[Prevalence of SARS-CoV-2 in children from a cohort of 2192 patients]. / Prävalenz von SARS-CoV-2 bei Kindern in einer Kohorte von 2192 Patienten.

BACKGROUND: As of 18 June 2020 a total of 187,764 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were reported in Germany and of these 6.9% were under the age of 19 years. There were initial indications that children are often asymptomatic and show a milder clinical course. OBJECTIVE: The aim of this study was to gain information on the prevalence of SARS-CoV­2 infections in a pediatric cohort. MATERIAL AND METHODS: Between 13 March and 18 June 2020 all children from whom a smear for SARS-CoV­2 was taken either to rule out an infection or as a suspected case were included. Data were collected on standardized patient record sheets. The analysis of data was anonymized and retrospective. RESULTS: During the given period 2192 children were investigated and 37 patients tested positive (1.7%) for SARS-CoV­2. Of these 36/37 were suspected cases and 28/37 were symptomatic. The leading symptoms were dry cough, runny nose and fever and three children had to be hospitalized. None showed a difficult course of the disease. Among those tested 505 were patients at risk due to an underlying chronic disease, 3 of whom (0.6%) were tested positive with an asymptomatic or mild course. CONCLUSION: We can confirm the first data showing that children and adolescents often have an asymptomatic or mild clinical course of infection or disease. We found no evidence of a high grey area of SARS-CoV­2 infections in this regional pediatric cohort.

Extrarenal Manifestations in Shigatoxin-associated Haemolytic Uremic Syndrome.

BACKGROUND: Shigatoxin-associated haemolytic uremic syndrome (STEC-HUS) is the most frequent cause of acute kidney injury in children worldwide. Extrarenal manifestations are the main determinants for both, short- and long-term prognosis of patients with STEC-HUS. PATIENTS: 46 patients treated over the last 10 years for STEC-HUS in a single center. METHODS: This retrospective study analysed the incidence and outcome of extrarenal manifestations in our cohort of children with STEC-HUS. Risk factors for extrarenal involvement and adverse outcome were assessed by detailed chart review. RESULTS: Eleven extrarenal manifestations occurred in 9/46 patients comprising 8 neurological, 2 gastro-intestinal, and 1 cardiovascular complication. One patient died from cerebral bleeding. Liver transplantation was required in a girl 18 months after HUS due to secondary sclerosing cholangitis. PATIENTS with extrarenal manifestations were significantly younger and presented with higher leucocyte counts and higher alanine aminotransferase levels at admission. Renal replacement therapy was necessary for a longer period than in patients without extrarenal complications. CONCLUSION: Extrarenal manifestations occurred in about 20% of our patients with STEC-HUS. The identification of risk-factors will help to provide a better management of these patients which might also include novel treatment strategies like complement inhibition.

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 children's 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.

Decrease of the incidence of renin-angiotensin-system inhibitor induced oligohydramnios-sequence in Germany in 2011.

AIM: to assess whether the incidence of angiotensin II-receptor type 1 antagonist (AT1-antagonist)­ or ACE-inhibitor induced cases of oligohydramnios sequence (OHS) in 2011 was reduced after intensive alerts as to the causal association between AT1-antagonist /ACE-inhibitor and OHS in the German medical literature. METHOD: 3 sources of information were used: A nationwide active surveillance of OHS in German paediatric hospitals (ESPED); Embryotox, (Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy) and screening of pubmed (AT1-antagonist/ACE-inhibitor induced OHS). RESULTS: 45 cases of OHS were identified, no case due to maternal AT1-antagonist/ACE-inhibitor treatment. Causes for OHS were: premature rupture of membranes (PPROM) (n = 28), congenital anomalies of fetal kidneys and urinary tract(CAKUT (n = 15), placental insufficiency (n = 1),unknown cause (n = 1). Mortality until discharge was 37.8 % (32.1 % PPROM, 57.1 % CAKUT). Embryotox identified 3 exposures to AT1-antagonists in pregnancy, no case was associated with OHS. The pubmed search did not identify any case of OHS related to AT1-antagonist/ACE-inhibitor in pregnancy in Germany in 2011. CONCLUSION: Treatment of pregnant women with ACE inhibitors or AT1-antagonists still occurs but no cases of AT1-antagonist- or ACE-inhibitor induced OHS were reported in 2011 in Germany most likely due to repeated published alerts underlining the importance of consequent education. OHS remains a serious condition with high mortality despite modern intensive care.

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 children's 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.

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.

Angiotensin II receptor blocker induced fetopathy: 7 cases.

BACKGROUND: During a period of 12 months 7 newborns with a partially severe fetopathy caused most probably by maternal sartan-intake in pregnancy were treated in 5 German teaching hospitals. Sartans antagonize the effect of angiotensin II at the AT1-receptor and are used to treat arterial hypertension. METHOD: We presented 2 cases at the yearly GNPI meeting 2010 and we were informed about similar cases in other German teaching hospitals which we brought together in this publication. RESULTS: In the presented cases, maternal sartan intake was noticed at different times in pregnancy and was in part discontinued some weeks before delivery. In all pregnancies oligohydramnios was present and fetal kidneys displayed a hyperechogenic structure on ultrasound. The newborns' postnatal course varied: oligohydramnios sequence with lung hypoplasia, arterial hypotension and renal insufficiency were the predominant problems of the first days of life. The majority (4/7) of infants did not survive this period, in other cases there was a complete (1/7) recovery of renal function whereas others survived with renal impairment (2/7), in part requiring chronic dialysis. Further distinctive features seen frequently were disturbances of cranial ossification and flaccid paralysis of hands and feet with deviations as well as sensorineural hearing loss. CONCLUSION: These case reports again underline the hazardousness of maternal sartan intake with potential fatal outcome for the newborn. Though the use of sartans in pregnancy is contraindicated and several case reports of sartan induced fetopathies exist, the risk of sartan treatment generally seems to be underestimated.

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.

[Primary ciliary dyskinesia causing neonatal respiratory distress]. / Primäre Ziliendyskinesie als Ursache neonataler Atemnot.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a hereditary disorder of structure and function of the cilia of respiratory epithelium of the upper and lower airways. Prevalence is estimated with 1:15 000 to 1:30 000 births. We present a newborn infant with respiratory distress caused by PCD. PATIENT: On the first day of life, the male newborn developed dyspnoe and cyanosis, so that CPAP and short term ventilation was necessary. Varying atelectasis impressed on the chest radiographs and the diagnosis of PCD was made by nasal brush biopsies. Causative is a lack of the inner dynein arms of the cilia. The clinical features of newborns with the diagnoses of PCD are listed and compared with the own case. CONCLUSION: PCD is a rare cause of neonatal respiratory distress and should be considered in term infants with unknown and prolonged course even if Situs inversus is lacking.

[Pharmacologic and non-pharmacologic pain-therapy in neonatology: synopsis of the current data]. / Medikamentöse und nichtmedikamentöse Schmerztherapie in der Neonatologie: Zusammenstellung der aktuellen Datenlage.

BACKGROUND: There is increasing knowledge about the negative consequences of early pain experiences on the acute and long-term outcome of preterm and term neonates. Despite of it, pain is common in neonatal intensive care. Pharmacologic and nonpharmacologic methods of pain therapy with variable analgesic efficacy exist. METHOD: The aim of this article is to give a compendium of the actual strategies of pain therapies for invasive procedures, endotracheal suctioning, eye-examination and for mechanical ventilation of preterm and term neonates. An evaluation of benefits and drawbacks of the single pain alleviating measures will be done.

Sensitive and convenient method for the quantification of clonidine in serum of pediatric patients using liquid chromatography/tandem mass spectrometry.

An improved and easy to use liquid chromatography/tandem mass spectrometric (LC/MS/MS) method in human serum was developed for the quantification of clonidine (CLD), an alpha2-/alpha1-adrenoceptor agonist, used for analgo-sedation and the therapy of opioid withdrawal in pediatric patients. Sample preparation consisted of precipitation of serum proteins by adding acetonitrile and centrifugation of the sample subsequently. [(2)H4]Clonidine (CLD4) served as internal standard. Chromatographic separation of the supernatant was achieved using a 100mmx3mm, 5microm Thermo Electron BetaBasic C4 column with isocratic flow and elution consisting of 0.1% formic acid/acetonitrile (85/15, v/v) and a flow-rate of 350microl/min resulting in a column pressure of 280-420kPa. LC/MS/MS detection was performed by using a triple-stage quadrupole mass spectrometer (TSQ Quantum, Thermo Electron) working in selected reaction monitoring mode with positive electrospray ionization. The analyte was quantified in a single run within 5min. Linearity was demonstrated over the expected concentration range 0.15-50microg/l CLD. The lower limit of quantification (LLOQ) and the limit of detection were 0.1microg/l and 0.01microg/l, respectively. None of the drugs used concomitantly during analgesic therapy interfered in the assay in vitro. Intra-day precision expressed as RSD was 9.6% or less for CLD, while inter-day result was 10.0% or less for CLD. Intra-day and inter-day accuracy was within +/-4.9% and +/-1.8%, respectively. The method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the US Food and Drugs Administration (FDA). The described method is suitable to analyse serum samples with very small volumes and sets the stage for pharmacokinetic studies in pediatric studies.

Recombinant activated factor seven in acute life-threatening bleeding in neonates: report on three cases and review of literature.

INTRODUCTION: Acute bleeding of different genesis can be a severe, life-threatening problem in neonatology. Recombinant factor seven (rFVIIa) is known to have unique hemostatic properties in adults and older children. CASE PRESENTATION: Three cases of acute life-threatening peri- and postnatal hemorrhage were successfully controlled after the application of fFVIIa. All infants were first treated with vitamin K, fresh-frozen plasma and platelet transfusion. CONCLUSION: The cases substantiate other reports that rFVIIa is an effective treatment for acute, refractory and life-threatening bleeding in neonates and premature infants.

[Intramuscular injections in children]. / Intramuskuläre Injektionen im Kindesalter Notwendiges Ubel oder vermeidbare Körperverletzung?

Intramuscular injections are still part of routine care in the treatment of children. Vaccines, premedications and analgesics are administered by this route. The pain associated with an intramuscular injection is severe, the risk of complications is increased, and pharmacodynamics and pharmacokinetics are unpredictable. In many cases, equivalent alternatives of rectal, oral or intranasal routes of administering pharmacologic agents exist. Intramuscular injection of analgesics and premedications to children are-except in case of emergencies-obsolete. This demand corresponds to the guidelines of the World Health Organization (WHO) and the International Association for the Study of Pain (IASP).

[Does the combination of primary high-frequency oscillation ventilation and prophylactic surfactant therapy improve the prognosis for extremely low birth weight infants?]. / Verbessert die Kombination von primärer Hochfrequenzoszillationsbeatmung und prophylaktischer Surfactantgabe die Prognose extrem kleiner Frühgeborener?

BACKGROUND: Although animal data show a clear advantage of HFOV compared with CMV in the therapy for IRDS, clinical data are still heterogeneous. We have compared our clinical results of HFOV with those of CMV to evaluate the potential benefit. PATIENTS AND METHODS: During the observation period primary care of all extremely low birth weight infants was done in a standardised way with a restricted indication for endotracheal intubation. Intubated patients received surfactant immediately after intubation. Patients requiring an FiO (2) > 0.4 after administration of surfactant received HFOV. RESULTS: 52 patients were included into the study. 21 received CMV and 31 received HFOV. There were no differences between both groups in mortality and morbidity, but patients in the HFOV group were significantly more immature and smaller than those in the CMV group. They also had higher CRIB, SNAP and SNAP-PE scores, thus having a much higher risk of morbidity and mortality. CONCLUSION: In our study babies who were extremely immature and small might have had a profit from the very early administration of surfactant and start of HFOV immediately after endotracheal intubation. Similar results in other small retrospective analyses and also in animal experiments suggest the need for a large randomised controlled trial using early surfactant administration and starting HFOV immediately after intubation.

[Assessment and measurement of pain]. / Messen und Erfassen von Schmerz.

BACKGROUND: The assessment and measurement of pain is essential in the implementation and control of pain relieving strategies. The measurement of pain in infants and children should be based on the consideration of age, cognitive level, psychological status, intercurrent diseases and the social context in order to register the child's individual situation and to avoid misinterpretation. DIAGNOSIS: In the preverbal infant, behavioral and physiological cues have to be interpreted by the caregivers. For the assessment of pain in children of four and older who have at least a basic understanding of the pain concept self assessment methods (as rating scales, specific pain interviews, diaries and questionnaires) can be used. In any case the instruments used should be age appropriate. The instruments used for the different age groups are presented with comments on quality and clinical applicability.