center retrospective study of 20 childrens hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

The flexion withdrawal reflex increases in premature infants at 22–26 weeks of gestation due to changes in spinal cord excitability

Our aim was to study the development of the cutaneous flexion withdrawal reflex among premature infants admitted to the neonatal intensive care unit of the Childrens Hospital, University of Cologne, in 2013.