Eliane Roseli Barreira

Epidemiology and outcomes of acute respiratory distress syndrome in children according to the Berlin definition: a multicenter prospective study.

Objectives: In 2012, a new acute respiratory distress syndrome definition was proposed for adult patients. It was later validated for infants and toddlers. Our objective was to evaluate the prevalence, outcomes, and risk factors associated with acute respiratory distress syndrome in children up to 15 years according to the Berlin definition. Design: A prospective, multicenter observational study from March to September 2013. Setting: Seventy-seven PICU beds in eight centers: two private hospitals and six public academic hospitals in Brazil. Patients: All children aged 1 month to 15 years admitted to the participating PICUs in the study period. Interventions: None. Measurements and Main Results: All children admitted to the PICUs were daily evaluated for the presence of acute respiratory distress syndrome according to the American-European Consensus Conference and Berlin definitions. Of the 562 patients included, acute respiratory distress syndrome developed in 57 patients (10%) and 58 patients (10.3%) according to the Berlin definition and the American-European Consensus Conference definition, respectively. Among patients with acute respiratory distress syndrome according to the Berlin definition, nine patients (16%) were mild, 21 (37%) were moderate, and 27 (47%) were severe. Compared with patients without acute respiratory distress syndrome, patients with acute respiratory distress syndrome had significantly higher severity scores, longer PICU and hospital length of stay, longer duration of mechanical ventilation, and higher mortality (p < 0.001). The presence of two or more comorbidities and admission for medical reasons were associated with development of acute respiratory distress syndrome. Comparisons across the three the Berlin categories showed significant differences in the number of ventilator-free days (21, 20, and 5 d, p = 0.001) and mortality for severe acute respiratory distress syndrome (41%) in comparison with mild (0) and moderate (15%) acute respiratory distress syndrome(p = 0.02). No differences in PICU or hospital stay were observed across the groups. Conclusions: The Berlin definition can identify a subgroup of patients with distinctly worse outcomes, as shown by the increased mortality and reduced number of ventilator-free days in pediatric patients with severe acute respiratory distress syndrome.

Pulmonary surfactant in respiratory syncytial virus bronchiolitis: The role in pathogenesis and clinical implications

Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of lower respiratory tract infection, and the most frequent reason for hospitalization among infants throughout the world. In addition to the acute consequences of the disease, RSV bronchiolitis in early childhood is related to further development of recurrent wheezing and asthma. Despite the medical and economic burden of the disease, therapeutic options are limited to supportive measures, and mechanical ventilation in severe cases. Growing evidence suggests an important role of changes in pulmonary surfactant content and composition in the pathogenesis of severe RSV bronchiolitis. Besides the well‐known importance of pulmonary surfactant in maintenance of pulmonary homeostasis and lung mechanics, the surfactant proteins SP‐A and SP‐D are essential components of the pulmonary innate immune system. Deficiencies of such proteins, which develop in severe RSV bronchiolitis, may be related to impairment in viral clearance, and exacerbated inflammatory response. A comprehensive understanding of the role of the pulmonary surfactant in the pathogenesis of the disease may help the development of new treatment strategies. We conducted a review of the literature to analyze the evidences of pulmonary surfactant changes in the pathogenesis of severe RSV bronchiolitis, its relation to the inflammatory and immune response, and the possible role of pulmonary surfactant replacement in the treatment of the disease. Pediatr. Pulmonol. 2011; 46:415–420.

High Frequency of Staphylococcus Saprophyticus Urinary Tract Infections Among Female Adolescents.

Staphylococcus saprophyticus is a rarely reported agent of urinary tract infection (UTI) in the pediatric population. In our retrospective 3-year study, S. saprophyticus comprised 24.5% of 106 isolates of UTIs in female adolescents 12–15 years of age who attended an emergency department. Clinicians should be aware of the high prevalence of this etiology when empirically treating UTIs in female adolescents.

Distonia aguda relacionada ao uso de bromoprida em pacientes pediátricos

abstRact Objective: To report the case of two patients with acute dystonia induced by bromopride in children, followed by a review of the mechanisms of induction of movement dis-orders by antidopaminergic anti-emetic drugs, its clinical symptoms and treatment. Case description : Case 1: a 13 years old teenager who developed acute hypertonia and neck pain associated to fever and vomiting, suggestive of meningitis. Further investi-gation revealed that symptoms were associated with the ingestion of a single dose of bromopride. The symptoms stopped after administration of diphenidramine, preventing a spinal tap. Case 2: six months old infant who developed extrapyramidal movement disorder related to bromopride overdose, with prompt resolution of symptoms after treat-ment with biperiden. Comments: This seems to be the first report of acute dystonia after the use of bromopride in children. Although frequently used in Brazil as an anti-emetic and prokynetic agent, no clinical study has showed that bromopride has a better safety profile than other antidopaminergic anti-emetic drugs. While such studies are not available, caution is needed in the context of pediatric prescription of bromopride. Non pharmacological measures should be adopted in the manage-ment of vomiting and gastroesophageal reflux. If medical treatment cannot be avoided, one would rather use medica-tions with a better established safety profile.

Septic Shock, Necrotizing Pneumonitis, and Meningoencephalitis Caused by Mycoplasma pneumoniae in a Child: A Case Report

Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids

The Epidemiology of Sepsis in Childhood.

Background: Sepsis, or systemic inflammatory response to infection, is a major childhood disease and a common cause of death in children. Despite its importance, a global perspective on the epidemiology and mortality of pediatric sepsis across the world is still lacking. Methods: A non-systematic review of the medical articles published in Medline from 2005 to 2015. Results: Studies suggest that there has been a rise in the number of pediatric sepsis cases along the last two decades, which may relate to the increased survival of preterm and low birth-weight infants and children with severe chronic conditions. Children living in low-income countries represent a vulnerable population for sepsis. Despite several initiatives to improve the diagnosis and early treatment of pediatric sepsis, the mortality resulting from pediatric sepsis remains high, ranging from 5% to 40%. Poor outcomes, however, do not seem to be related to the limitation of resources but to the delay in the recognition and early treatment of sepsis. Conclusions: Educational efforts aiming to increase the awareness on sepsis by the general public and the adherence to the treatment guidelines by healthcare providers may result in significant improvements in sepsis survival. The global attention to pediatric sepsis, however, can only be achieved with the standardization of the definitions and the use of simple and sensitive diagnostic criteria that incorporate the differences in the necessities among different settings and the availability of local resources.

Epidemiology of Sepsis in Children Admitted to Picus in South America

Objectives: To report the prevalence of sepsis within the first 24 hours at admission and the PICU sepsis-related mortality among critically ill children admitted to PICU in South America. Design: A prospective multicenter cohort study. Setting: Twenty-one PICU, located in five South America countries. Patients: All children from 29 days to 17 years old admitted to the participating PICU between June 2011 and September 2011. Clinical, demographic, and laboratory data were registered within the first 24 hours at admission. Outcomes were registered upon PICU discharge or death. Interventions: None. Measurements and Main Results: Of the 1,090 patients included in this study, 464 had sepsis. The prevalence of sepsis, severe sepsis, and septic shock were 42.6%, 25.9%, and 19.8%, respectively. The median age of sepsis patients was 11.6 months (interquartile range, 3.2–48.7) and 43% had one or more prior chronic condition. The prevalence of sepsis was higher in infants (50.4%) and lower in adolescents (1.9%). Sepsis-related mortality was 14.2% and was consistently higher with increased disease severity: 4.4% for sepsis, 12.3% for severe sepsis, and 23.1% for septic shock. Twenty-five percent of deaths occurred within the first 24 hours at PICU admission. Multivariate analysis showed that higher Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores, the presence of two or more chronic conditions, and admission from pediatric wards were independently associated with death. Conclusions: We observed high prevalence of sepsis and sepsis-related mortality among this sample of children admitted to PICU in South America. Mortality was associated with greater severity of illness at admission and potentially associated with late PICU referral.

Fulminant Herpes Simplex Hepatitis Following a Short Course of Corticotherapy in a Child

Fulminant hepatitis (FH) is a rare condition defined by acute hepatocelular necrosis, coagulopathy, and encephalopathy, that develops within 8 weeks after the initial insult in a patient with no recognized previous liver disease. In children, encephalopathy may be of difficult recognition or late onset, and it is not essential for diagnosis of FH, but it may be useful for classification of severity of the disease. FH is a multisystem disorder. Besides impairment in liver function, hypotension, renal failure, higher susceptibility to infections, and multiple organ dysfunction may occur. Mortality ranges 29%, while the same number of patients requires liver transplantation. The etiology of FH differs around the world, according to social and economical features, prescription practices, and immunization status. In developed countries, acetaminophen overdose is the leading cause of acute liver failure, while in developing countries hepatitis A and B play a major role. Other causes of FH include idiosyncratic drug reactions, auto immune hepatitis, non-A non-B hepatitis, metabolic diseases, hypoperfusion secondary to shock, and undetermined causes. Herpes simplex virus (HSV) is a very unusual cause of FH. It comprises less than 1% cases of acute liver failure from viral etiology. It is a well known condition in pregnancy, newborns, and immunosupressed patients, and is very uncommon in immunocompetent ones. In all patient populations, the mortality rate is high. We report the first case of acute liver failure with a favorable outcome in an immunocompetent child who developed HSV FH following a short course corticosteroid therapy for treatment of status asthmaticus.

Comparison of main trials of recombinant human activated protein C in sepsis-are we encouraging more bleeding in neonates?

To the Editor: Since the section in Pediatric Critical Care Medicine focused on neonatal intensive care was first announced in January 2006, we were pleasantly surprised by continued publication of high-quality manuscripts in this area, including the observational study of Beshlawy et al (1) about the physiologic coagulation inhibitors: proteins C, S, and antithrombin III. Regarding this study, we would like to make a few considerations. First, there was an unintentional oversight of aforementioned Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study(2), the most relevant published study about recombinant human activated protein C (rh-aPC), in the references. Since its publication in 2001, PROWESS (2, 3) has been counted with 2504 citations (ISI-Web.of.Science in April 22, 2010), and is the cornerstone for rh-aPC therapy in adults. In that study, an absolute decrease in mortality of 6% and a number-needed-to-treat of 16 were demonstrated (2, 3). Second, we noted the absence of mortality scores for comparison with the high reported mortality (57%) in septic fullterm neonates (shown in Beshlawy’s Table 3) (1) and intracranial hemorrhage rate (23.3%) (1), which is 11 times higher than the baseline risk of bleeding reported in PROWESS (2%) (2). Finally, the conclusion by Beshlawy’s group (1) encourages “further placebocontrolled clinical trials to investigate the role of activated protein C and antithrombin-III in severe neonatal sepsis, and specially, in the states of DIC [disseminated intravascular coagulation].” Such a conclusion seems controversial to us, for the reasons specified below. When a specific pharmacologic treatment is recommended, it should target clear advantages that outweigh the possible side effects. This is far from true for almost the totality of physiologic coagulation inhibitors studies. In Table 1 , we have compiled seven of the most relevant trials on physiologic coagulation inhibitors (2–4) (n 13,244 patients), alongside the study of Beshlawy et al (1) (n 60 patients). Randomized controlled trials which evaluated the use of rh-aPC in adults with Acute Physiology and Chronic Health Evaluation 25 (Administration of Drotrecogin Alfa [Activated] in Early Stage Severe Sepsis [ADDRESS]) (3) and in children (Safety and Efficacy of Ranibizumab in Diabetic Macular Edema With Center Involvement [RESOLVE]) (3) failed to show any benefit in mortality but demonstrated an increase in bleeding risks (3, 5) (Table 1). Similarly, randomized controlled trials on antithrombin III (High-Dose Antithrombin III in Severe Sepsis Trial) (4) and recombinant tissue factor pathway inhibitor (Tifacogin/ Optimized Phase 3 Tifacogin in Multicenter Sepsis Trial [OPTIMIST]) (6) showed no improvement in 28-day mortality. Interestingly, the Extended Evaluation of Recombinant Human Activated Protein C (ENHANCE) trial was a single arm study, and impact on mortality was determined by historical comparisons with PROWESS’s placebo. In contrast, analyzing the risk of hazard shows an increase in the number of bleeding and severe bleeding events (3.5% to 10%) (2–4) secondary to physiologic coagulation inhibitors treatments. The only randomized controlled trial (PROWESS, 1690 patients) showing a treatment benefit over placebo has also demonstrated more severe bleeding (3.5% 2.0%, p .06) and intracranial hemorrhage (2). An editorial published in 2009 (5) noticed that the prevalence of serious bleeding during infusion is lower in studies sponsored by the manufacturers (mean, 2.5% to 3.4% in PROWESS/ADDRESS/ ENHANCE/MERCURY/Xigris and Prophylactic Heparin Evaluation in Severe Sepsis Study [XPRESS]/Wheeler) (5) than in independent studies (mean, 7.2% in Gentry/Bertolini/Kanji/ Voluntary Health Association and University Health System Consortium) (5). We calculated that the number needed to harm for serious bleeding in PROWESS was 66, and it ranges from 22 (ENHANCE), 40 (RESOLVE-Intracranial hemorrhage), 58 (ADDRESS), 52 (XPRESS) sponsored trials (Table 1) to 9.7 (Gentry), 11 (Bertolini), 12 (Kanji), 37 (Voluntary Health Association and University Health System Consortium) independent trials . Studies with adequate statistical power and negative results have strongly suggested the nonindication of those lowefficacy treatments in low-risk adults (3) and in pediatric patients(3). Therefore, recommendations for further studies with rh-aPC, antithrombin III, and tifacogin (r-TFPI) in neonates—a wellknown high-risk population for severe bleeding (23.3%) (1)—should be cautious and, possibly, reconsidered. We thank Dr. Débora Cristina Raulik Shieh of Universidade Federal do Paraná for her assistance in the preparation of the manuscript. The authors have not disclosed any potential conflicts of interest.