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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.

Background Despite the suggestion that the inflammatory response in traumatized children is functionally unique, prognostic markers predicting pediatric multiple organ failure are lacking. We intended to verify whether Interleukin-6 (IL-6) displays a pivotal role in pediatric trauma similar to adults. Methods Traumatized children less than 18 years of age with an Injury Severity Score >9 points and consecutive admission to the hospital’s pediatric intensive care unit were included. Organ function was evaluated according to the score by Marshall et al. while IL-6 levels were measured repetitively every morning. Results 59 traumatized children were included (8.4 ± 4.4 years; 57.6% male gender). Incidence of MODS was 11.9%. No differences were found referring to age, gender, injury distribution or overall injury severity between children with and without MODS. Increased IL-6 levels during hospital admission were associated with injury severity (Spearman correlation: r = 0.522, p