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Background In critically ill children, detection of intra-abdominal hypertension (IAH > 10 mmHg) and abdominal compartment syndrome (ACS = IAH + organ dysfunction) is paramount and usually monitored through intra-vesical pressures (IVP) as current standard. IVP, however, carries important disadvantages, being time-consuming, discontinuous, with infection risk through observer-dependent manipulation, and ill-defined for catheter sizes. Therefore, we sought to validate air-capsule-based measurement of intra-gastric pressure (ACM-IGP). Methods We prospectively compared ACM-IGP with IVP both in vivo and in vitro (water column), according to Abdominal-Compartment-Society validation criteria. We controlled for patient age, admission diagnosis, gastric filling/propulsive medication, respiratory status, sedation levels and transurethral catheters, all influencing intra-abdominal pressure (IAP). Results In tertiary care PICU setting, finally, n = 97 children were enrolled (median age, 1.3 years [range 0 days–17 years], LOS-PICU 8.0 [1–332] days, PRISM-III-Score 13 [0–35]). In n = 2.770 measurements pairs, median IAP was 6.7 [0.9–23.0] mmHg, n = 38 (39%) children suffered from IAH > 10 mmHg, n = 4 from ACS. In vitro against water column, ACM-IGP correlated perfectly (r2 0.99, mean bias − 0.1 ± 0.5 mmHg, limits of agreement (LOA) − 1.1/+ 0.9, percentage error [PE] 12%) as compared with IVP (r2 0.98, bias + 0.7 ± 0.6 mmHg, LOA − 0.5/+ 1.9, PE 15%). With larger IVP catheters at higher pressure levels, IVP underestimated pressures against water column. In vivo, agreement between either technique was strong (r2 0.95, bias 0.3 ± 0.8 mmHg, LOA − 1.3/+ 1.9 mmHg, PE 23%). No impact of predefined control variables on measurement agreement was observed. Conclusions In a large PICU population with high IAH prevalence, ACM-IGP agreed favourably with IVP. More widespread usage of ACM-IGP may improve detection rates of ACS in critically ill children. Trial registration WHO-ICTRP-No. DRKS00006556 (German Clinical Trial Register). Registered 12th September 2014, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006556

Introduction: Liver transplantation (LT) in children has undergone significant changes over the last years. Especially the use of split and living donor transplants even for infants has led to new challenges in pre- and post-operative care. Systemic inflammatory response syndromes (SIRS, sepsis) as well-known complications after LT have not yet been systematically examined in the pediatric population. Methods: We analyzed clinical data of 39 pediatric liver transplant recipients regarding potential risk factors for post-transplant SIRS and sepsis. Secondly, the prognostic impact of SIRS and sepsis on post-transplant clinical course, patient and transplant-survival has been analyzed. Results: 64% of patients developed either SIRS (n = 16, 41%) or sepsis (n = 9, 23%) within 30 days after transplantation. No pre-transplant risk factors for increased susceptibility for SIRS or sepsis could be identified. Secondary closure of the abdomen (p = 0.045) and secondary biliary reconstruction (p = 0.043) were associated with a higher incidence of sepsis and were associated with significantly prolonged mechanical ventilation times in the presence of sepsis (p = 0.001). Patients with sepsis, but not SIRS, stayed significantly longer on PICU (p = 0.021) and suffered from higher mortality (n = 3 versus 0; p = 0.0006). All deaths within 30 days of transplantation were due to septic multiorgan failure. Neither early SIRS nor sepsis were associated with loss of transplant function. Conclusions: SIRS and sepsis are frequent events after pediatric liver transplantation. Sepsis increased length of PICU-stay and mortality significantly and prolonged duration of mechanical ventilation. Secondary biliary reconstruction and closure of the abdomen could be identified as potential risk factors for sepsis.

Background The aim of the present study was to assess whether paediatric intensive care units (PICUs) in three central European countries comply with guidelines concerning infrastructure provided by the European Society of Intensive Care Medicine (ESICM). Between July 2016 and May 2017, a survey was conducted based on the ESICM guidelines. The questionnaire was structured into four categories: structural quality, diagnostic/therapeutic equipment, personnel and organization. All PICUs treating paediatric patients in the D–A–CH region [Germany (D), Austria (A) and Switzerland (CH)] were researched through the national societies. A total of 126 PICUs were contacted (D: 106; A: 12; and CH: 8). Results Eighty-five of 126 PICUs responded (D: 67%; A: 61%; and CH: 100%). A median of 500 patients was treated annually (D: 500; A: 350; and CH: 600) with a median of 12 beds (D: 12; A: 8; and CH: 12). Recommendations regarding infrastructure were met as follows: structural quality 62% in D, 71% in A and 75% in CH; diagnostic/therapeutic equipment: 87% in D, 91% in A and 89% in CH; personnel: 65% in D, 87% in A and 85% in CH; and organization: 75% in D, 73% in A and 88% in CH. Conclusions This survey reveals deficits concerning structural quality in all countries. Furthermore, shortcomings regarding personnel were found in Germany and for organization in Germany and Austria. These issues need to be addressed urgently to further improve treatment quality and patient safety in the future. Electronic supplementary material The online version of this article (10.1186/s13613-018-0451-1) contains supplementary material, which is available to authorized users.

The need for filtering intravenous infusions has long been recognized in the field of venous access, though hard scientific evidence about the actual indications for in-line filters has been scarce. In the last few years, several papers and a few clinical studies have raised again this issue, suggesting that the time has come for a proper definition of the type of filtration, of its potential benefit, and of its proper indications in clinical practice. The WoCoVA Foundation, whose goal is to increase the global awareness on the risk of intravenous access and on patients’ safety, developed the project of a consensus on intravenous filtration. A panel of experts in different aspects of intravenous infusion was chosen to express the current state of knowledge about filtration and to indicate the direction of future research in this field. The present document reports the final conclusions of the panel.

Background The COVID-19 pandemic has disrupted healthcare systems worldwide. In addition to the direct impact of the virus on patient morbidity and mortality, the effect of lockdown strategies on health and healthcare utilization have become apparent. Little is known on the effect of the pandemic on pediatric and adolescent medicine. We examined the impact of the pandemic on pediatric emergency healthcare utilization. Methods We conducted a monocentric, retrospective analysis of n = 5,424 pediatric emergency department visits between January 1st and April 19th of 2019 and 2020, and compared healthcare utilization during the pandemic in 2020 to the same period in 2019. Results In the four weeks after lockdown in Germany began, we observed a massive drop of 63.8% in pediatric emergency healthcare utilization (mean daily visits 26.8 ± SEM 1.5 in 2019 vs. 9.7 ± SEM 1 in 2020, p p p Conclusions Our data illustrate a significant decrease in pediatric emergency department visits during the COVID-19 pandemic. Public outreach is needed to encourage parents and guardians to seek medical attention for pediatric emergencies in spite of the pandemic.

Background High resolution mass spectrometry (HRMS) is being used increasingly in the context of suspect and non-targeted screening for the identification of bioorganic molecules. There is correspondingly increasing awareness that higher confidence identification will require a systematic, group effort to increase the fraction of compounds with tandem mass spectra available in central, publicly available resources. While typical suspect screening efforts will only result in tentative annotations with a moderate level of confidence, library spectral matches will yield higher confidence or even full confirmation of the identity if the reference standards are available. Results This article first explores representative percent coverage of measured tandem mass spectra in selected major environmental suspect databases of interest in the context of human biomonitoring, demonstrating the current extensive gap between the number of potential substances of interest (up to hundreds of thousands) and measured spectra (0.57–3.6% of the total chemicals have spectral information available). Furthermore, certain datasets are benchmarked, based on previous efforts, to show the extent to which acquired experimental data were comparable between laboratories, even with HRMS instruments based on different technologies (i.e., quadrupole–quadrupole-time of flight versus ion trap/quadrupole-Orbitrap). Instruments and settings that are less comparable are also revealed, primarily linear ion trap instruments, which show distinctly lower comparability. Conclusions Based on these efforts, harmonization guidelines for the acquisition and processing of tandem mass spectrometry data are proposed to enable European (and ideally worldwide) laboratories to contribute to common resources, without requiring extensive changes to their current in house methods.

Background Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). Methods This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. Results A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70–0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52–0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87–100%), 28% (95% CI: 20–38%) of non-infectious SIRS cases were assorted correctly. Conclusions Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices. Trial registration ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005. Electronic supplementary material The online version of this article (10.1186/s12887-018-1082-2) contains supplementary material, which is available to authorized users.

Congenital ornithine transcarbamylase deficiency (OTCD, OMIM 311250, Xp21.1) in humans results in hyperammonaemia with subsequent neurological symptoms including hypotonia, seizures and mental retardation. At the age of 3 years a hyperkinetic-hyperactive behaviour disorder of unknown origin was diagnosed in our female patient. The girl, ultimately diagnosed as having OTCD presented at the age of 6 years with an episode of feverassociated metabolic stroke including coma, epilepsy and further neurological symptoms due to hyperammonaemia. The pattern of plasma amino acids, the elevated level of orotic acid in urine and mutation analysis confirmed the diagnosis of OTCD. The possibility of early diagnosis and therapy of a disease which otherwise leads to severe neurological and psychiatric sequelae emphasizes the importance of precise evaluation of a possible organic cause for hyperkinetic-hyperactive behaviour disorders. This case of late-onset OTCD demonstrates that total recovery is possible even after a long comaepisode with slow reconvalescence. (J Pediatr Neurol 2004; 2(2): 97-100).

In pediatric patients with acute refractory cardiogenic shock (CS), extracorporeal membrane oxygenation (ECMO) remains an established procedure to maintain adequate organ perfusion. In this context, ECMO can be used as a bridging procedure to recovery, VAD or transplantation. While being supported by ECMO, most centers tend to keep their patients well sedated and supported by invasive ventilation. This may be associated with an increased risk of therapy-related morbidity and mortality. In order to optimize clinical management in pediatric patients with ECMO therapy, we report our strategy of veno-arterial ECMO (VA-ECMO) in extubated awake and conscious patients. We therefore present data of six of our patients with CS, who were treated by ECMO being awake without continuous analgosedation and invasive ventilation. Of these six patients, four were1 year and two14 years of age. Median time on ECMO was 17.4 days (range 6.9-94.2 days). Median time extubated, while receiving ECMO support was 9.5 days. Mean time extubated was 78 % of the total time on ECMO. Three patients reached full recovery of cardiac function on "Awake-VA-ECMO," whereas the other three were successfully bridged to destination therapy (VAD, heart transplantation, withdrawal). Four out of our six patients are still alive. Complications related to ECMO therapy (i.e., severe bleeding, site infection or dislocation of cannulas) were not observed. We conclude that "Awake-VA-ECMO" in extubated, spontaneously breathing conscious pediatric patients is feasible and safe for the treatment of acute CS and can be used as a "bridging therapy" to recovery, VAD implantation or transplantation.

Bridging critically ill pediatric patients to lung transplantation still remains a major challenge. Although still controversial, within the last 5 years, ECMO has been increasingly used as a bridge to lung transplantation concept in adult and pediatric patients with acceptable outcomes. The outstanding developments in the field of extracorporeal devices and the introduction of awake ECMO concepts with the avoidance of mechanical ventilation have led to a real paradigm shift in the ICU management of pretransplant candidates with severe respiratory failure. Therefore, ECMO is no longer seen as a contraindication for lung transplantation at least at our center. Nevertheless, how to bridge these patients on ECMO still remains controversial. Thus, we introduced an ambulatory ECMO approach in adolescent lung transplant candidates with acute respiratory failure using a dual cannulation strategy and hereby present first results from this procedure.

BACKGROUND Systemic inflammatory response syndrome (SIRS) is frequent after cardiac surgery, but data on its incidence and perioperative risk factors are scarce for children with congenital heart disease. METHODS SIRS incidence within 72 hours following cardiac surgery was evaluated in a secondary analysis of children enrolled to a treatment-free control group of a randomized controlled trial. Intraoperative parameters were investigated for their association with SIRS using multivariable fractional polynomial logistic regression models. Effects of SIRS on various organ functions and length of stay were evaluated using time-varying Cox regression models. RESULTS In 116 children after cardiac surgery (median age [range]: 7.4 month [1 day-16.2 years]) SIRS occurred in n = 39/102 with and n = 1/14 without cardiopulmonary bypass (CPB). Duration of CPB (hazard ratio [HR]: 2.28 per hour; 95% confidence interval [CI] 1.17; 4.42) and amount of fresh frozen plasma (HR: 1.23 per 10 mL/kg; 95%CI 1.06; 1.42) were identified as predictors for SIRS; neonates seemed to be less susceptible for SIRS development (HR: 0.86; 95%CI 0.79; 0.95). SIRS was associated with organ dysfunction (HR: 2.69; 95%CI 1.41; 5.12) and extended stay in the pediatric intensive care unit (PICU) (median: 168 vs. 96 hours; p = 0.007). CONCLUSIONS SIRS is a frequent complication after pediatric congenital heart surgery; it affects nearly one third of children and prolongs PICU stay significantly. Duration of CPB and amount of fresh frozen plasma were identified as important risk factors. Neonates seem to be less susceptible to SIRS development.

Uber eine erfolgreiche Lungentransplantation (LTx) bei bronchopulmonaler Dysplasie (BPD) vor dem 5. Lebensjahr liegen bislang kaum Erfahrungsberichte vor. Im Folgenden wird der Fall eines 3-Jahrigen beschrieben. Wie sich nach der LTx herausstellte litt der Patient an einer seltenen kongenitalen alveolaren Dysplasie ohne Misalignement der Pulmonalvenen.

Arterial thrombosis in neonates and children is a rare event and is often associated with external risk factors such as asphyxia or sepsis. We report our experiences with two neonates with spontaneous aortic arch thrombosis mimicking aortic coarctation. Despite single case reports until now, no data exist for the underlying thrombophilic risk factors and prognosis of this rare event. Both patients were carriers of a heterozygous factor V Leiden mutation, which has been reported once before as a risk factor for aortic arch thrombosis. One of our patients was operated upon successfully and is alive. The second patient suffered a large infarction of the right medial cerebral artery and had a thrombotic occlusion of the inferior caval vein. The patient obtained palliative care and died at the age of 6 days. In the literature, we identified 19 patients with neonatal aortic arch thrombosis. Of the 19 patients, 11 (58%) died. Including the two reported patients, the mortality rate of patients with multiple thromboses was 80% (8/10) compared with 18% (2/11) for patients with isolated aortic arch thrombosis; this difference reached statistical significance (p = 0.009). The analysis of thrombophilic disorders revealed that factor V Leiden mutation and protein C deficiency seem to be the most common risk factors for aortic arch thrombosis.Conclusion:Neonatal aortic arch thrombosis is a very rare but life-threatening event, with a high rate of mortality, especially if additional thrombotic complications are present. Factor V Leiden mutation seems to be one important risk factor in the pathogenesis of this fatal disease.

Purpose Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients. Methods This single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed. Findings Analysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97−4.82] vs. 2.98 [2.33−3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6−22.4] vs. 11.0 [7.1−14.9] h; P = 0.028) were significantly reduced. Conclusion In-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768). Electronic supplementary material The online version of this article (doi:10.1007/s00134-012-2539-7) contains supplementary material, which is available to authorized users.

Especially in critically ill children with cardiac diseases, fluid management and monitoring of cardiovascular function are essential. Ultrasound dilution technique (UDT) was recently introduced to measure cardiac output (CO) and volumetric parameters, such as intrathoracic and end-diastolic blood volume. We compared UDT with the well-established transpulmonary thermodilution (TPTD) method (PiCCO) for determining CO measurements and derived volumes in a juvenile animal model. Experiments were performed in 18 ventilated, anesthetized piglets during normovolemia and after isovolemic hemodilution. At baseline and 20 min after each step of isovolemic hemodilution, 3 independent measurements of CO and volumetric parameters were conducted with TPTD and UDT, consecutively, under hemodynamically stable conditions. We observed comparable results for CO measurements with both methods (mean 1.98 l/min; range 1.12-2.87) with a percentage error of 17.3% (r = 0.92, mean bias = 0.28 l/min). Global end-diastolic volume (GEDV) and intrathoracic blood volume (ITBV) by TPTD were almost two times greater than analogous volumes [central blood volume (CBV); total end-diastolic volume (TEDV)] quantified by UDT (CBV = 0.58 × ITBV + 27.1 ml; TEDV = 0.48 × GEDV + 23.1 ml). CO measurements by UDT were found to be equivalent and hence interchangeable with TPTD. Discrepancies in volumetric parameters could either be due to the underlying algorithm or different types of indicators (diffusible vs. nondiffusible). Compared with the anatomically defined heart volume, TPTD seems to overestimate end-diastolic volumes. Future studies will be necessary to assign these results to critically ill children and to validate volumetric parameters with reference techniques.

With the aim of determining long-term outcome, the authors approached 38 families (average 2.1 years after trauma) with a questionnaire, following the acute-clinical treatment of head trauma of their children. Long-term damage was restricted almost exclusively to patients presenting with a Glasgow Coma Score ≤8. Paresis (16%), cranial nerve damage (13%), incontinence (5%), or coordinative disturbances (18%) continued. The older children stated that they influenced their life to a great extent (11%). Furthermore, many had mental and cognitive problems that occur quite frequently even in children with light head trauma and often only manifest after release from hospital. This causes problems and results in inferior performance (26%), especially at school, which is further complicated through lengthy periods of absence. The parents, especially, mentioned behavioral problems such as social withdrawal or aggressive demeanor, which led to tension also inside the family. A persistent vegetative state is rare after head trauma in children.

Levosimendan is a calcium-sensitizing agent with effective inotropic properties. It has been shown to improve cardiac function, hemodynamic performance, and survival in adults with severe heart failure. However, the effect of Levosimendan in pediatric cardiac surgery has not yet been investigated. Thus, we report on our experience with the intraoperative application of Levosimendan in seven infants (body weight range 2.6-6.3 kg) with severe myocardial dysfunction after complex congenital heart surgery. During the administration of Levosimendan, the heart rate, mean arterial blood pressure, and central venous pressure did not change. The mean arterial lactate level significantly decreased 24 and 48 h after the first infusion compared to baseline. Central venous oxygen saturation increased significantly 24 and 48 h after the onset of Levosimendan infusion. We found intraoperatively administered Levosimendan to be well tolerated in the seven infants with severe myocardial dysfunction after complex congenital heart surgery. Levosimendan is a new rescue drug which has beneficial effects, even in pediatric cardiac surgery.

Acute respiratory distress syndrome, with the need for invasive mechanical ventilation (MV) remains a major cause of neonatal mortality and morbidity. Although venovenous extracorporeal lung support (VV-ECLS) has become a standard of care procedure in neonatal patients with acute pulmonary failure there are no reports regarding the use of a double-lumen cannula for extracorporeal minimal invasive lung support via the umbilical vein. A neonatal lamb model was used (n = 3). Umbilical vein was cannulated with a double-lumen catheter allowing venovenous extracorporeal gas exchange. Cannula was positioned with its tip in the right atrium. VV-ECLS was started and ventilation was stopped. Providing oxygenation and CO2 removal solely through VV-ECLS hemodynamics, blood gases were measured. Total VV-ECLS without MV was applied to all three neonatal lambs. Time on venovenous ECLS was 60, 120 and 120 min. Initial pCO2 was 60, 56 and 65 mmHg compared to 31, 32 and 32 mmHg at the end of VV-ECLS. Initial pO2 was 30, 27 and 26 mmHg compared to 22, 19 and 23 mmHg. Initial lactate was 5, 10 and 3.7 mmol/l compared to 13.3, 12.6 and 11.3 mmol/l at the end of VV-ECLS. MAP at baseline was 51, 52 and 65 mmHg compared to 36, 38 and 41 mmHg at the end of VV-ECLS. In all three lambs inotropes were admitted to maintain MAD >35 mmHg. Even without mechanical ventilation we were able to sufficiently remove pCO2 with our new minimal invasive VV-ECLS using a double-lumen catheter via the umbilical vein, supporting the idea of a lung protective strategy in neonatal acute respiratory failure. pO2 was measured 22, 19 and 23 mmHg, respectively, at the end of VV-ECLS, at least partially caused by recirculation phenomenon, which could possibly be improved by different cannula design. Inotropic support was necessary during VV-ECLS to achieve targeted MAD > 35 mmHg. While technically feasible, this new approach might allow further research in the field of extracorporeal lung support and therefore will follow the concept of a lung protective strategy in acute neonatal respiratory failure.

Adenoviral (AdV) infections after transplantation remain a challenge in pediatric patients. Qualitative and quantitative PCR offer new approaches to early diagnosis and monitoring. However, their role in the management of AdV infections in pediatric transplant recipients remains to be determined. We report six children with positive qualitative serum-PCR for AdV on routine follow-up after transplantation (liver n = 4, hematopoetic stem cells (HSCT) n = 1, combined liver and HSCT n = 1). None of these children were symptomatic at the time of first detection of AdV. Two patients remained asymptomatic, one developed hemorrhagic cystitis and enteritis. Three children with positive PCR developed high viral load on quantitative PCR, all developed clinical AdV sepsis with further rising virus load. Despite antiviral therapy with cidofovir, these three patients died of septic multiorgan failure. Positive qualitative AdV-PCR from blood after pediatric transplantation is not necessarily followed by clinical disease. In case of positive AdV-PCR, monitoring by serial quantitative PCR is useful regarding treatment decision and prevention of fatal disease.

Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (−11.3 %; 95 % CI −21.8 to −0.5 %), renal (−10.0 %; 95 % CI −17.0 to −3.0 %) and hematologic (−8.1 %; 95 % CI −14.2 to −0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care. Electronic supplementary material The online version of this article (doi:10.1007/s00246-015-1157-x) contains supplementary material, which is available to authorized users.

The objective of this non-interventional, international registry was to collect and assess data on the indications, safety, and the outcomes of treatment of patients with acquired protein C deficiency with a plasma-derived, human non-activated protein C concentrate (Ceprotin, Baxalta/Shire). Any patient who received treatment with protein C concentrate was eligible for the study; there were no exclusion criteria. This was an observational study with no required predefined visits, medical or laboratory tests, procedures or interventions either at enrollment or during the study. The study was conducted from June 2010 to June 2015. Management of patients was according to the discretion of the investigator. The primary endpoints were the medical diagnoses associated with protein C concentrate treatment, the protein C concentrate treatment regimens (dose, frequency), treatment outcomes and safety information. Here we report the results from 18 patients with severe acquired protein C deficiency (SAPCD - as judged by the treating physician) from 4 European (EU) investigative sites. Protein C concentrate is not currently approved for treatment of acquired protein C deficiency in the EU. The median age at study entry was 1.9 years (range: birth to 73.1 years); 5 [27.8%] patients were Eighteen patients were treated with protein C concentrate. At clinical presentation, 15/18 (83.3%) of these patients had sepsis, 2 had necrotizing enterocolitis and 1 had hemolytic uremic syndrome. Thromboembolic disease was present in 8/18 (25.8%) patients, all of whom had purpura fulminans. Of these 8 patients, 2 had disseminated intravascular coagulation (DIC) in addition to other conditions; 1 patient also had arterial thrombosis, and the other patient had macrovascular thrombosis and skin necrosis. The remaining 10 (74.2%) patients had no evidence of thromboembolic disease: of these, 7 patients had sepsis, 2 necrotizing enterocolitis and 1 hemolytic uremic syndrome. Dose level and frequency were variable: the most common dosage was 100 IU/kg and the most common interval between doses was 6 hours. There were no infusions administered for surgical interventions or for prophylaxis. At the time of final analysis 17/18 (94.4%) of patients had at least one follow-up visit. The median duration of study participation was 17.8 months (range 0.4-39.6 months). The mortality rate was 2/18 (11%) patients, including one case of fatal peritonitis, coinciding with protein C concentrate treatment in a 44 day-old, very low birthweight preterm infant and a case of multi-organ failure in a 19 year-old patient. Both deaths were considered not related to protein C concentrate. Ten patients received anticoagulation therapies in addition to protein C including: 4 treatments with antithrombin concentrates, 1 with clopidogrel, 6 with low molecular weight heparin and 7 with unfractionated heparin. Data from historical protein C concentrate treatments which occurred prior to enrollment in the study were collected from 3 patients upon their enrollment into the study (all 3 treatments resulted in halting/reversal of coagulopathy). During the entire study period, 13 adverse events (AEs) were reported in 5 patients with acquired deficiency; among these, 4 were serious adverse events (SAEs). During the period of treatment with protein C concentrate, there were 2 AEs including an SAE of gastroenteritis; neither were considered related AEs. The results of this registry demonstrate that in current clinical practice in the EU, treatment with protein C concentrate was safe with a mortality rate of 11% in patients with acute SAPCD and thrombotic episodes observed in association with sepsis and/or purpura fulminans in this study. Disclosures Knoebl: Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sasse:Baxter/Baxalta/Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding. De Carolis:Baxalta/Baxter: Other: Baxter Investigator for CEPROTIN Registry. Dyck-Jones:Baxter/Baxalta/Shire: Employment, Equity Ownership. Ehrle:Baxter/Baxalta/Shire: Employment, Equity Ownership. Finnerty:Baxalta/Baxter: Employment. Gelmont:Baxter/Baxalta/Shire: Employment, Equity Ownership. Yel:Baxter/Baxalta/Shire: Employment, Equity Ownership. Loghman-Adham:Baxter/Baxalta/Shire: Employment, Equity Ownership. Fischer:Baxter/Baxalta GmBH: Honoraria, Other: 'Weimarer Sepsis Update 2013'; Baxter/Baxalta GmBH: Consultancy, Other: Co-Authorship for E- Book-Preparing (Importance of the Protein C pathway in coagulation disorders and intensive care medicine / Treatment of congenital and acquired protein C deficiency.

This study describes a modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters: A device similar to that used in heart catherisation with a standard micro-introducer serving as sheath and an arterial catheter serving as inner dilator was pushed forward over a wire guide that had before been inserted via a peripheral venous catheter. With this method 2-and 3-French catheters could be safely inserted into peripheral veins of 14 paediatric patients. In conclusion successful insertion of a small peripheral venous catheter offers in most cases a possibility for the placement of a central venous line.

Objectives: In pediatric patients with cardiogenic shock (CS)/or acute cardiac failure (ACF) extracorporeal membrane oxygenation (ECMO) is often used as a bridging procedure to recovery or further implantation of a ventricular assist device (VAD). Although ECMO has been established as a routine procedure in pediatric tertiary care centers, the clinical path guiding these patients to fully recovery or further VAD implantation is one of the most challenging for pediatric intensivists. Methods: The authors describe the use of venoarterial ECMO (VA-ECMO) as a treatment strategy for ACF in spontaneously breathing and conscious pediatric patients. It presents their experiences with the first five children treated using this new concept. The mean age of the patients was 86 months (range 0 – 226 mo). Mean amount of time on ECMO was 35 days (range 7 – 94 d). Results: Three patients fully recovered with their cardiac function while being treated on “Awake-VA-ECMO,” one was bridged to LVAD and one was successfully bridged to transplantation. Four of the five patients are alive without any recurrences. One patient died before a further heart transplantation while being on intracardiac rotation pump. Although reintubation was necessary in three of our five patients (due to interventional heart catheter) total time breathing spontaneously and being conscious while on ECMO was > 70%. Conclusion: The authors conclude that the concept of “Awake VA-ECMO” is feasible and safe for the treatment of ACF and can be used as a “bridging therapy” to recovery or further VAD implantation in pediatric patients.

Background Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. Methods In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. Results The incidence rates of respiratory (−5.06%; 95% CI, −9.52 to −0.59%), renal (−3.87%; 95% CI, −7.58 to −0.15%) and hematologic (−3.89%; 95% CI, −7.26 to −0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. Conclusions In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. Trial registration ClinicalTrials.gov number; NCT00209768

The analysis of the behavior of thermal storage load systems under typical solar conditions may be realized in the laboratory if a heat source is available that behaves like a predifined solar collector. For this purpose a collector hardware simulator (CHS) was built. This CHS allows repetitive experiments with solar storage load systems under variable conditions of temperature and power. The influences of different radiation time patterns, of the collector parameters and of the collector size on the performance of the coupled storage-load system may be studied easily in “quasi-solar” experiments. The description of the CHS includes the analysis of the dynamic behavior of, both, solar collectors and the CHS in the time domain as well as in the frequency domain. The governing differential equations are formulated, and the transfer functions that are obtained by means of Laplace transforms are presented. These transfer functions allow a clear assessment as to which collectors under which conditions can be simulated by a given CHS.

In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the results of these patients, new "bridging-strategies" are necessary. Recent reports demonstrate promising results for the concept of "awake ECMO" in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV-ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5-109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was

Annals of intensive care 2(S1), S8 (2012). doi:10.1186/2110-5820-2-S1-S8 special issue: "Diagnosis and management of intra-abdominal hypertension and abdominal compartment syndrome", Published by Springer, Heidelberg

Purpose To examine the physical properties and chemical composition of particles captured by in-line microfilters in critically ill children, and to investigate the inflammatory and cytotoxic effects of particles on endothelial cells (HUVEC) and macrophages in vitro. Methods Prospective, observational study of microfilters following their use in the pediatric intensive care unit. In vitro model utilizing cytokine assays to investigate the effects of particles on human endothelial cells and murine macrophages. Results Twenty filter membranes from nine patients and five controls were examined by electron microscopy (EM) and energy dispersion spectroscopy (EDX). The average number of particles found on the surface of the used membranes was 550 cm2. EDX analysis confirmed silicon as a major particle constituent. Half of the filter membranes showed conglomerates containing an uncountable number of smaller particles. In vitro, glass particles were used to mimic the high silicon content particles. HUVEC and murine macrophages were exposed to different contents of particles, and cytokine levels were assayed to assess their immune response. Levels of interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha were suppressed. Conclusions Particle contamination of infusion solutions exists despite a stringent infusion regiment. The number and composition of particles depends on the complexity of the applied admixtures. Beyond possible physical effects, the suppression of macrophage and endothelial cell cytokine secretion in vitro suggests that microparticle infusion in vivo may have immune-modulating effects. Further clinical trials are necessary to determine whether particle retention by in-line filtration has an influence on the outcome of intensive care patients. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-1775-y) contains supplementary material, which is available to authorized users.

The objective of this study is to describe and to determine the preclinical situation and early in-clinical situation, diagnostic findings, and factors influencing the outcome of severe head trauma in children. Records of 48 children (0-16 years) were analyzed during a 3-year interval. Correlations with the outcome (Glasgow Outcome Scale) were determined by focusing on different scales, clinical findings, biochemistry, and clinical course features. The initial shock index had a major relevance (P = .0089). Systolic blood pressure (P = .0002) and bradycardia (P = .035) were important factors. Assessing the severity of trauma according to the Glasgow Coma Score, the most accurate parameter for outcome is based on the detailed quality of ‘‘eye opening’’ (P = .0155). Pupillary motoricity at the accident site (P = .002) and emergency room (P = .0004) are strong predictors. Preclinical measurements of stabilization and oxygenation have the same impact as the in-clinical management.

To minimize the secondary brain damage, we analyzed the effect of cerebral perfusion pressure—orientated management and tried to find factors of clinical management and biochemical findings that influence clinical, cognitive, and psychosocial outcome. Management at intensive care unit was standardized. A standardized (short form 36 health survey) and nonstandardized split questionnaire explored long-term outcome. Glutamic-oxaloacetic-transaminase, creatine kinase MB or glucose are markers for bad outcome (P < .05). Patients with cerebral perfusion pressure values below the recommended standard for just a single occurrence had significantly worse outcome (P = .0132). Mean arterial pressure, central venous pressure, and heart rate alone do not correlate with outcome. At least 1 occurrence of mean arterial pressure and central venous pressure below the lower limits resulted in a poor outcome (P = .035). Cerebral perfusion pressure—guided therapy seems to prevent further brain damage and results in outcome scores that are comparable to those children with head trauma exhibiting symptoms of mild brain edema.

Hypoplastic left heart syndrome (HLHS) encompasses a broad spectrum of congenital cardiac anomalies. It is characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle, including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch.1 A 25-year-old woman gave birth to her first child in the 40th week of gestation via caesarean delivery because of a pathological cardiotocogram. The neonate was transferred to the pediatric intensive care unit. Although the chest x-ray was unsuspicious on the first day of life (Figure 1A), the ECG exhibited ST elevation in left precordial leads indicating myocardial damage (Figure 1B), an unusual finding even in HLHS. Echocardiography confirmed the already prenatally diagnosed HLHS with aortic atresia and severe mitral hypoplasia (Figure 2A; online-only Data Supplement Movie I). The most interesting and critical finding was the presence of several marked myocardial sinusoids in the thickened left ventricular myocardium (Figure 2B and 2C; online-only Data Supplement Movies II and III). To clarify the anatomy, cardiac catheterization and angiography were performed. HLHS with aortic atresia and an extreme hypoplastic mitral valve with trivial incompetence and a small left ventricle with suprasystemic blood pressure were confirmed (Figure 3A; online-only Data Supplement Movie IV). …

In July, 2003, during reinduction treatment 5 months after diagnosis of acute lymphoblastic leukaemia (ALL), a 4-yearold girl presented with generalised tonic-clonic seizures. She had been treated according to protocol ALL-BFM 2000. Cranial CT and analysis of cerebrospinal fl uid showed no signs of cerebral haemorrhage. Ultra sonography showed an enlarged liver and no signs of ascites or veno-occlusive disease. Her skin appeared normal, with no vesicular rashes. Blood tests showed only raised concentrations of aminotransferases. During the next few hours, she developed respiratory insuffi ciency, petechiae, haematomas, and vesicular lesions of the oral and vagi nal mucosal. On the assumption of an underlying infec tious cause, intravenous treatment with piperacillin, sulbactam, tobramycin, IgG, and aciclovir was initiated. 48 h after the fi rst seizure, her laboratory test results deteriorated, with aspartate and alanine aminotransferase concentrations increasing to 20 864 U/L and 16 029 U/L, respectively, and the full blood cell count indicated pancytopenia. Within 12 h, she developed multi-organ failure (liver, renal, and circulatory failure, and acute respiratory distress syndrome [ARDS]), necessitating artifi cial ventilation. Serostatus for varicella-zoster virus (VZV) was negative, but PCR for VZV was positive in peripheral blood samples (7×106 genome copies per mL). VZV was also isolated from a nasopharyngeal swab but not from cerebrospinal fl uid. PCR analysis of peripheral blood was negative for hepatitis B and C viruses, herpes simplex virus 1 and 2, Epstein-Barr virus, cytomegalovirus, adenovirus, enterovirus, human herpes virus 6, and parvovirus B19. High doses of VZVIgG were added to the treatment. Despite haemo dialysis and ventilation, the child died of progressive ARDS and multi-organ failure 10 days after admission. On receiving the positive VZV-PCR results, the mother recalled that her daughter had received live attenuated VZV vaccine (Varilrix) at another hospital 32 days before the onset of symptoms. Partial sequencing of VZV genes 38 and 54 isolated from the patient excluded a wild-type VZV infection and showed that viraemia was caused by the VZV vaccine strain OKA (fi gure). Vaccination was done 5 months after complete remission had been achieved; at that time lymphocyte count was more than 1·5×109/L, and chemotherapy was interrupted for 1 week before and after vaccination. Deaths after vaccinations with numerous attenuated viruses are well established. Fatal wild-type VZV infections have been reported in ALL patients during chemotherapy and after bone-marrow cell transplantation. Therefore, VZV vaccination is a useful, and generally accepted, therapeutic measure for patients with ALL in remission. Studies of VZV vaccination 3–4 months after autologous stem-cell transplantation, and in early ALL maintenance therapy, did not show fatal side-eff ects. However, any interruption of maintenance therapy in ALL can adversely aff ect outcome for the patient. In our patient, liver failure developed 5 weeks after VZV vaccination, which indicates longstanding replication of OKA strain in the liver. This suggestion accords with observations of late onset of complications (fever, vesicles, and severe hepatitis) in immunocompromised patients after VZV vaccination. Therefore, although we cannot fully exclude that intensifi cation of chemotherapy could have aggravated her symptoms, we suggest that VZV vaccination in seronegative children with leukaemia, who are in complete remission for at least 12 months, should not be undertaken until at least 9 months after the end of immunosuppressive treatment (including maintenance therapy) and not before a lymphocyte count of at least 1·5×109/L has been ascertained. In addition, high-risk patients should remain under close surveillance in the critical phase (6 weeks after vaccination) so that immediate antiviral treatment with aciclovir can be initiated in symptomatic children.

Torsades de points (Tdp) is a form of ventricular tachycardia, and its occurrence in childhood is very rare. In adult patients treated with sotalol, Tdp has been reported to the occur with an incidence of 2%-4%. In children who are treated with sotalol, occurrence of Tdp has been reported in only a single case. A 15-month-old girl with Wolff-Parkinson-White syndrome developed recurrent syncopal attacks. She had been treated with sotalol 1.5 mg/kg daily since shortly after birth because of recurrent episodes of paroxysmal supraventricular tachycardia. ECG monitoring exhibited frequent Tdp tachycardia. Serum electrolyte levels were normal. Echocardiographic analysis excluded a structural heart defect and did not show any signs of myocardial infection. Sotalol treatment was stopped and an infusion with lidocaine was started. Despite this therapy the Tdp continued. Magnesium aspartate was then administered, which immediately stopped the Tdp. As no other reason was evident, Tdp in this child has to be judged as a proarrhythmia related to sotalol therapy.

Looking at the potential benefit of in-line filtration in reducing major complications occurring during intensive care unit stay, we would like to present the electron microscopy analysis of a filter used in a 17-year-old girl after aortic valve replacement. The patient received all drugs and fluids through a Pall Posidyne NEO filter with …

A 4 1/2-year-old girl with a so far unremarkable medical history became comatose during a simple infection. She showed severe metabolic acidosis without elevation of lactate. In blood the branched-chain amino acids were increased. In urine ketone-bodies, increased 3-OH-isovaleric and 3-OH propionic acid excretion were detected, while methylmalonate was not found. The profile of acylcarnitines revealed increased propionylcarnitine. Despite restriction of protein supply, high-caloric nutrition, correction of acidosis, and supplementation of biotin and carnitine, the girl died 2 days after admission due to arrhythmia of the heart. In skin fibroblasts the activity of propionyl—coenzyme A carboxylase (PCC) was markedly decreased. Mutation analysis confirmed the diagnosis of propionic acidemia (PA) with compound heterozygosity for 2 new missense mutations L417W/Q293E in the PCCA gene, with the mother carrying the Q293E and the father the L417W mutation. Late-onset PA should be included in the differential diagnosis of unclear coma. Determination of the acylcarnitines using tandem mass spectrometry as well as organic acids in urine is recommended.

Background Some paediatricians seem to take Intra-abdominal Hypertension (IAH) and Abdominal Compartment Syndrome (ACS) for epiphenomenons of disorders which exclusively accompany illnesses that are treated only in specialised centres. Since the majority of ACS results from inflammation and capillary leakage, also disorders can lead to IAH/ACS, which superficially seem to be harmless paediatric entities. Thereby, the majority of IAH/ACS might be overseen and not be treated adequately. Aims The present study looks at the recognition and knowledge of IAH/ACS among paediatric intensivists of different sizes of ICU´s and number of cases per year. Methods In June 2010, a questionnaire was mailed to the heads of ICU´s of 265 German, Austrian and Swiss paediatric hospitals. Results Response rate was 59%. The more specialised departments are, the more often IAH/ACS is diagnosed. Predominantly, small ICU (s-ICU; 700 pat./a) at least diagnosed one case of IAH; >40% at least one ACS (s-ICU: 16% and 13%). Prevalence of IAH/ACS at intermediate ICU´s (i-ICU; 350–700 pat./a) and l-ICU´s was stated to be more than twice as high. Stated underlying risk factors only marginally varied between s-ICU´s, i-ICU´s and l-ICU´s. Regular IAP-measurements are performed by 13% of s-ICU´s in contrast to 20% and 35% of larger ones. Main reason is the lack of equipment. At least one decompressive laparotomy was performed by 41% of l-ICU´s in contrast to 7% of s-ICU´s. Conclusions Definitions and guidelines regarding diagnosis and management of IAH/ACS are not applied uniformly. This variability could express an ever present lack of awareness and solid prospective data.

Critical care 16(1), R16 (2012). doi:10.1186/cc11161, Published by BioMed Central Ltd, London

Objectives: Sepsis, systemic inflammatory response syndrome (SIRS) or organ failure often complicate the clinical course on intensive care units. Particulate contamination of infusion solution may contribute to clinical deterioration of these patients. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. In-line filtration almost completely prevents particulate infusion. We assessed the effect of in-line filtration on reduction of major complications in critically ill children (Clinical Trials.gov ID NCT 00209768). Patients and Methods: In a randomised, prospective trial children admitted to interdisciplinary PICU of tertiary university hospital were assigned to either control or interventional group, the latter receiving in-line filtration (infusion filter Pall ELD96LLCE/NOE96E, Braun Intrapur Lipid/ Intrapur Neonat Lipid) throughout infusion therapy. Prior to this study, infusion regiment was optimised to prevent precipitation and incompatibilities of solutions and drugs. Primary objectives included a reduction in incidence of sepsis, thrombosis, systemic inflammatory response syndrome (SIRS), organ failure (liver, lung, kidney, circulation) and mortality. Results: 807 children (343 female, 464 male) with heterogeneous background of underlying diagnoses and Gaussian distribution to either control or in-line filtration group were included. According to study criteria a significant reduction in incidence of SIRS for interventional group (95% CI, 145 versus 200 patients, P< 0.001) was evident. No differences were demonstrated for occurrence of sepsis, thrombosis, organ failure (liver, lung, kidney, circulation) or mortality between both groups. Conclusion: SIRS often complicates treatment in intensive care medicine. Inline-filtration is most effective reducing the incidence of SIRS and offers a novel therapeutic option.

Objectives: Recently introduced paediatric cardiac output monitor (COstatus, Transonic Systems Inc. Ithaca, NY) also measures blood volumes and detects cardiac shunts. The current study assessed its ability to identify left-to-right shunts and measured associated blood volumes during cardiac catheterisation in children. Patients and Methods: Cardiac catheterisation was performed in 20 children and adolescents (3.5 kg- 102 kg). Shunts and pulmonary (Qp) versus systemic blood flow (Qs) ratio were determined by routine oximetry. Subsequently three measurements with COstatus were performed while the monitor software announces the recognition of left-to-right shunt. Dilutions curves were recorded and validated. Results: Left-to-right shunts due to various types of cardiac defects were detected in 6 patients by oximetry. Applying COstatus diagnostic accuracy was very convincing, with a sensitivity of 100% (6/6) and a specificity of 92.8% (13/14). The threshold for determination a left-to-right shunt was an Qp/Qs ratio of 1.3. In one case of a hypertrophic obstructive cardiomyopathy the distortion of the dilution curve led to a false positive result. A significant difference was detected for means of central blood volume index between patients with left-to-right shunts and controls with no cardiac shunts (95% CI; 24.9 versus 18.2 ml/kg; P< 0.05). Conclusion: Novel ultrasound dilution technique identifies left-to-right shunts in children with a high sensitivity and detects even small shunts with an Qp/Qs ratio of 1.3. Raised central blood volume index corresponds well with clinical features in patients with left-to-right shunts and may become helpful a diagnostic parameter in the future.

Introduction: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods: In Germany, patients receiving protein C concentrate (Ceprotin(R), Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this National, retrospective, multi-centered study. Results: Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions: This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.

Sepsis, systemic inflammatory response syndrome (SIRS) or organ failure often complicate the clinical course on an ICU. Particulate contamination of the infusion solution may contribute to the clinical deterioration of these patients. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. The use of inline filtration with microfilters almost completely prevents particulate infusion. We assessed the effect of inline filtration on the reduction of major complications in critically ill children (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768).

Particulate contamination of infusion solution implies a potential health risk for intensive care patients with a background of debilitation and impaired host responses. Particles have been shown to induce thrombogenesis, deterioration of microcirculation and modulation of immunoresponse. We assessed the effect of inline filtration on the reduction of major complications in critically ill children (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768).

As a part of a clinical trial to evaluate the potential benefits of inline filtration on reducing major complications of paediatric ICU (PICU) patients (Clinical Trials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT 00209768","term_id":"NCT00209768"}}NCT 00209768), we examined the physical aspects and chemical composition of particles captured by inline microfilters. Additionally we investigated the inflammatory and cytotoxic effects of particles on human endothelial cells and macrophages in vitro.

Human protein C (PC) concentrate may anticipate thrombotic microangiopathy and facilitate fibrinolysis in the severe hemolytic uremic syndrome (HUS). We report the effects of PC in six HUS patients. HUS is characterized by a simultaneous occurrence of hemolytic anemia, thrombocytopenia and acute renal failure. Postdiarrheal HUS is often based on an infection with EHEC producing Shiga toxins. Our current pathogenetic understanding is that Shiga toxins cause endothelial injury, leading to thrombotic microangiopathy. There is still a 5% rate of mortality particularly caused by cerebral involvement.