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OA Förderung 2022 Background: Infections, major surgeries, and hyperinflammatory syndromes are known to trigger Systemic Inflammatory Response Syndrome (SIRS). Discrimination between infectious and noninfectious inflammation often poses a challenge in chronically ill patients with multiple comorbidities. These patients are routinely treated with a variety of anti-infective medications before a pathogen is iden- tified. With the goal of improving pathogen detection rates and interventions, we evaluated Next Generation Sequencing (NGS) as a highly sensitive and fast means of detecting free microbial DNA in a small amount of serum samples from children with ongoing SIRS. Methods: We describe seven complex pediatric patients of SIRS or prolonged fever (>38.5 °C) >72 hours in which serum samples ana- lyzed by NGS had a major impact on therapy. One patient was analyzed twice. Results: In eight NGS there were six positive results (two bacterial, three viral, one fungal) which were subsequently confirmed by microbiological culture or polymerase chain reaction (PCR) in five of the six NGS. In five of the eight performed NGS, results led to a change of therapy: antibiotic therapy was discontinued in two, escalated in one, an initiated in another; in one an antiviral was administered. Conclusions: NGS may become a valuable addition to infectious disease diagnostics in cases of pediatric SIRS. However, NGS has not yet been validated as a diagnostic method in pediatric as a diagnostic method in pediatric patients and results should therefore be interpreted with caution. Multi-center NGS evaluation studies are currently being planned.

Introduction In pediatric patients, flexible bronchoscopy requires deep sedation. Different sedation regimes are common, but only some of them include opioids. Due to their antitussive effect, the use of short-acting opioids may be beneficial for this particular indication, but additional respiratory depression may lead to an increase in adverse events. Here, we systematically compared sedation regimes in children undergoing flexible bronchoscopy with either propofol alone, or a combination of propofol and remifentanil. The primary outcome parameter was the frequency of coughing episodes during the intervention. Secondary outcome parameters were frequency and types of complications, patient satisfaction, examiner satisfaction, and recovery time after finishing the sedation. Methods Fifty children aged 1-17 years undergoing flexible bronchoscopy under deep sedation with propofol were randomly assigned to two groups: PR receiving propofol and remifentanil and PP receiving propofol only. Sedation depth was predefined as Comfort Score 10-13. Results We found significantly less coughing episodes ([med (IQR)] PR: 0.73 (0.28-2.45)/min; PP: 1.98 (1.26-3.12)/min; p = .010) and shorter recovery time in Group PR (PR: 13.5 (8-17.5) min; PP: 21.0 (14-27) min; p = .011). Examiner's satisfaction was higher in Group PR (PR: 10 (8-10); PP: 9 (7-9); p = .012). The number of adverse events, patient satisfaction, and required propofol dose during the intervention did not differ between groups. Conclusion We suggest the combination of propofol with remifentanil instead of using propofol alone in pediatric procedural sedation for flexible bronchoscopy.

SummaryBackground In pediatric patients, invasive procedures such as the insertion of a central venous catheter or gastroscopy require deep sedation. It is unknown whether listening to parental voice during deep sedation in children can reduce sedative doses. Aim The aim of this prospective study was to determine the effect of listening to a parent's voice during deep sedation on consumption of sedatives in children. Methods Fifty children aged 2–14 years undergoing central line placement or gastroscopy under deep sedation with propofol were randomly assigned to two groups: (A) listening or (B) not listening their parents’ recorded voice reading a standardized text by the use of earphones. Depth of sedation was monitored by Comfort Score and by Bispectral Index. Results Mean sedative dose of propofol in both groups was equal (A 0.25 mg·kg−1·min−1; B 0.28 mg·kg−1·min−1; Δ −0.03 mg·kg−1·min−1 (CI 95% −0.08 to 0.01); P = 0.089). Furthermore, complication rate (P = 1.0) and recovery time (A 14.5 min; B 16.1 min; Δ = −1.6 min (CI 95% −6.98 to 3.81); P = 0.60) did not differ between the intervention and the control group. Conclusion Listening to parental voice during deep sedation does not result in a reduction of sedative dose in children undergoing short medical procedures.

Granulocyte transfusions for neutropenic patients have been used for over 40 years, although effectiveness, indications, and both patient and donor safety remain debated. This single-center study assessed the side effects, clinical course, and survival of granulocyte transfusions in critically ill pediatric patients, with underlying hemato-oncological disorders, prolonged neutropenia, and proven or suspected severe infection. Donor-specific side effects and influence of donor-specific characteristics on patient outcome were also investigated. A median of 4.02 × 10(10) cells was collected from 39 healthy donors for 118 granulocyte concentrates. Donors reported no significant side effects. Complications for patients were frequent but mostly minor and included vomiting, hypotension, and dyspnea. In one episode of life-threatening dyspnea, association with the granulocyte transfusion could not be ruled out. Overall survival on day 100 was 61.9 %. Patients received a median of 0.13 × 10(10) cells per kg body weight. Doses above this median were associated with a significantly better survival. Lower patient weight and age-/sex-adjusted weight were also associated with better survival.Granulocyte mobilization and collection is a safe practice. Transfusions are well tolerated in critically ill patients. Patient weight and transfused cells per kg bodyweight are major determinants of survival in pediatric patients.• Granulocyte transfusions for neutropenic patients have been used for over 40 years • The effectiveness of the technique remains controversial • Patient and donor safety remain debated • New mobilization protocols generate higher yields of granulocytes What is new: • Granulocyte collection can safely be performed • Granulocytes can safely be administered to patients • Lower patient weight and age-/sex-adjusted weight are associated with better survival rates • Patients receiving above 0.13 × 10 (10) cells per kg body weight had an excellent outcome • Further standardized, prospective studies are warranted.

In general anesthesia, cartoon watching and playing video games reduce anxiety in children. It is unknown whether watching a video in the intervention room has a similar effect, and therefore is able to reduce sedative doses in children undergoing small medical procedures. Aim of this prospective study was to determine the effect of watching a standardized cartoon immediately before and during sleep induction for deep sedation on consumption of propofol in children.50 children aged 2-14 years undergoing deep sedation were randomly assigned to 2 groups: (A) watching or (B) not watching a standardized videoclip during sleep induction with propofol. The achievement of predefined sedation depth was objectified by measuring Comfort Score (aim 10-14) and Bispectral Index (aim 50-60).The median sleep induction dose of propofol did not differ in both groups (A: 1.76 (0.62-4.37) mg/kg; B: 1.37 (0.66-5.26) mg/kgKG; p=0.65). Cartoon watching was associated with shorter sleep onset latency (A: 120 (60-480)s; B: 240 (40-600)s; p=0.043). Subgroup analysis reveals this especially for school children and girls. In both groups no complications occurred.Children watching a standard cartoon during sleep induction for deep sedation have a shorter sleep onset time but sedative dose is not reduced.Vor und während der Einleitung einer Vollnarkose reduziert das Ansehen eines Cartoons oder das Spielen von Videospielen bei Kindern Angst. Es ist nicht bekannt, ob das auch im Zusammenhang mit Sedierungen gilt und die notwendige Sedativadosis für kleine Eingriffe oder Prozeduren bei Kindern durch das Ansehen eines Films reduziert werden kann. Ziel dieser prospektiven Studie war es deswegen, den Effekt zu ermitteln, den das Ansehen eines standardisierten Videos unmittelbar vor und während Schlafinduktion für eine tiefe Sedierung auf den Propofolbedarf bei Kindern hat.50 Kinder zwischen 2 und 14 Jahren wurden in 2 Gruppen randomisiert, denen während medikamentöser Induktion mit Propofol für eine tiefe Sedierung entweder ein Standardfilm (Gruppe A) oder kein Film (Gruppe B) präsentiert wurde. Die gewünschte Schlaftiefe war definiert und wurde durch Erheben eines klinischen Scores (Comfort Score, Ziel 10–14) und den Einsatz von Bispektralem Index (Ziel 50–60) objektiviert.Die mediane Schlafinduktionsdosis für Propofol unterschied sich in beiden Gruppen nicht (A: 1,76 (0,62–4,37) mg/kg; B: 1,37 (0,66–5,26) mg/kgKG; p=0,65). Die Kinder, die einen Cartoon sahen, hatten eine kürzere Einschlafzeit (A: 120 (60–480)s; B: 240 (40–600)s; p=0,043). In der Subgruppenanalyse zeigt sich, dass dies insbesondere für Mädchen und Schulkinder gilt. In beiden Gruppen kam es zu keinerlei Komplikationen.Kinder, die während Sedierungseinleitung einen Film ansehen, haben eine kürzere Einschlafzeit, die Dosis der notwendigen Sedativa ist jedoch unbeeinflusst.

Introduction and aim. Procalcitonin is widely used as a biomarker to distinguish bacterial infections from other etiologies of systemic inflammation. Little is known about its value in acute liver injury resulting from intoxication with paracetamol.Material and methods. We performed a single-center retrospective analysis of the procalcitonin level, liver synthesis, liver cell damage and renal function of patients admitted with paracetamol-induced liver injury to a tertiary care children’s hospital. Children with acute liver failure due to other reasons without a bacterial or fungal infection served as the control group. Twelve patients with acute paracetamol intoxication and acute liver injury were compared with 29 patients with acute liver failure.Results. The procalcitonin levels were higher in children with paracetamol intoxication than in patients with acute liver failure without paracetamol intoxication (median 24.8 (0.01-55.57) ng/mL vs. 1.36 (0.1-44.18) ng/mL; p < 0.005), although their liver and kidney functions were better and the liver cell injury was similar in both groups. Outcome analysis showed a trend towards better survival without transplantation in patients with paracetamol intoxication (10/12 vs. 15/29). Within each group, procalcitonin was significantly correlated with alanine aminotransferase and aspartate aminotransferase but was not correlated with the International Normalized Ratio or paracetamol blood levels in the paracetamol group. In conclusion, paracetamol intoxication leads to a marked increase in procalcitonin serum levels, which are significantly higher than those seen in acute liver failure.Conclusion. The underlying mechanism is neither caused by infection nor fully explained by liver cell death alone and remains to be determined.

The use of Propofol and Remifentanil for analgosedation in children is common and safe. For sedation monitoring clinical scores as Comfort Score (CS) as well as bispectral index (BIS) are frequently applied. The impact of BIS for sedation monitoring in pediatric patients is still under debate. This prospective study aims to investigate whether dual sedation monitoring of CS and BIS compared with monitoring of CS alone during muscle biopsies in children can reduce sedative doses, reduce awakening time and prevent complications.50 pediatric patients requiring sedation for open muscle biopsy were prospectively enrolled. Analgosedation was performed with remifentanil and propofol. Patients were randomly assigned to 2 groups: In 25 patients, sedation was monitored using CS alone, and in 25 patients CS and BIS monitoring were simultaneously applied. The primary outcome was the propofol dose applied during muscle biopsy. Secondary outcome parameters were recovery time and the frequency of complications.The median CS during the intervention in both groups was equal (11, P=1.000). The median BIS in group 2 was 59. No complications occurred in either group. There was no difference in propofol dose in either group (8.4 vs. 7.2 mg/kg/h; P=0.58) and no difference in the duration until eye opening (9 vs. 11 min; P=0.081).For children undergoing minor surgical procedures under analgosedation, BIS monitoring does not affect the sedative dose, the time until eye opening or the frequency of complications.Zur Analgosedierung von Kindern hat sich eine Medikamentenkombination aus Propofol und Remifentanil bewährt. Zum Sedierungsmonitoring sind sowohl klinische Scores wie der Comfort Score (CS) als auch der bispektrale Index (BIS) üblich. Die Bedeutung von BIS zum Sedierungsmonitoring bei Kindern ist nach wie vor nicht eindeutig und Gegenstand wissenschaftlicher Diskussionen. Ziel der vorliegenden prospektiven Studie ist es zu untersuchen, ob bei pädiatrischen Patienten das kombinierte Sedierungsmonitoring mit CS und BIS verglichen mit einem alleinigen Monitoring mittels CS während offener Muskelbiopsien zu einer Reduktion der Sedativadosis, einer verkürzten Aufwachzeit und einer Reduktion der Häufigkeit von Komplikationen führt.50 pädiatrische Patienten, die während offener Muskelbiopsien Propofol und Remifentanil zur Analgosedierung erhielten, wurden untersucht und dazu in 2 Gruppen randomisiert: Bei 25 Patienten wurde die Analgosedierung mittels CS allein, bei 25 mittels CS und zusätzlichem BIS Monitoring überwacht. Primärer Outcome Parameter war die benötigte Propofoldosis während des Eingriffs. Sekundäre outcome parameter waren Aufwachzeit und Häufigkeit von Komplikationen.Der mediane CS während des Eingriffs war in beiden Gruppen gleich (11, P=1,000). Der mediane BIS in Gruppe 2 war 59. In beiden Gruppen kam es zu keinerlei Komplikationen. Es gab keinen Unterschied in der applizierten Propofoldosis (8,4 vs. 7,2 mg/kg/h; P=0,081) und in der Aufwachzeit zwischen beiden Gruppen (9 vs. 11 min; P=0,081).Für die Analgosedierung während kleiner chirurgischer Eingriffe bei pädiatrischen Patienten hat das zusätzliche Sedierungsmonitoring mittels BIS keinen Einfluss auf die verwendete Sedativadosis, die Aufwachzeit oder die Häufigkeit von Komplikationen.

Bacillus cereus is a spore-forming, gram-positive bacterium that causes food poisoning presenting with either emesis or diarrhea. Diarrhea is caused by proteinaceous enterotoxin complexes, mainly hemolysin BL, non-hemolytic enterotoxin (NHE), and cytotoxin K. In contrast, emesis is caused by the ingestion of the depsipeptide toxin cereulide, which is produced in B. cereus contaminated food, particularly in pasta or rice. In general, the illness is mild and self-limiting. However, due to cereulide intoxication, nine severe cases with rhabdomyolysis and/or liver failure, five of them lethal, are reported in literature. Here we report the first case of life-threatening liver failure and severe rhabdomyolysis in this context that could not be survived without emergency hepatectomy and consecutive liver transplantation.

This study reports the first cases of neurogenic stunned myocardium in two children with vein of Galen aneurysmal malformation after interventional treatment. Two newborns with vein of Galen aneurysmal malformation and high output cardiac failure developed a severe reversible left ventricular dysfunction shortly after embolization, concurrently with acute hydrocephalus. There was a resolution of the cardiac symptoms of left ventricular dysfunction within a few days under treatment with milrinone and dobutamine. Reversible left ventricular dysfunction is observed in adult patients mainly after subarachnoid hemorrhage and is called neurogenic stunned myocardium (NSM). Other forms of brain injuries have also been identified accounting for this condition in adults. In pediatric population especially with specific cerebral diseases, NSM may be underdiagnosed.

Background There is only sparse data on the use of non-invasive ventilation (NIV) in acute respiratory failure (ARF) in infants and children. For this setting we investigated feasibility and efficacy of NIV and aimed to identify early predictors for treatment failure. Patients and Methods Retrospective chart review was performed for all patients treated with NIV for ARF from 2003 to 2010 on an 8-bed pediatric intensive care unit of a tertiary university hospital. Results Seventy-four patients were treated with NIV. One patient did not tolerate mask ventilation and needed immediate invasive ventilation. Intubation rate of the remaining patients was 23% and mortality 15%. Institution of NIV led to significant improvement of both respiratory and heart rate in all patients within the first hour and to further stabilization within the next 8–10 hr. In patients with NIV success blood gases improved significantly 1–2 hr after starting NIV. Multivariate analysis identified low pH after 1–2 hr to be an individual risk factor for NIV failure. Other factors tested were age, underlying disease, acute respiratory insufficiency versus post-extubation failure (PEF), and 1–2 hr after starting NIV oxygen saturation, respiratory rate, PCO2, and FiO2. Patients with PEF tended to show better outcomes compared to those with acute respiratory insufficiency. Conclusion NIV can be effective in infants and children with ARF. Low pH 1–2 hr after start of NIV is associated with NIV failure. It may therefore be useful in the decision to continue or stop mask ventilation. Pediatr. Pulmonol. 2011; 46:1114–1120. © 2011 Wiley Periodicals, Inc.

Background Antimicrobially pre-treated children with systemic inflammation often pose a diagnostic challenge to the physician. We aimed to evaluate the additional use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative pathogens in children with suspected systemic bacterial or fungal infection. Methods Prospective observational study in 39 children with systemic inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary outcome was the rate of positive blood cultures (BC), compared to the rate of positive SeptiFast (SF) results. Results In total, 14 SF-samples yielded positive results, compared to 4 positive BC (p

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.Children with septic shock aged 2 months to 17 years.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.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% (p0.01 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% (p0.05 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.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.

SummaryBackground Open muscle biopsies in children are generally performed under general anesthesia. Alternatively, deep sedation and analgesia may be required. Objectives The aim of our study was to compare the Bispectral Index (BIS) and Comfort Score (CS) with respect to their clinical significance for sedation/analgesia in children undergoing open muscle biopsy. Methods Thirty pediatric patients subjected to open muscle biopsy for diagnosis of their underlying disease were prospectively enrolled. Sedation/analgesia was performed in all patients using remifentanil and propofol. The patients were simultaneously monitored using the CS and BIS. Results All sedations and muscle biopsies were performed uneventfully. The CS and BIS were significantly correlated (R = 0.589; P

There is only sparse data on the use of non-invasive ventilation (NIV) in acute respiratory failure (ARF) in infants and children. For this setting we investigated feasibility and efficacy of NIV and aimed to identify early predictors for treatment failure.Retrospective chart review was performed for all patients treated with NIV for ARF from 2003 to 2010 on an 8-bed pediatric intensive care unit of a tertiary university hospital.Seventy-four patients were treated with NIV. One patient did not tolerate mask ventilation and needed immediate invasive ventilation. Intubation rate of the remaining patients was 23% and mortality 15%. Institution of NIV led to significant improvement of both respiratory and heart rate in all patients within the first hour and to further stabilization within the next 8-10 hr. In patients with NIV success blood gases improved significantly 1-2 hr after starting NIV. Multivariate analysis identified low pH after 1-2 hr to be an individual risk factor for NIV failure. Other factors tested were age, underlying disease, acute respiratory insufficiency versus post-extubation failure (PEF), and 1-2 hr after starting NIV oxygen saturation, respiratory rate, PCO(2) , and FiO(2) . Patients with PEF tended to show better outcomes compared to those with acute respiratory insufficiency.NIV can be effective in infants and children with ARF. Low pH 1-2 hr after start of NIV is associated with NIV failure. It may therefore be useful in the decision to continue or stop mask ventilation.

Chronic exposure to chlorine gas has been shown to cause occupational asthma. Acute inhalation of chlorine is known to cause airway inflammation and induce airway nitric oxide formation. Exhaled nitric oxide may therefore be a marker of airway damage after chlorine gas exposure. After accidental chlorine gas exposure in a swimming pool, exhaled nitric oxide and pulmonary function were repeatedly measured in 18 children over a 1-mo period. Symptomatic children with impaired pulmonary function had higher nitric oxide levels on the day after the exposure compared to day 8 and day 28. Differences in exhaled nitric oxide were more pronounced at a higher exhalation flow compared to lower flow, suggesting peripheral rather than central airway damage. This was in accordance with the observed changes in pulmonary function. No changes in exhaled nitric oxide were seen in asymptomatic children. These data suggest that acute chlorine gas exposure results in a mild increase of exhaled nitric oxide in symptomatic children.

Argininosuccinic aciduria is an urea cycle disorder caused by argininosuccinate lyase (ASL) deficiency and is inherited as an autosomal-recessive trait. To date, mutation analysis has been limited because of incomplete sequence information about the human ASL gene. As a consequence, only 12 different mutations in 12 patients have been reported, so far. This study aimed at the completion of the structure and the sequence of the human ASL gene, the development of a genomic DNA-based system for mutation analysis and, finally, the characterisation of the molecular genetic background of ASL deficiency in 27 unrelated patients. This report provides transcript variants, the complete sequence of the human ASL gene and a complete ASL homologue on chromosome 22. The homologue was formerly thought to be a pseudogene but was found, in this study, to be correlated with an immunoglobulin-lambda-like mRNA. On the basis of the novel sequence data, a polymerase reaction chain system for mutation-screening in all 16 coding exons of the ASL gene was established and applied to the analysis of the ASL-deficient patients. We found mutations in all of the 54 investigated alleles and identified 23 (19 novel) different mutations. Some mutational hot-spots were identified (mainly in exons 4, 5, and 7) as were several predominant mutations: IVS5+1G--A (15 alleles), c.532G--A (7), c.346C--T (6), c.1153C--T (4). This study introduces a system for mutation analysis in the ASL gene, thereby elucidating the genetic background of ASL deficiency, which was found to be associated with considerable allelic heterogeneity.

A biochemical variant of argininosuccinate lyase deficiency, found in five individuals, is introduced. In comparison to classical patients, the variant cases of argininosuccinate lyase deficiency were characterized by residual enzyme activity as measured by the incorporation of [14C]citrulline into proteins. The five patients of different ethnic backgrounds presented with relatively mild clinical symptoms, variable age of onset, marked argininosuccinic aciduria and severe, but not complete, deficiency of argininosuccinate lyase. [14C]Citrulline incorporation into proteins, which is completely blocked in classical argininosuccinic aciduria, was only partially reduced in fibroblasts of these patients. Further investigation showed that previous standard conditions of the assay were not optimal. Higher concentrations of citrulline in the incubation medium strongly stimulated 14C incorporation in normal cells, but not in the patients; as a result, the relative incorporation level in the patients dropped to 6-28% compared to 18-75% of normal in the original procedure. Prenatal diagnosis was successfully performed in three of the families. Affected pregnancies were indicated by (partial) deficiency of [14C]citrulline incorporation in chorionic villi and/or increased levels of argininosuccinate in amniotic fluid. Analysis of the ASL gene in the five patients revealed a considerable allelic heterogeneity. Three novel mutations--R385C (2 patients), V178M and R379C--were detected in homozygous states, whereas one patient was compound heterozygous for the known mutations R193Q and Q286R. In conclusion, there are patients of different ethnic backgrounds who are characterized by residual activity of argininosuccinate lyase and who present with less severe clinical courses. In addition, we present an improved biochemical assay for accurate prenatal and postnatal diagnosis.