Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family.

Tidal volume drives inflammation during mechanical ventilation for viral respiratory infection.

OBJECTIVE: Respiratory syncytial virus lower respiratory tract infection is the most frequent cause of respiratory insufficiency necessitating mechanical ventilation in infants during the winter season. Recently, we presented a new animal model to show that mechanical ventilation aggravates respiratory syncytial virus-induced pulmonary inflammation by distinct mechanisms. We now use this model to study whether low tidal volume mechanical ventilation causes less ventilator-induced lung injury in the presence of respiratory syncytial virus lower respiratory tract infection. DESIGN: Randomized controlled experimental study. SETTING: University Medical Center animal laboratory. SUBJECTS: Male BALB/c mice, 6-8 weeks old and weighing 20-28 g. INTERVENTIONS: Mice were inoculated with respiratory syncytial virus or mock virus on day 0 and ventilated on day 1 or 5 with high (12 mL/kg) or low (6 mL/kg) tidal volume for 5 hours. MEASUREMENTS AND MAIN RESULTS: Total and differential cell counts as well as cytokine concentrations were determined in bronchoalveolar lavage fluid. Compared with nonventilated respiratory syncytial virus-infected mice, high tidal volume ventilation of respiratory syncytial virus-infected mice on day 5 enhanced bronchoalveolar lavage fluid total cell count (0.35 vs 0.99 × 10e6/mL; p < 0.01), neutrophils (0.02 vs 0.17 × 10e6/mL; p < 0.01), interleukin-6 (58 vs 250 pg/mL; p < 0.01), and keratinocyte-derived chemokine (95 vs 335 pg/mL; p < 0.01) levels. In low tidal volume ventilation of respiratory syncytial virus-infected mice, no significant difference in cell counts or cytokine concentrations was observed compared with spontaneous breathing respiratory syncytial virus-infected controls on both days. CONCLUSIONS: Low tidal volume mechanical ventilation causes less ventilation-induced cellular and cytokine influx into the bronchoalveolar space during respiratory syncytial virus lower respiratory tract infection.

Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs. PATIENTS: Children with meningococcal sepsis. INTERVENTION: Skin biopsy and blood sample collection. MEASUREMENTS AND MAIN RESULTS: Determination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = -0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037). CONCLUSIONS: Microvascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.

FOXP3+ CD4+ Tregs lose suppressive potential but remain anergic during transient inflammation in human.

Tregs are crucial in controlling inflammation. Although the transcription factor FOXP3 is the most applicable phenotype marker of Tregs, it does not indisputably characterize suppressive function during T-cell activation in vitro. A question that remains is: what is the functionality of FOXP3(+) T cells during inflammation in vivo? We studied FOXP3(+) T cells in a human model of acute inflammation due to cardiac surgery. Twenty-five children who underwent cardiac surgery for correction of a septum defect were included. Following surgery, we observed a transient systemic inflammatory response accompanied by an increased proportion of CD25(bright) T cells with sustained Treg phenotype. During this transient immune activation, both the percentage of CD4(+) FOXP3(+) cells and the level of expression of FOXP3 in the CD4(+) CD25(bright) CD127(low) population increased. While Tregs remained present during systemic inflammation and continued to be anergic, the capacity to suppress effector T cells was reduced. The reduced suppressive state of Tregs could be induced in vitro by plasma obtained during the peak of inflammation after surgery. These data show that inflammation inhibits Treg function through soluble factors present in plasma. These results underscore the functional role of FOXP3(+) Tregs during inflammation in vivo.

Host response to mechanical ventilation for viral respiratory tract infection.

Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection. Furthermore, the response to induced hypercapnic acidosis, reported to dampen the inflammatory response to mechanical ventilation in non-infectious models, was assessed. BALB/c mice were inoculated with RSV or mock-suspension and ventilated for 5 h on day 5 post inoculation. Mechanical ventilation of infected mice resulted in enhanced cellular influx and increased concentrations of pro-inflammatory cytokines in the bronchoalveolar space. Microarray analysis showed that enhanced inflammation was associated with a molecular signature of a stress response to mechanical ventilation with little effect on the virus-induced innate immune response. Hypercapnic acidosis during mechanical ventilation of infected mice did not change host transcript profiles. We conclude that mechanical ventilation during RSV infection adds a robust but distinct molecular stress response to virus-induced innate immunity activation, emphasising the importance of lung-protective mechanical ventilation strategies. Induced hypercapnic acidosis has no major effect on host transcription profiles during mechanical ventilation for RSV infection, suggesting that this is a safe approach to minimise ventilator-induced lung injury.

Mechanical ventilation for respiratory failure in children with severe neurological impairment: is it futile medical treatment?

AIM: To assess outcome for children with severe neurological impairment receiving invasive mechanical ventilation for respiratory failure. METHOD: Medical charts for all such children treated in our intensive care unit (ICU) between January 2003 and July 2008 were reviewed. Outcomes were compared with those for children with moderate neurological impairment. RESULTS: Twenty-two children with severe neurological impairment were included (nine females, 13 males; median age 7y 10mo; range 4mo-17y). The median duration of mechanical ventilation was 16 days. Six children had an uneventful 1-year survival, the others required reintubation or readmission to the ICU, or died. Eleven children were still alive 1 year after discharge from the ICU. Nine patients died of respiratory failure. None of the children in the severe group died of a heart defect. Eleven children with moderate neurological impairment were included (eight females, three males; median age 1y 1mo, range 4mo-13y). Four children had an uneventful 1-year survival. Eight children were still alive 1 year after discharge from the ICU. Two of the three non-survivors died of their heart defects. INTERPRETATION: Mechanical ventilation for respiratory failure in children with severe neurological impairment is complex and associated with limited survival. However, it cannot be regarded as futile medical treatment. Further studies are urgently needed for the rational guidance of clinical decision-making.

Ventilator-induced endothelial activation and inflammation in the lung and distal organs.

INTRODUCTION: Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung. METHODS: Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours. To study the effects of alveolar stretch in vivo, we applied a MV strategy that causes overstretch of pulmonary tissue i.e. 20 cmH2O peak inspiratory pressure (PIP) and 0 cmH2O positive end expiratory pressure (PEEP). Non-ventilated, sham-operated animals served as a reference group (non-ventilated controls, NVC). RESULTS: Alveolar stretch imposed by MV did not only induce de novo synthesis of adhesion molecules in the lung but also in organs distal to the lung, like liver and kidney. No activation was observed in the brain. In addition, we demonstrated elevated cytokine and chemokine expression in pulmonary, hepatic and renal tissue after MV which was accompanied by enhanced recruitment of granulocytes to these organs. CONCLUSIONS: Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.

Changes in infectious disease mortality among children in the Netherlands.

In this study we examine the changes in mortality due to infectious diseases in childhood over recent decades. We analysed mortality data among children due to infectious diseases from 1969 until 2006. This study shows a steep decline of infectious disease mortality in the 1970s, followed by a relative stabilisation thereafter. This was caused by an isolated decline in infectious disease mortality in children younger than 5 years. In children over 5 years of age the infectious disease mortality remained stable during the entire study period. Analysis of mortality data of our paediatric intensive care unit (PICU) shows an increasing trend in mortality due to infections in children with underlying illnesses. Infections in childhood have remained a stable burden of mortality over recent decades.

Life-threatening human herpes virus-6 infection in early childhood: presenting symptom of a primary immunodeficiency?

OBJECTIVE: To report two previously healthy children with a life-threatening course of human herpes virus type 6 (HHV-6) infection and prolonged pediatric intensive care treatment. DESIGN: Case reports. SETTING: A 16 bed pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Two children with life-threatening HHV-6 disease. INTERVENTIONS: Both children were mechanically ventilated because of respiratory failure. A detailed viral and immunologic workup was performed and treatment with antiviral medication started. MEASUREMENTS: Polymerase chain reaction assays of plasma, cerebrospinal fluid, bronchoalveolar lavage, and lung biopsies yielded HHV-6 in both patients. Immunophenotyping and lymphocyte stimulation tests with both mitogens and antigens indicated an immunodeficiency in both patients. CONCLUSION: HHV-6 infection should be considered in infants and young children with respiratory failure or meningo-encephalitis without clear causative agent or failure to respond to empirical treatment. A thorough immunologic workup and early start with antiviral therapy in any patient with a life-threatening course of HHV-6 infection is mandatory, because a severe HHV-6 infection can be the first indication of a primary immunodeficiency.

Survival in a recent cohort of mechanically ventilated pediatric allogeneic hematopoietic stem cell transplantation recipients.

There is ongoing discussion whether survival improved for children requiring mechanical ventilation after hematopoietic stem cell transplantation (HSCT). We reviewed the outcomes of 150 children who received an allogeneic HSCT between January 1999 and April 2007, in a pediatric university hospital in The Netherlands. Thirty-five of the 150 patients received mechanical ventilation on 38 occasions. None of the recorded risk factors was significantly associated with the requirement of mechanical ventilation. Sixteen admissions resulted in death in the intensive care unit (ICU), giving a case fatality rate of 42% (95% confidence interval 26%-58%). ICU mortality was associated with multiorgan failure on the second day of admission and with the use of high frequency oscillatory ventilation. Patients had higher pediatric risk of mortality scores than in previous studies, reflecting higher acuity of illness on admission to the ICU. Six-month survival in patients discharged from the ICU was 82%. Compared to previous studies, we found an improvement in ICU survival and survival 6 months after ICU discharge in a recent cohort of ventilated children after allogeneic HSCT, even though our patients were more severely ill. Our results are promising, but they need to be confirmed in larger, preferably multicenter, studies.

Intensive care unit mortality trends in children after hematopoietic stem cell transplantation: a meta-regression analysis.

BACKGROUND: There is ongoing discussion whether intensive care unit mortality has decreased over time for children after hematopoietic stem cell transplantation. OBJECTIVE: To analyze intensive care unit mortality trends in children after hematopoietic stem cell transplantation. DATA SOURCES: Search of MEDLINE, EMBASE, and Cochrane databases, and a manual review of reference lists. STUDY SELECTION: Prospective and retrospective cohort studies containing intensive care unit mortality data of children after hematopoietic stem cell transplantation. DATA EXTRACTION: Mortality statistics and features associated with mortality were abstracted from studies of interest. To assess mortality over time, the median years of inclusion in original studies were included as risk factor. A multiple random-effects meta-regression analysis was conducted to assess the independent contribution of prognostic factors on mortality. DATA SYNTHESIS: Twenty-three studies were included, reporting on 1101 intensive care unit admissions. Overall intensive care unit mortality was 60% (range, 25%-91%). Once mechanical ventilation was necessary (n = 822), mean intensive care unit mortality was 71% (range, 25%-91%). Over the years, significantly fewer intensive care unit admitted patients received mechanical ventilation (p < 0.001). Univariable analysis in all intensive care unit admitted patients showed a significant decrease in mortality associated with year of inclusion. Mechanical ventilation and pulmonary disease were associated with increased mortality. In the multiple meta-regression analysis, only pulmonary disease remained significantly associated with mortality (odds ratio = 1.21, 95% confidence interval 1.01-1.46 per 10% increase in the number of patients with pulmonary disease in studies). The association between year of inclusion and intensive care unit mortality was less pronounced (odds ratio = 0.92, 95% confidence interval 0.84-1.01). CONCLUSION: There is a widely held impression that intensive care unit mortality clearly decreased in children after hematopoietic stem cell transplantation. However, characteristics of intensive care unit admitted patients significantly changed over time. After correcting for this, an improvement in intensive care unit survival was less evident. More studies are needed before a true improvement in intensive care unit survival can be confirmed.

Improving outcome in meningococcal disease: don't forget compartment syndrome!

OBJECTIVE: To advocate a surgical intervention that can prevent the loss of limbs in patients with meningococcal disease. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 4-month-old male infant presenting with acute circulatory failure due to meningococcal disease. INTERVENTIONS: Measurements of compartment pressures of all extremities and echo-Doppler of peripheral arteries were performed at regular intervals, starting at admittance to the pediatric intensive care unit. After compartment syndrome in the lower extremities was diagnosed, emergency surgical intervention (fasciotomy and arteriolysis) was performed in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: During surgery, the compartments initially revealed pale, poorly perfused tissue. After decompression, immediate bulging of the muscles and restoration of microcirculation were seen. All digits were spared, and muscle compartments remained vital with exception of the tibialis anterior and extensor hallucis longus muscles in the left leg. Several ecchymoses and purpura of the lower extremities caused skin necrosis, necessitating skin transplants. No other surgical intervention was required. CONCLUSIONS: In meningococcal disease, compartment syndrome can occur within hours after initial presentation due to massive capillary leakage and circulatory failure. Immediate surgical intervention is the gold standard in treatment, making early recognition vital. In all patients presenting with meningococcal disease, compartment syndrome should be considered and early monitoring included in the initial evaluation.

Meta-regression analysis of high-frequency ventilation vs conventional ventilation in infant respiratory distress syndrome.

OBJECTIVE: There is considerable heterogeneity among randomized trials comparing high-frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in premature neonates with respiratory distress syndrome. We investigated what factors explained differences in outcome among these trials. DESIGN: Meta-regression analysis of 15 randomized trials. MEASUREMENTS AND RESULTS: Variables were extracted to explain heterogeneity: year of publication; use of Sensormedics 3100A ventilator for HFV; time on CMV prior to start of study; gestational age; use of surfactant; high lung volume strategy in HFV; and lung protective ventilation strategy in CMV and baseline risk. Chronic lung disease (CLD) and death or CLD were outcome measures. Relative risk ratios were calculated to estimate effect sizes of explanatory variables on reported relative risks. Adjusted estimates of relative risk ratios of high lung volume strategy and lung protective ventilation strategy were 0.42 (95% CI 0.06-2.48) and 2.02 (95% CI 0.18-23.12) for CLD, respectively. The effect of gestational age was less pronounced (RRR=1.17 (95% CI 0.16-8.32) for CLD, respectively). Use of Sensormedics and prior time on CMV had the smallest effects [RRR=0.96 (95% CI 0.47-1.94) and RRR=0.85 (95% CI 0.58-1.24) for CLD, respectively)]. The same results applied to CLD or death as outcome. CONCLUSIONS: Variation in ventilation strategies that were used in trials comparing HFV with CMV in premature neonates offered the most likely explanation for the observed differences in the outcome of these trials compared with other explanatory factors.

Two cases of fatal meningitis due to Fusobacterium necrophorum.

It is extremely important to consider Fusobacterium necrophorum as a cause of meningitis in children after otitis or other upper respiratory tract infections, because of its increasing incidence. A high index of suspicion and prompt microbiological identification are mandatory; as this organism is often penicillin-resistant, prolonged antibiotic therapy is required and invasive infection carries a high risk of fatal cerebral vessel thrombosis. This report presents two fatal cases who presented to our pediatric intensive care unit in December 2004.

Transcranial Doppler ultrasonography to confirm brain death: a meta-analysis.

OBJECTIVE: Barbiturate therapy or hypothermia precludes proper diagnosis of brain death either clinically or by EEG. Specific intracranial flow patterns indicating cerebral circulatory arrest (CCA) can be visualized by transcranial Doppler ultrasonography (TCD). The aim of this study was to assess the validity of TCD in confirming brain death. DESIGN: Meta-analysis of studies assessing the validity of TCD in confirming brain death. METHODS: A systematic review of articles in English on the diagnosis brain death by TCD, published between 1980 and 2004, was performed. An oscillating or reverberating flow and systolic spikes were considered to be compatible with CCA. The quality of each study was assessed using standardized methodological criteria. The literature was searched for any article reporting a false-positive result. RESULTS: Two high-quality and eight low-quality studies were included. Meta-analysis of the two high-quality studies showed a sensitivity of 95% (95% CI 92-97%) and a specificity of 99% (95% CI 97-100%) to detect brain death. Meta-analysis of all ten studies showed a sensitivity of 89% and a specificity of 99%. In the literature we found two false-positive results; however, in both patients brain-stem function did show brain death shortly thereafter. CONCLUSIONS: CCA by TCD in the anterior and posterior circulation predicted fatal brain damage in all patients; therefore, TCD can be used to determine the appropriate moment for angiography. Further research is needed to demonstrate that CCA by TCD on repeated examination can also predict brain death in all patients.

Systematic review of determinants of mortality in high frequency oscillatory ventilation in acute respiratory distress syndrome.

INTRODUCTION: Mechanical ventilation has been shown to cause lung injury and to have a significant impact on mortality in acute respiratory distress syndrome. Theoretically, high frequency oscillatory ventilation seems an ideal lung protective ventilation mode. This review evaluates determinants of mortality during use of high frequency oscillatory ventilation. METHODS: PubMed was searched for literature reporting randomized trials and cohort studies of high frequency ventilation in adult patients with acute respiratory distress syndrome. Data on mortality and determinants were extracted for patients treated with high frequency oscillatory ventilation. Linear regression analyses were conducted to produce graphical representations of adjusted effects of determinants of mortality. RESULTS: Cohorts of patients treated with high frequency oscillatory ventilation from two randomized trials and seven observational studies were included. Data from cohorts comparing survivors with non-survivors showed differences in age (42.3 versus 51.2 years), prior time on conventional mechanical ventilation (4.0 versus 6.2 days), APACHE II score (22.4 versus 26.1), pH (7.33 versus 7.26) and oxygenation index (26 versus 34). Each extra day on conventional ventilation was associated with a 20% higher mortality adjusted for age and APACHE II score (relative risk (RR) 1.20, 95% confidence interval (CI) 1.15-1.25). However, this association was confounded by differences in pH (pH adjusted RR 1.03, 95% CI 0.73-1.46). Oxygenation index seemed to have an independent effect on mortality (RR 1.10, 95% CI 0.95-1.28). CONCLUSION: Prolonged ventilation on conventional mechanical ventilation prior to high frequency oscillatory ventilation was not related to mortality. Oxygenation index was a determinant of mortality independent of other disease severity markers.

Breath-to-breath analysis of abdominal and rib cage motion in surfactant-depleted piglets during high-frequency oscillatory ventilation.

OBJECTIVE: To assess the value of monitoring abdominal and rib cage tidal displacement as an indicator of optimal mean airway pressure (Paw) during high-frequency oscillatory ventilation (HFOV). DESIGN AND SETTING: Prospective observational study in a university research laboratory. ANIMALS: Eight piglets weighing 12.0+/-0.5 kg, surfactant depleted by lung lavage. INTERVENTIONS: Compliance of the respiratory system (C(rs)) was calculated from a quasistatic pressure volume loop. After initiation of HFOV lung volume was recruited by increasing Paw to 40 cmH(2)O. Then mean Paw was decreased in steps until PaO(2)/FIO(2) was below 100 mmHg. Proximal pressure amplitude remained constant. MEASUREMENTS AND RESULTS: Abdominal and rib cage tidal displacement was determined using respiratory inductive plethysmography. During HFOV there was maximum in tidal volume (Vt) in seven of eight piglets. At maximal mean Paw abdominal and rib cage displacement were in phase. Phase difference between abdominal and rib cage displacement increased to a maximum of 178+/-28 degrees at minimum mean Paw. A minimum in abdominal displacement and a maximum of Vt was found near the optimal mean Paw, defined as the lowest mean Paw where shunt fraction is below 0.1. CONCLUSIONS: During HFOV abdominal and rib cage displacement displayed mean Paw dependent asynchrony. Maximal Vt and minimal abdominal displacement coincided with optimal C(rs), oxygenation, and ventilation, suggesting potential clinical relevance of monitoring Vt and abdominal displacement during HFOV.

Concurrent bacterial infection and prolonged mechanical ventilation in infants with respiratory syncytial virus lower respiratory tract disease.

OBJECTIVE: To identify demographic, clinical, and laboratory variables predictive for a concurrent bacterial pulmonary infection in ventilated infants with respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) and investigate antimicrobial drug use. DESIGN AND SETTING: Retrospective, observational study in a 14-bed pediatric intensive care unit. PATIENTS: 82 infants younger than 1 year of age with a virologically confirmed RSV LRTD during 1996-2001, of whom 65 were mechanically ventilated. RESULTS: Microbiological data were available from 38 ventilated infants, 10 of whom had a positive blood culture (n=1) or endotracheal aspirate (n=9) obtained upon admission to the pediatric intensive care unit (PICU). Infants with a positive culture had a lower mean gestational age but were otherwise demographically comparable to those with negative culture results. Infants with a positive culture were ventilated 4 days longer. Indicators for a concurrent bacterial infection were comparable between ventilated and nonventilated infants. Antimicrobial drugs were used in 95.1% of infants (100% of ventilated infants) with a mean duration of 7.8+/-0.3 days. The moment of initiation and duration of antimicrobial drug treatment varied considerably. CONCLUSIONS: We observed in ventilated infants a low occurrence of concurrent bacterial pulmonary infection, but infants with positive cultures needed prolonged ventilatory support. Improvement in the diagnosis of a pulmonary bacterial infection is warranted to reduce the overuse of antimicrobial drugs among ventilated infants with RSV LRTD and to restrict these drugs to the proper patients.

High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].

INTRODUCTION: To compare the safety and efficacy of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CV) for early intervention in adult respiratory distress syndrome (ARDS), a multi-centre randomized trial in four intensive care units was conducted. METHODS: Patients with ARDS were randomized to receive either HFOV or CV. In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures. CV ventilation strategy was aimed at reducing tidal volumes. In the HFOV group, an open lung strategy was used. Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up. RESULTS: The study was prematurely stopped. Thirty-seven patients received HFOV and 24 patients CV (average APACHE II score 21 and 20, oxygenation index 25 and 18 and duration of mechanical ventilation prior to randomization 2.1 and 1.5 days, respectively). There were no statistically significant differences in survival without supplemental oxygen or on ventilator, mortality, therapy failure, or crossover. Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 (95% CI 0.22-2.97) for survival without oxygen or on ventilator, and an odds ratio for mortality of 1.15 (95% CI 0.43-3.10) for HFOV compared with CV. The response of the oxygenation index (OI) to treatment did not differentiate between survival and death. In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day. A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI. CONCLUSION: No significant differences were observed, but this trial only had power to detect major differences in survival without oxygen or on ventilator. In patients with ARDS and higher baseline OI, however, there might be a treatment benefit of HFOV over CV. More research is needed to establish the efficacy of HFOV in the treatment of ARDS. We suggest that future studies are designed to allow for informative analysis in patients with higher OI.

Invasive group A streptococcal infection after tonsillectomy.

Tonsillectomy is a very common procedure in childhood. Infectious complications after tonsillectomy are infrequently reported. We describe two children with severe group A beta-hemolytic streptococcal infection after tonsillectomy, and we review the literature about bacteremia and infectious complications after tonsillectomy.