A machine learning model for the early diagnosis of bloodstream infection in patients admitted to the pediatric intensive care unit.

Bloodstream infection (BSI) is associated with increased morbidity and mortality in the pediatric intensive care unit (PICU) and high healthcare costs. Early detection and appropriate treatment of BSI may improve patient's outcome. Data on machine-learning models to predict BSI in pediatric patients are limited and neither study included time series data. We aimed to develop a machine learning model to predict an early diagnosis of BSI in patients admitted to the PICU. This was a retrospective cohort study of patients who had at least one positive blood culture result during stay at a PICU of a tertiary-care university hospital, from January 1st to December 31st 2019. Patients with positive blood culture results with growth of contaminants and those with incomplete data were excluded. Models were developed using demographic, clinical and laboratory data collected from the electronic medical record. Laboratory data (complete blood cell counts with differential and C-reactive protein) and vital signs (heart rate, respiratory rate, blood pressure, temperature, oxygen saturation) were obtained 72 hours before and on the day of blood culture collection. A total of 8816 data from 76 patients were processed by the models. The machine committee was the best-performing model, showing accuracy of 99.33%, precision of 98.89%, sensitivity of 100% and specificity of 98.46%. Hence, we developed a model using demographic, clinical and laboratory data collected on a routine basis that was able to detect BSI with excellent accuracy and precision, and high sensitivity and specificity. The inclusion of vital signs and laboratory data variation over time allowed the model to identify temporal changes that could be suggestive of the diagnosis of BSI. Our model might help the medical team in clinical-decision making by creating an alert in the electronic medical record, which may allow early antimicrobial initiation and better outcomes.

Paediatric sepsis survivors are resistant to sepsis-induced long-term immune dysfunction.

BACKGROUND AND PURPOSE: Sepsis-surviving adult individuals commonly develop immunosuppression and increased susceptibility to secondary infections, an outcome mediated by the axis IL-33/ILC2s/M2 macrophages/Tregs. Nonetheless, the long-term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis. EXPERIMENTAL APPROACH: Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. Likewise, sepsis-surviving mice were inoculated intranasally with Pseudomonas aeruginosa or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis-surviving patients were collected and the concentration of IL-33 and Tregs frequency were assessed. KEY RESULTS: In contrast to 6-week-old mice, 2-week-old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in 6-week-old but not 2-week-old post-septic mice. Moreover, impaired IL-33 production in 2-week-old post-septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in 2-week-old mice. Clinically, adults but not paediatric post-septic patients exhibited higher counts of Tregs and seral IL-33 levels. CONCLUSION AND IMPLICATIONS: These findings demonstrate a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis.

Effect of manual hyperinflation with versus without positive end-expiratory pressure on dynamic compliance in pediatric patients following congenital heart surgery: A randomized controlled trial.

BACKGROUND: We aimed to compare the effect of manual hyperinflation with versus without positive end-expiratory pressure (PEEP) on dynamic compliance of the respiratory system in pediatric patients undergoing congenital heart surgery; to assess the safety of the technique in this population. METHODS: This was a randomized controlled trial conducted at the pediatric intensive care unit (PICU) of a tertiary-care hospital. Patients admitted to the PICU following cardiac surgery and receiving postoperative mechanical ventilation were randomized to the experimental or control group. Patients in the experimental group (n = 14) underwent manual hyperinflation with a PEEP valve set at 5 cm H2O, once daily, during the first 48 hours after surgery. Patients allocated to the control group (n = 16) underwent manual hyperinflation without PEEP, at the same time points. Lung mechanics was assessed before (T0) and 5 minutes (T5) after manual hyperinflation. The primary endpoint was dynamic compliance. Secondary outcomes included oxygen saturation index, duration of mechanical ventilation, length of stay, 28-day mortality and safety. RESULTS: Demographic and clinical characteristics were comparable in both groups. There was no significant difference in dynamic compliance between times in each group (Day 1: (mean) 0.78 vs 0.81 and 0.70 vs 0.77; Day 2: 0.85 vs 0.78 and 0.67 vs 0.68 mL/kg/cm H2O, in experimental and control groups, respectively; P > .05). Mean deltas of dynamic compliance were not significantly different between groups. The proportion of patients extubated <72 hours after surgery was similar in experimental and control groups (43% vs 50%, respectively; P = .73). Oxygen saturation index, length of stay, and 28-day mortality were not significantly different between groups. None of the patients had hemodynamic instability. CONCLUSIONS: Manual hyperinflation was safe and well tolerated in pediatric patients following surgery for congenital heart disease. No significant change in dynamic compliance of the respiratory system or in oxygenation was observed with the use of manual hyperinflation with or without PEEP in this population.

Cytomegalovirus Active Infection in Critically Ill Children.

OBJECTIVE: To describe the epidemiology, clinical characteristics and outcomes of children with cytomegalovirus (CMV) active infection in the pediatric intensive care unit (PICU) and to investigate risk factors for mortality. METHODS: This was a retrospective cohort study of patients who had CMV DNA detected in blood samples and/or tracheal aspirates by polymerase chain reaction (PCR) during stay at 2 PICUs of a university hospital. Suspected cases without etiological confirmation and patients with laboratory-confirmed CMV infection before PICU admission were excluded. RESULTS: Demographic, clinical and outcome data were collected from medical records. From January 1, 2012, to December 31, 2019, 4748 children were admitted to the PICUs. Thirty-five (0.74%; 95% CI 0.51%-1.02%) had laboratory-confirmed CMV active infection; 71.4% were immunocompromised and 11 (31.4%) died. Patients who died were older than those who survived (median age 65 vs. 5.5 months, respectively; P = 0.048), and they received antiviral therapy for a shorter time (median 12 vs. 23 days, respectively; P = 0.001). The main causa mortis was septic shock (82%) and in most deceased patients (73%) the last CMV PCR before death was positive. PELOD score >6 was a risk factor for death (RR 2.96; 95% CI 1.07-8.21). Viral load in blood had a poor ability for the prediction of death (area under the receiver operating characteristic curve 0.62; 95% CI 0.37-0.84). CONCLUSIONS: The incidence of CMV active infection during PICU stay was 0.74% in an upper-middle income country with a high CMV seroprevalence. PELOD score higher than 6 was a risk factor for death. No association was observed between CMV viral load and mortality.

Impact of children with complex chronic conditions on costs in a tertiary referral hospital.

OBJECTIVES: To investigate the impact of complex chronic conditions on the use of healthcare resources and hospitalization costs in a pediatric ward of a public tertiary referral university hospital in Brazil. METHODS: This is a longitudinal study with retrospective data collection. Overall, three one-year periods, separated by five-year intervals (2006, 2011, and 2016), were evaluated. Hospital costs were calculated in three systematic samples of 100 patients each, consisting of patients with and without complex chronic conditions in proportion to their participation in the studied year. RESULTS: Over the studied period, the hospital received 2,372 admissions from 2,172 patients. The proportion of hospitalized patients with complex chronic conditions increased from 13.3% in 2006 to 16.9% in 2016 as a result of a greater proportion of neurologically impaired children, which rose from 6.6% to 11.6% of the total number of patients in the same period. Patients' complexity also progressively increased, which greatly impacted the use of healthcare resources and costs, increasing by 11.6% from 2006 (R$1,300,879.20) to 2011 (R$1,452,359.71) and 9.4% from 2011 to 2016 (R$1,589,457.95). CONCLUSIONS: Hospitalizations of pediatric patients with complex chronic conditions increased from 2006 to 2016 in a Brazilian tertiary referral university hospital, associated with an important impact on hospital costs. Policies to reduce these costs in Brazil are greatly needed.

Prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic

Abstract Objective The proportion of children with complex chronic conditions is increasing in PICUs around the world. We determined the prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic. Methods The authors conducted a point prevalence cross-sectional study among fifteen Brazilian PICUs during the COVID-19 pandemic. The authors enrolled all children admitted to the participating PICUs with complex chronic conditions on three different days, four weeks apart, starting on April 4th, 2020. The authors recorded the patient's characteristics and functional status at admission and discharge days. Results During the 3 study days from March to June 2020, the authors enrolled 248 patients admitted to the 15 PICUs; 148 had CCC (prevalence of 59.7%). Patients had a median of 1 acute diagnosis and 2 chronic diagnoses. The use of resources/devices was extensive. The main mode of respiratory support was conventional mechanical ventilation. Most patients had a peripherally inserted central catheter (63.1%), followed by a central venous line (52.5%), and 33.3% had gastrostomy or/and tracheostomy. The functional status score was significantly better at discharge compared to admission day due to the respiratory status improvement. Conclusions The prevalence of children with CCC admitted to the Brazilian PICUs represented 59.7% of patients during the COVID-19 pandemic. The functional status of these children improved during hospitalization, mainly due to the respiratory component.

Risk factors for mortality from sepsis in an intensive care unit in Ecuador: A prospective study.

ABSTRACT: To investigate risk factors for mortality from sepsis in an intensive care unit (ICU) in Quito-Ecuador and their association to adherence to Surviving Sepsis Campaign recommendations.Prospective cohort study of patients with severe sepsis/septic shock admitted to the ICU of a public Ecuadorian hospital from March, 2018 to March, 2019. Demographic, clinical, treatment, and outcome data were collected from patients' health records. Patients were divided into 2 groups according to ICU survival or death. Log-binomial regression models were used to identify risk factors for mortality.In total, 154 patients were included. Patients who died in the ICU (n = 42; 27.3%) had higher sequential organ failure assessment score (median 11.5 vs 9; P<.01), more organ dysfunction (median 4 vs 3; P<.0001), and received greater volumes of fluid resuscitation in the first 6 hours (median 800 vs 600 mL; P = .01). Dysfunction of > 2 organs was a risk factor for mortality (relative risks [RR] 3.80, 95% CI 1.33-10.86), while successful early resuscitation (RR 0.32, 95% CI 0.15-0.70), successful empirical antibiotic treatment (RR 0.38, 95%CI 0.18-0.82), and antibiotic de-escalation (RR 0.28, 95%CI 0.13-0.61) were protective factors.Dysfunction of >2 organs was a risk factor for mortality from sepsis while successful early resuscitation and appropriate antibiotic treatment were protective.

Increased nutrition risk at admission is associated with longer hospitalization in children and adolescents with COVID-19.

BACKGROUND: We investigated the association of nutritional risk and inflammatory marker level with length of stay (LOS) in children and adolescents hospitalized for COVID-19 infection in two pediatric teaching hospitals in a developing country. METHODS: This was a cross-sectional analytical retrospective study performed in two pediatric hospitals. We included the data from all children and adolescents who were hospitalized with a SARS-CoV-2 infection between March and December 2020. Demographic, anthropometric, clinical, and laboratory data were extracted from electronic medical records. Nutritional risk was assessed according to the STRONGkids tool within 24 hours of admission and was categorized into two levels: ≥4 (high risk) and <4 (moderate or low risk). Means or medians were compared between nutritional risk groups using the t test and Mann-Whitney U test, respectively. The association of nutritional risk and inflammatory markers with LOS was estimated using the Kaplan-Meier method and log-rank test. Cox proportional-hazard and linear regression models were performed, and adjusted for sex, age, and respiratory symptoms. RESULTS: From a total of 73 patients, 20 (27.4%) had a STRONGkids score ≥4 at admission, which was associated with a longer LOS even after adjusting (ß = 12.30; 1.74-22.9 95% CI; P = 0.023). The same association was observed between LOS and all laboratory markers except for D-dimer. CONCLUSION: Among children and adolescents with COVID-19, a STRONGkids score ≥4 at admission, lower values of albumin, lymphocytes, and hemoglobin, and higher CRP values were associated with longer LOS.

Prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic.

OBJECTIVE: The proportion of children with complex chronic conditions is increasing in PICUs around the world. We determined the prevalence and functional status of children with complex chronic conditions in Brazilian PICUs during the COVID-19 pandemic. METHODS: The authors conducted a point prevalence cross-sectional study among fifteen Brazilian PICUs during the COVID-19 pandemic. The authors enrolled all children admitted to the participating PICUs with complex chronic conditions on three different days, four weeks apart, starting on April 4th, 2020. The authors recorded the patient's characteristics and functional status at admission and discharge days. RESULTS: During the 3 study days from March to June 2020, the authors enrolled 248 patients admitted to the 15 PICUs; 148 had CCC (prevalence of 59.7%). Patients had a median of 1 acute diagnosis and 2 chronic diagnoses. The use of resources/devices was extensive. The main mode of respiratory support was conventional mechanical ventilation. Most patients had a peripherally inserted central catheter (63.1%), followed by a central venous line (52.5%), and 33.3% had gastrostomy or/and tracheostomy. The functional status score was significantly better at discharge compared to admission day due to the respiratory status improvement. CONCLUSIONS: The prevalence of children with CCC admitted to the Brazilian PICUs represented 59.7% of patients during the COVID-19 pandemic. The functional status of these children improved during hospitalization, mainly due to the respiratory component.

Impact of children with complex chronic conditions on costs in a tertiary referral hospital

ABSTRACT OBJECTIVES To investigate the impact of complex chronic conditions on the use of healthcare resources and hospitalization costs in a pediatric ward of a public tertiary referral university hospital in Brazil. METHODS This is a longitudinal study with retrospective data collection. Overall, three one-year periods, separated by five-year intervals (2006, 2011, and 2016), were evaluated. Hospital costs were calculated in three systematic samples of 100 patients each, consisting of patients with and without complex chronic conditions in proportion to their participation in the studied year. RESULTS Over the studied period, the hospital received 2,372 admissions from 2,172 patients. The proportion of hospitalized patients with complex chronic conditions increased from 13.3% in 2006 to 16.9% in 2016 as a result of a greater proportion of neurologically impaired children, which rose from 6.6% to 11.6% of the total number of patients in the same period. Patients' complexity also progressively increased, which greatly impacted the use of healthcare resources and costs, increasing by 11.6% from 2006 (R$1,300,879.20) to 2011 (R$1,452,359.71) and 9.4% from 2011 to 2016 (R$1,589,457.95). CONCLUSIONS Hospitalizations of pediatric patients with complex chronic conditions increased from 2006 to 2016 in a Brazilian tertiary referral university hospital, associated with an important impact on hospital costs. Policies to reduce these costs in Brazil are greatly needed.

Epidemiology and factors associated with the severity of viral acute lower respiratory infection in children hospitalized in Manaus, Amazonas, in 2017-2018: An observational study.

ABSTRACT: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity.

Update on the diagnosis and management of COVID-19 in pediatric patients.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a pandemic in March 2020, affecting millions of people worldwide. However, COVID-19 in pediatric patients represents 1-5% of all cases, and the risk for developing severe disease and critical illness is much lower in children with COVID-19 than in adults. Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This review presents an update on the diagnostic methods for COVID-19, including reverse-transcriptase polymerase chain reaction (RT-PCR) tests, serology tests, and imaging, and summarizes the current recommendations for the management of the disease. Particular emphasis is placed on respiratory support, which includes noninvasive ventilation and invasive mechanical ventilation strategies according to lung compliance and pattern of lung injury. Pharmacological treatment, including pathogen-targeted drugs and host-directed therapies, has been addressed. The diagnostic criteria and management of MIS-C are also summarized.

COVID-19 Diagnostic and Management Protocol for Pediatric Patients.

This review aims to verify the main epidemiologic, clinical, laboratory-related, and therapeutic aspects of coronavirus disease 2019 (COVID-19) in critically ill pediatric patients. An extensive review of the medical literature on COVID-19 was performed, mainly focusing on the critical care of pediatric patients, considering expert opinions and recent reports related to this new disease. Experts from a large Brazilian public university analyzed all recently published material to produce a report aiming to standardize the care of critically ill children and adolescents. The report emphasizes on the clinical presentations of the disease and ventilatory support in pediatric patients with COVID-19. It establishes a flowchart to guide health practitioners on triaging critical cases. COVID-19 is essentially an unknown clinical condition for the majority of pediatric intensive care professionals. Guidelines developed by experts can help all practitioners standardize their attitudes and improve the treatment of COVID-19.

IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection.

BACKGROUND: Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. METHODS: Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. RESULTS: Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). CONCLUSIONS: An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.

Update on the diagnosis and management of COVID-19 in pediatric patients

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a pandemic in March 2020, affecting millions of people worldwide. However, COVID-19 in pediatric patients represents 1-5% of all cases, and the risk for developing severe disease and critical illness is much lower in children with COVID-19 than in adults. Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This review presents an update on the diagnostic methods for COVID-19, including reverse-transcriptase polymerase chain reaction (RT-PCR) tests, serology tests, and imaging, and summarizes the current recommendations for the management of the disease. Particular emphasis is placed on respiratory support, which includes noninvasive ventilation and invasive mechanical ventilation strategies according to lung compliance and pattern of lung injury. Pharmacological treatment, including pathogen-targeted drugs and host-directed therapies, has been addressed. The diagnostic criteria and management of MIS-C are also summarized.

Impacto prognóstico das complicações ocorridas durante o transporte de crianças gravemente doentes / Prognostic impact of complications during transport of critically ill children

Objetivo: o transporte de crianças gravemente doentes envolve particularidades que aumentam o risco de complicações. O objetivo foi investigar o impacto de complicações registradas durante o transporte na mortalidade geral e na taxa de alta hospitalar. Método: estudo realizado em duas etapas. A primeira foi um estudo transversal, no qual, através de entrevista padronizada, dirigida ao médico que admitiu essas crianças, foram identificadas potenciais complicações ocorridas durante o transporte. Três médicos independentes auditaram esses dados. A segunda etapa foi uma coorte prospectiva onde os pacientes divididos em dois grupos (com e sem complicações no transporte) foram seguidos prospectivamente. Resultados: 143 crianças foram incluídas no estudo. Pelo menos uma complicação durante o transporte foi observada em 74 delas (52%). A complicação mais prevalente foi relacionada a falhas no monitoramento e nos dispositivos (42%). A ocorrência de complicações no transporte foi associada a maior mortalidade hospitalar (Hazard ratio - HR): 5,60; intervalo de confiança de 95% (IC95%): 1,26 - 26,65; p=0,013) e a menor taxa de alta hospitalar (HR: 0,48; IC95%: 0,31 - 0,74; p = 0,0007). Após regressão de Cox para ajuste de fatores de confusão, a presença de complicações permaneceu associada à mortalidade hospitalar (HR: 6,74; IC95%: 1,40 - 32,34); p = 0,017), porém deixou de se associar com a taxa de alta hospitalar (HR: 0,76; IC95%: 0,49 - 1,16; p=0,213). Conclusão: presença de complicações durante o transporte pediátrico foi frequente na região metropolitana de Ribeirão Preto, São Paulo, Brasil. A ocorrência de complicações foi um preditor independente de mortalidade hospitalar.

Aims: Transport of critically ill children involves particularities that increase the risk of complications. The objective was to investigate the impact of these complications recorded during transport on overall mortality and hospital discharge rate. Method: Two-step study: the first was a cross-sectional study, in which, through standardized interviews with the doctor who admitted these children, potential complications during transport were identified. Three independent doctors audited this data. The second step was a prospective cohort, where patients divided into two groups (with and without transport complications) were followed prospectively. Results: One hundred and forty-three children were included in the study. At least one complication during transport was observed in 74 of them (52%). The most frequent complication was related to monitoring and device failures (42%). The occurrence of transport complications was associated with higher hospital mortality (Hazard ratio (HR): 5.60; 95% confidence interval (95%CI: 1.26 - 26.65; p = 0.013) and the lowest hospital discharge rate (HR: 0.48; 95%CI: 0.31 - 0.74; p = 0.0007). After Cox regression to adjust for confounding factors, the presence of complications remained associated with hospital mortality (HR: 6.74; 95%CI: 1.40 - 32.34; p = 0.017), but no remained associated with hospital discharge rate (HR: 0.76; 95%CI: 0.49 - 1.16; p = 0.213). Conclusion: The presence of complications during pediatric transport was frequent in metropolitan region of Ribeirão Preto, São Paulo, Brazil. The occurrence of complications was an independent predictor for hospital mortality.

COVID-19 diagnostic and management protocol for pediatric patients

This review aims to verify the main epidemiologic, clinical, laboratory-related, and therapeutic aspects of coronavirus disease 2019 (COVID-19) in critically ill pediatric patients. An extensive review of the medical literature on COVID-19 was performed, mainly focusing on the critical care of pediatric patients, considering expert opinions and recent reports related to this new disease. Experts from a large Brazilian public university analyzed all recently published material to produce a report aiming to standardize the care of critically ill children and adolescents. The report emphasizes on the clinical presentations of the disease and ventilatory support in pediatric patients with COVID-19. It establishes a flowchart to guide health practitioners on triaging critical cases. COVID-19 is essentially an unknown clinical condition for the majority of pediatric intensive care professionals. Guidelines developed by experts can help all practitioners standardize their attitudes and improve the treatment of COVID-19.

Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil.

OBJECTIVE: We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. DESIGN: Prospective observational cohort study. SETTING: A tertiary-care university hospital in Brazil. PATIENTS: Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal aspirates were collected from patients from June 1st, 2008 to May 31st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15-4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23-4.58) was independently associated with PICU admission. CONCLUSIONS: The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.

Spontaneous Breathing Trial for Prediction of Extubation Success in Pediatric Patients Following Congenital Heart Surgery: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the usefulness of a spontaneous breathing trial for predicting extubation success in pediatric patients in the postoperative period after cardiac surgery compared with a physician-led weaning. STUDY DESIGN: Randomized, controlled trial. SETTING: PICU of a tertiary-care university hospital. PATIENTS: A population of pediatric patients following cardiac surgery for congenital heart disease. INTERVENTIONS: Patients on mechanical ventilation for more than 12 hours after surgery who were considered ready for weaning were randomized to the spontaneous breathing trial group or the control group. The spontaneous breathing trial was performed on continuous positive airway pressure with the pressure support of 10 cmH2O, the positive end-expiratory pressure of 5 cmH2O, and the fraction of inspired oxygen less than or equal to 0.5 for 2 hours. Patients in the control group underwent ventilator weaning according to clinical judgment. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was extubation success defined as no need for reintubation within 48 hours after extubation. Secondary outcomes were PICU length of stay, hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality. One hundred and ten patients with the median age of 8 months were included in the study: 56 were assigned to the spontaneous breathing trial group and 54 were assigned to the control group. Demographic and clinical data and Risk Adjustment for Congenital Heart Surgery-1 classification were similar in both groups. Patients undergoing the spontaneous breathing trial had greater extubation success (83% vs 68%, p = 0.02) and shorter PICU length of stay (median 85 vs 367 hr, p < 0.0001) compared with the control group, respectively. There was no significant difference between groups in hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality. CONCLUSIONS: Pediatric patients with congenital heart disease undergoing the spontaneous breathing trial postoperatively had greater extubation success and shorter PICU length of stay compared with those weaned according to clinical judgment.

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis.

BACKGROUND: Neutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown. METHODS: Infant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured. RESULTS: Infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs. CONCLUSION: This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.