Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany.

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account.

[Increased rate of complications of pediatric acute otitis media and sinusitis in 2022/2023]. / Häufung von Komplikationen der akuten Otitis media und Sinusitis bei Kindern 2022/2023.

BACKGROUND: Acute mastoiditis and orbital complications of acute rhinosinusitis are among the most common complications of pediatric infections in otolaryngology. OBJECTIVE: The aim of this study was to investigate the frequency of pediatric acute mastoiditis in the setting of acute otitis media as well as pediatric orbital complications in the setting of acute rhinosinusitis. Data from before the pandemic were compared to data after the end of the COVID-19 restrictions. MATERIALS AND METHODS: Included were hospitalized children who presented with acute mastoiditis from acute otitis media or with orbital complications from acute rhinosinusitis during the period from April 2017 to March 2023. Compared were three periods using descriptive statistics: April 2017 to March 2020 (before the pandemic in Germany), April 2020 to March 2022 (during the contact restrictions of the pandemic), and April 2022 to March 2023 (after the contact restrictions were lifted). RESULTS: A total of 102 children (43 with acute mastoiditis, 42%, and 59 with orbital complications of acute sinusitis, 58%) were included. During the 2022/2023 period, more than twice as many children with acute mastoiditis and approximately three times as many children with orbital complications of acute rhinosinusitis were hospitalized compared to the average of the periods 2017/2018, 2018/2019, and 2019/2020. In the 2021/2022 period, the number of these patients was below the average of previous years. CONCLUSION: This year's seasonal cluster of upper respiratory tract infections is associated with a higher-than-average incidence of orbital complications and mastoiditis.

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).

BACKGROUND: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. METHODS: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. RESULTS: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. CONCLUSIONS: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.

Functional outcome after initial and multiple intracerebral hemorrhages in children with cerebral cavernous malformations.

BACKGROUND AND PURPOSE: We aimed to assess the course and predictors of functional outcome after single and multiple intracerebral hemorrhage (ICH) in pediatric patients with cerebral cavernous malformations (CCMs) and to conduct a risk assessment of a third bleed during the first follow-up year after second ICH. METHODS: We included patients aged ≤18 years with complete baseline characteristics, a magnetic resonance imaging dataset, ≥1 CCM-related ICH and ≥1 follow-up examination, who were treated between 2003 and 2021. Neurological functional status was obtained using modified Rankin Scale scores at diagnosis, before and after each ICH, and at last follow-up. Kaplan-Meier analysis was performed to determine the cumulative 1-year risk of third ICH. RESULTS: A total of 55 pediatric patients (median [interquartile range] age 12 [11] years) were analyzed. Univariate analysis identified brainstem cavernous malformation (BSCM; p = 0.019) as a statistically significant predictor for unfavorable outcome after second ICH. Outcome after second ICH was significantly worse in 12 patients (42.9%; p = 0.030) than after first ICH and in five patients (55.6%; p = 0.038) after a third ICH compared to a second ICH. Cumulative 12-month risk of rebleeding during the first year after a second ICH was 10.7% (95% confidence interval 2.8%-29.37%). CONCLUSIONS: Pediatric patients with a BSCM have a higher risk of worse outcome after second ICH. Functional outcome improves over time after an ICH but worsens following each ICH compared to baseline or previous ICH. Second bleed was associated with neurological deterioration compared to initial ICH, and this deteriorated further after a third ICH.

Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents.

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.

[Time to Antibiotics (TTA) - Reassessment from the German Working Group for Fever and Neutropenia in Children and Adolescents (DGPI/GPOH)]. / Time to Antibiotics (TTA) ­ Überlegungen der Arbeitsgruppe Fieber bei Granulozytopenie im Kindes- und Jugendalter (GPOH/DGPI) zu einer Neubewertung.

BACKGROUND: The current German guidance from 2016 recommends a Time to Antibiotics (TTA) of<60 min in children and adolescents with febrile neutropenia (FN). METHODS: Critical analysis of available studies and recent meta-analyses, and discussion of the practical consequences in the FN working group of the German Societies for Paediatric Oncology and Haematology and Paediatric Infectious Diseases. RESULTS: The available evidence does not support a clinically significant outcome benefit of a TTA<60 min in all paediatric patients with FN. Studies suggesting such a benefit are biased (mainly triage bias), use different TTA definitions and display further methodical limitations. In any case, a TTA<60 min remains an essential component of the 1st hour-bundle in paediatric cancer patients with septic shock or sepsis with organ dysfunction. CONCLUSION: Provided that all paediatric FN patients receive a structured medical history and physical examination (including vital signs) by experienced and trained medical personnel in a timely fashion, and provided that a sepsis triage and management bundle is established and implemented, a TTA lower than 3 hours is sufficient and reasonable in stable paediatric cancer patients with FN.

[Pediatric neurocritical care]. / Pädiatrische Neurointensivmedizin.

Pediatric neurocritical care requires multidisciplinary expertise for the care of critically ill children. Approximately 14-16% of critically ill children in pediatric intensive care suffer from a primary neurological disease, whereby cardiac arrest and severe traumatic brain injury play major roles in Europe. The short-term goal of interventions in the pediatric intensive care unit is to stabilize vital functions, whereas the overarching goal is to achieve survival without neurological damage that enables fulfillment of the individual developmental physiological potential. For this reason, evidence-based methods for brain monitoring during the acute phase and recovery are necessary, which can be performed clinically or with technical devices. This applies to critically ill children with primary neurological diseases and for all children at risk for secondary neurological insults. Patients with diseases of the peripheral nervous system are also treated in pediatric intensive care medicine. In these patients, the primary aim frequently consists of bridging the time until recovery after acute deterioration, for example during an infection. In these patients, monitoring the cerebral function can be especially challenging, because due to the underlying disease the results of the examination cannot be interpreted in the same way as for previously neurologically healthy children. This article summarizes the complexity of pediatric neurocritical care by presenting examples of diagnostic and therapeutic approaches in the context of various neurological diseases that can be routinely encountered in the pediatric intensive care unit and can only be successfully treated by multidisciplinary teams.

Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. METHODS: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. RESULTS: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15-8.63]; P=0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04-5.86]; P=0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18-8.99]; P=0.022 and odds ratio, 2.53 [95% CI, 1.07-5.98]; P=0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80-110.39]; P=0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%-23.6%) for the entire cohort, 30.2% (20.2%-42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%-51.1%) for children with brain stem CCM. CONCLUSIONS: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

Antibiotics in critically ill children-a narrative review on different aspects of a rational approach.

Especially critically ill children are exposed to antibiotic overtreatment, mainly caused by the fear of missing out a severe bacterial infection. Potential adverse effects and selection of multi-drug resistant bacteria play minor roles in decision making. This narrative review first describes harm from antibiotics and second focuses on different aspects that could help to reduce antibiotic overtreatment without harming the patient: harm from antibiotic treatment, diagnostic approaches, role of biomarkers, timing of antibiotic therapy, empiric therapy, targeted therapy, and therapeutic drug monitoring. Wherever possible, we linked the described evidence to the current Surviving Sepsis Campaign guidelines. Antibiotic stewardship programs should help guiding antibiotic therapy for critically ill children. IMPACT: Critically ill children can be harmed by inadequate or overuse of antibiotics. Hemodynamically unstable children with a suspicion of infection should be immediately treated with broad-spectrum antibiotics. In contrast, in hemodynamically stable children with sepsis and organ dysfunction, a time frame of 3 h for proper diagnostics may be adequate before starting antibiotics if necessary. Less and more targeted antibiotic treatment can be achieved via antibiotic stewardship programs.

Bronchial artery diameter in massive hemoptysis in cystic fibrosis.

BACKGROUND: Massive hemoptysis is a rare but potentially life-threatening condition of patients with cystic fibrosis (CF) and advanced pulmonary disease. Hypertrophied bronchial arteries are understood to cause massive hemoptysis when rupturing. Risk factors to predict massive hemoptysis are scarce and bronchial artery diameters are not part of any scoring system in follow-up of patients with CF. Aim of this study was to correlate bronchial artery diameter with massive hemoptysis in CF. METHODS: Bronchial artery and non-bronchial systemic artery diameters were measured in contrast enhanced computed tomography (CT) scans in patients with massive hemoptysis and compared to patients with end-stage CF and no history of hemoptysis. Demographic and clinical data and side of bronchial artery/non-bronchial systemic artery hypertrophy and coil embolization were documented. RESULTS: In this retrospective multicenter study 33 patients with massive hemoptysis were included for bronchial artery/non-bronchial systemic artery diameter measurements, (13 female, 20 male, median age 30 years (18-55)). Bronchial artery diameters were significantly larger in the case group than in the control group with median 4 mm (2.2-8.2 mm), and median 3 mm (1-7 mm), respectively (p = 0.002). Sensitivity of bronchial arteries ≥ 3.5 mm to be associated with hemoptysis was 0.76 and specificity 0.71 with ROC creating an area under the curve of 0.719. If non-bronchial systemic arteries were present, they were considered culprit and embolized in 92% of cases. CONCLUSION: Bronchial arteries ≥ 3.5 mm and presence of hypertrophied non-bronchial systemic arteries correlate with massive hemoptysis in patients with CF and might serve as risk predictor for massive hemoptysis. Therefore, in patients with advanced CF we propose CT scans to be carried out as CT angiography to search for bronchial arteries ≥ 3.5 mm and for hypertrophied non-bronchial systemic arteries as possible risk factors for massive hemoptysis.

NAT2 polymorphisms as a cause of metamizole-induced agranulocytosis.

Metamizole is a widely prescribed NSAID with excellent analgesic and antipyretic properties. Although very effective, it is banned in some countries because of the risk for severe agranulocytosis. We here describe three patients with metamizole-associated agranulocytosis. Patient #1 suffered from agranulocytosis and tonsillitis followed by severe sepsis by Streptococcus pneumoniae and Epstein-Barr virus reactivation. Her dizygotic twin sister (patient #2) also suffered from agranulocytosis after a surgical intervention. Patient #3 initially had a tonsillitis and also developed neutropenia after metamizole intake. For all patients, pharmacogenetic diagnostic for the genes CYP2C9, CYP2C19 and NAT2, which are involved in metamizole metabolism and degradation of toxic metabolites, was initiated. Pharmacogenetic analysis revealed NAT2 slow acetylator phenotype in all three patients. Additionally, patient #2 is an intermediate metabolizer for CYP2C19 and patient #3 is a poor metabolizer for CYP2C9. Impairment of these enzymes causes a reduced degradation of toxic metabolites, for example, 4-methylaminoantipyrine (4-MAA) or 4-aminoantipyrine. The metabolite 4-MAA can complex with hemin, which is an early breakdown product during hemolysis. Hemolysis is often observed during invasive infections or after surgical procedures. It is known that the 4-MAA/hemin complex can induce cytotoxicity in the bone marrow and interrupt granulocyte maturation. In conclusion, metamizole-induced agranulocytosis most likely was a consequence of the underlying genetical predisposition, that is, polymorphisms in the genes NAT2, CYP2C9 and CYP2C19. Hemolysis may have increased the toxicity of metamizole metabolites.

aEEG as a useful tool for neuromonitoring in critically ill children - Current evidence and knowledge gaps.

AIM: Amplitude-integrated electroencephalography (aEEG) is used in children beyond neonatal age, but systematic investigations have been lacking. This mini-review summarised aEEG studies on children aged one month to 18 years, evaluated the usefulness of aEEG and identified knowledge gaps or limitations. METHODS: We searched the PubMed database for articles published in English up to September 2020, and 23 papers were identified. RESULTS: aEEG was frequently used to compensate for the absence of continuous full-channel EEG monitoring, particularly for detecting seizures. Interpreting background patterns was based on neonatal classifications, as reference values for older infants and children are lacking. It is possible that aEEG could predict outcomes after paediatric cardiac arrests and other conditions. Gaps in our knowledge exist with regard to normal values in healthy children and the effects of sedation on aEEG background patterns in children. CONCLUSION: The main application of aEEG was detecting and treating paediatric seizures. Further research should determine reference values and investigate the potential to predict outcome after critical events or in acute neurological disease. It is likely that aEEG will play a role in paediatric critical care in the future.

Bacterial infections in children after liver transplantation: A single-center surveillance study of 345 consecutive transplantations.

BACKGROUND: Infectious complications after pediatric liver transplantation frequently occur and are potentially serious. Data concerning strictly defined bacterial infections and their associated risk factors are lacking. METHODS: For the pediatric liver transplant postoperative period, we analyzed data from the nosocomial infection surveillance (2006-2015). RESULTS: A total of 235 bacterial infections in 162 transplantations (47%) occurred, including 32 bacterial pneumonia cases, 104 surgical site infections, 27 urinary tract infections, and 40 bloodstream infections. Sepsis was diagnosed in 127 cases (54%), severe sepsis in 22 (9%) cases, and septic shock in 41 (17%) cases. Thirty patients (9%) died, and septic shock was the leading cause of death. The carrier status of multi-drug resistant bacteria and a tacrolimus level >20 ng/mL were independent risk factors for surgical site infections and the occurrence of severe sepsis or septic shock. The length of mechanical ventilation was an independent risk factor for pneumonia and surgical site infection. CONCLUSION: Bacterial infections in the early postoperative period after pediatric liver transplantation are associated with high morbidity and mortality. Physicians involved in the medical care of these patients should be aware of the specific risk factors, and further development of prevention programs is highly recommended.

A DELPHI study on aspects of study design to overcome knowledge gaps on the burden of disease caused by serogroup B invasive meningococcal disease.

BACKGROUND: Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. METHODS: We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. RESULTS: Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients' QoL. CONCLUSIONS: Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

Visual Distraction During Sleep Induction with Propofol in Pediatric Patients - Can Cartoon Watching Influence the Sedative Dose?

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: Children watching a standard cartoon during sleep induction for deep sedation have a shorter sleep onset time but sedative dose is not reduced.

Undue Elevation of Procalcitonin in Pediatric Paracetamol Intoxication is Not Explained by Liver Cell Injury Alone.

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 Influence of BIS Monitoring on Sedative Dose in Pediatric Patients Undergoing Open Muscle Biopsies - a Randomized Controlled Trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Differences of Medical Care for Acute Severe Viral Bronchiolitis in Two Urban Areas in Europe.

BACKGROUND: Acute viral bronchiolitis is a frequent disease in infancy. There is little knowledge on medical care of severely affected infants in different European countries. PATIENTS: Infants (n=146) with bronchiolitis requiring respiratory support in winter season 2015/2016 treated in either one of two regions in Central Europe: South of greater Paris region in France (group 1) and Ruhr area in Germany (group 2). METHODS: Retrospective chart review. Primary outcome parameter was duration of respiratory support. RESULTS: Infants in group 1 (n=96) were younger, suffered less frequently from neurologic disorders and had lower respiratory rates than in group 2 (n=50). CO2 levels and dyspnea score were similar. Ninety percent of infants in group 1 were treated by nasal Continuous Airway Pressure CPAP, while 80% of infants in group 2 were treated by High Flow Nasal Cannula HFNC. Duration of respiratory support was significantly shorter in group 1. Infants in group 2 received more frequently infusion therapy, more antibiotics and more inhalation therapy. DISCUSSION: Our results show better outcome for infants with viral bronchiolitis treated in France. Striking differences were the practice of respiratory support (nasal CPAP vs. HFNC) and the prescription of supportive treatments. CONCLUSION: Treatment approaches in severe acute viral bronchiolitis differ widely between a French and a German urban region.

The influence of parents' voice on the consumption of propofol for pediatric procedural sedation-a randomized controlled trial.

BACKGROUND: 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.

Prospective evaluation of SeptiFast Multiplex PCR in children with systemic inflammatory response syndrome under antibiotic treatment.

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 < 0.05). All blood cultures and 13 of 14 positive SF-tests were considered infection. Median time for positive BC was 2 days, and time to definite result was 6 days, compared to 12 h for SF. Antimicrobial therapy was adapted in 7 of the 14 patients with positive SeptiFast, and in 3 of the 4 patients with positive BC. Best predictive power for positive SF shown by receiver-operating characteristic was demonstrated for procalcitonin PCT (Area under the curve AUC: 0.79), compared to C-reactive protein CRP (AUC: 0.51) and leukocyte count (AUC: 0.46). A procalcitonin threshold of 0.89 ng/ml yielded a sensitivity of 0.82 and a specifity of 0.7. Children with a positive SeptiFast result on day 0 had a significantly higher risk to require treatment on the Pediatric Intensive Care Unit or to be deceased on day 30 (Odds-Ratio 8.62 (CI 1.44-51.72). CONCLUSIONS: The additional testing with SeptiFast in antimicrobially pre-treated children with systemic inflammation enhances the rate of pathogen detection. The influence of multiplex PCR on clinically relevant outcome parameters has to be further evaluated. ( TRIAL REGISTRATION: DRKS00004694).