"Comparison between high-flow nasal cannula (HFNC) therapy and noninvasive ventilation (NIV) in children with acute respiratory failure by bronchiolitis: a randomized controlled trial".

BACKGROUND: The objective of this study was to compare HFNC therapy to noninvasive ventilation (NIV/BiPAP) in children with bronchiolitis who developed respiratory failure. We hypothesized that HFNC therapy would not be inferior to NIV. METHODS: This was a noninferiority open-label randomized single-center clinical trial conducted at a tertiary Brazilian hospital. Children under 2 years of age with no chronic conditions admitted for bronchiolitis that progressed to mild to moderate respiratory distress (Wood-Downes-Férres score < 8) were randomized to either the HFNC group or NIV (BiPAP) group through sealed envelopes. Vital signs, FiO2, Wood-Downes-Férres score and HFNC/NIV parameters were recorded up to 96 h after therapy initiation. Children who developed respiratory failure despite receiving initial therapy were intubated. Crossover was not allowed. The primary outcome analyzed was invasive mechanical ventilation requirement. The secondary outcomes were sedation usage, invasive mechanical ventilation duration, the PICU LOS, the hospital LOS, and mortality rate. RESULTS: A total of 126 patients were allocated to the NIV group (132 randomized and 6 excluded), and 126 were allocated to the HFNC group (136 randomized and 10 excluded). The median age was 2.5 (1-6) months in the NIV group and 3 (2-7) months in the HFNC group (p = 0,07). RSV was the most common virus isolated in both groups (72% vs. 71.4%, NIV and HFNC, respectively). Thirty-seven patients were intubated in the NIV group and 29 were intubated in the HFNC group (29% vs. 23%, p = 0.25). According to the Farrington-Manning test, with a noninferiority margin of 15%, the difference was 6.3% in favor of HFNC therapy (95% confidence interval: -4.5 to 17.1%, p < 0.0001). There was no significant difference in the PICU LOS or sedation duration. Sedation requirement, hospital LOS and invasive mechanical ventilation duration were lower in the HFNC group. CONCLUSION: HFNC therapy is noninferior to NIV in infants admitted with mild to moderate respiratory distress caused by bronchiolitis that progresses to respiratory failure. TRIAL REGISTRATION NUMBERS: U1111-1262-1740; RBR-104z966s. Registered 03/01/2023 (retrospectively registered). ReBEC: https://ensaiosclinicos.gov.br/rg/RBR-104z966s .

Undernutrition as an Aggravating Risk for Hospital Death in Critically Ill Children with Cancer.

OBJECTIVES: Undernourished children with cancer are at major risk for adverse outcomes. We intended to model nutritional status as risk factor for hospital death. METHODS: Retrospective analysis of two cohorts of children admitted in an oncology/hematology intensive care unit. Logistic regression was used for model building. RESULTS: The derivation cohort had 155 patients, with a median age of 104.9 mo., and 36 deaths (23.2%). Twenty-eight children (18.1%) had the z score of the body mass index < -2. A multivariate model with the variables "relapse of oncological disease" (Odds Ratio 3.14, P = 0.025), "surgical case" (OR 0.22, P = 0.002), "intubation/mechanical ventilation" (OR 8.38, P = 0.000) and "body mass index z score < -2" (OR 3.21, P = 0.024) generated a logit with good predictive capacity for "hospital death". In the validation cohort, with 450 patients (median age of 92.7 mo.), the model was able to predict 55.5 of the 58 observed deaths (Standardized Mortality Rate = 1.04, 95% CI 0.80-1.34, P = 0.72), with P = 0.68 in the Hosmer test. The AUC was 0.90 (95% CI 0.86-0.93). CONCLUSION: Undernutrition increases the risk of death, and is a variable that should be included in predictive mortality algorithms.

Prolonged Mechanical Ventilation in Children: Review of the Definition.

OBJECTIVES: To review existing definitions of prolonged mechanical ventilation in children. DESIGN: Review of the literature. SETTING: Not applicable. PATIENTS: Pediatric patients under mechanical ventilation. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: We searched the literature for original research on prolonged mechanical ventilation in children using the PubMed, Embase, and Cochrane Library databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and we extracted patient characteristics, duration of mechanical ventilation, outcomes, and associated complications. We identified 30 articles for qualitative analysis and found a wide variety of definitions, varying from 48 hours to 6 months. The most frequently used definitions of prolonged mechanical ventilation were greater than 7 days, greater than 14 days, and greater than 21 days. There was no high-quality evidence of a definition for prolonged mechanical ventilation in children. CONCLUSIONS: There is limited evidence to determine the definition of prolonged mechanical ventilation in children. The variety of definitions is a sign of the need for a consensus definition of pediatric prolonged mechanical ventilation.

The Impact of the Novel Coronavirus on Brazilian PICUs.

OBJECTIVES: To study the impact of the coronavirus disease 2019 pandemic, considering the physical distancing and schools closing, on the characteristics of admission and epidemiology on Brazilian PICUs. DESIGN: Observational, multicenter, time series analysis, of electronic medical records from 15 PICU in Brazil. Data consisted of all March, April, and May PICU admissions from 2017 to 2020. SETTING: Fifteen private PICUs in Brazil. PATIENTS: Pediatric patients admitted to the PICU from March to May since 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The period from March 11, 2020, to March 17, 2020, was considered the "intervention point" studied, corresponding to the suspension of school activities and the beginning of physical distancing in Brazil. During the pandemic period studied, there were 28 cases of coronavirus disease 2019 (one death). The mean age was higher (p = 0.000), the length of stay was shorter (p = 0.000), but mortality rates were similar among the periods (p = 0.36). The model estimated a reduction of 1,483 PICU admissions from March 2020 to May 2020. At the end of May, there was an estimated drop of -146.6 bronchiolitis admissions (95% CI, -242.8 to -50.3; p = 0.016); -71 asthma admissions (95% CI, -93.6 to -48.63; p = 0.000); and -59 community-acquired pneumonia admissions (95% CI, -74.7 to -43.3; p = 0.000) per period. The model showed no effect of the "intervention" (physical distancing) on hospitalization rates for epilepsy, diarrhea, sepsis, bacterial meningitis, or surgery when analyzed individually. When assessed together, the model estimated a reduction of 73.6 admissions (95% IC, -132 to -15.2; p = 0.43). CONCLUSIONS: The coronavirus disease 2019 pandemic strongly affected Brazilian PICUs, reducing admissions, length of stay, and the epidemiological profile. The measures to oppose the coronavirus disease 2019 pandemic may have prevented thousands of PICU hospitalizations across the country.

A pharmacokinetic model for voriconazole in a highly diversified population of children and adolescents with cancer.

BACKGROUND: The wide pharmacokinetic variability of voriconazole leads to uncertainty regarding adequate exposure. OBJECTIVES: To create a pharmacokinetic model that could help to explain the variability. METHODS: Retrospective review of paediatric patients with cancer. Models were built using Pmetrics. RESULTS: We analysed 158 trough measurements in 55 patients; in 41.8%, the serum levels were between 1 and 6 mg/L on initial measurement. After the measurements, dosage adjustments were made in 42 (76.3%) patients, and the percentage of adequate levels rose to 54.5%. Fourteen deaths (25.4%) were attributed to invasive fungal diseases. The mean serum levels were higher in deceased patients (mean ± SD: 3.1 ± 3.2 mg/L vs 2.5 ± 3.6 mg/L in survivors; P = 0.018), but the median doses per kg were higher in survivors. Drug exposure was also higher in deceased patients (mean ± SD of AUC: 19.2 ± 8.1 vs 9.5 ± 19.1 in survivors; P = 0.005). No correlation was found between serum concentrations <1 mg/L and death attributable to fungal disease. Bioavailability was estimated in 50%. The maximum velocity of clearance was reduced in deceased patients. CONCLUSIONS: Extremely ill patients can be poor metabolizers of voriconazole. Therapeutic monitoring promotes only a limited improvement in drug management.

Cytokine Kinetics in Febrile Neutropenic Children: Insights on the Usefulness as Sepsis Biomarkers, Influence of Filgrastim, and Behavior of the IL-23/IL-17 Pathway.

BACKGROUND: The study aimed to describe the kinetics of various cytokines from day 1 to day 14 of the onset of fever in neutropenic children and to evaluate their performances as discriminators of sepsis in the first 24 hours of fever, the possible influence of filgrastim, and the functioning of the IL-23/IL-17 axis. METHODS: IL-1ß, TNF-α, IL-10, IL-12/23p40, IL-21, IL-6, IL-8, IL-17, G-CSF, and GM-CSF were measured in plasma on days 1, 2, 3, 5, and 14 from the onset of fever in 35 patients. RESULTS: Thirteen patients (37.1%) developed sepsis. In mixed models, IL-6, IL-8, IL-10, and G-CSF showed higher estimated means in septic patients (P < 0.005), and IL-12/23p40 and IL-17 in nonseptic patients (P < 0.05). On day 1, IL-6, IL-8, and IL-10 appeared upregulated in patients who received filgrastim. Only IL-6, IL-8, IL-10, and procalcitonin were useful as discriminators of sepsis. Associating the markers with each other or to a risk assessment model improved performance. CONCLUSIONS: Cytokines kinetics showed proinflammatory and anti-inflammatory responses similar to what is described in nonneutropenic patients. IL-8, IL-6, IL-10, and procalcitonin are useful as early biomarkers of sepsis. Filgrastim upregulates expression of these markers, and we observed deficiency in the IL-23-IL-17 axis accompanying sepsis.

Assessment of newborn neuropsychomotor development born with exposure to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age.

OBJECTIVE: This study aimed to evaluate the Neuropsychomotor Development (NPMD) of newborns exposed to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age. METHODS: Childcare appointments were scheduled for the included newborns in the study. During the 6-month consultation, the Screening Test for Bayley III Scale and, based on it, children were classified as "low risk", "moderate risk" or "high risk" in the domains: of cognitive, receptive language, expressive language, fine motor, and gross motor. Those classified as "moderate risk"; or "high risk" received guidance about NPMD stimuli and were instructed to maintain follow-up. RESULTS: Only 13 (37.1 %) of the newborns were classified as low risk in receptive language and 18 (51.4 %) in gross motor skills, with the domains most affected. Prematurity was a risk for cognitive incompetence (moderate risk/high-risk classification) (coefficient: 1.89, Odds Ratio = 6.7, 95 % CI 1.3‒35, p = 0.02). Lower birth weight that 2.500g had a similar effect on cognitive incompetence (coefficient: 1.9, Odds Ratio = 6.2, 95 % CI 1.2‒32.2, p = 0.02). Exclusive breastfeeding at hospital discharge (n = 8) was protective for incompetence (high risk/moderate risk) in the language domain (coefficient -2.14, OR = 0.12, 95 % CI 0.02‒0.71, p = 0.02). CONCLUSIONS: The children included in the study must be monitored and their development monitored in order to clarify whether there is a relationship between the delay in NPMD and perinatal exposure to COVID-19, as delays were observed in these preliminary results.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects.

OBJECTIVE: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. METHOD: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. RESULTS: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007.  Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. CONCLUSIONS: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.

Patterns of Circulating Cytokines and Vascular Markers' Response in the Presence of COVID-19 in Kidney Transplant Recipients Compared with Non-Transplanted Patients.

COVID-19's severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients' differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs.

A case-control study of Clostridioides difficile symptomatic infections in a pediatric cancer hospital.

OBJECTIVE: The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer. METHODS: This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors. RESULTS: We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9). CONCLUSIONS: C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Knowledge regarding extracorporeal membrane oxygenation management among Brazilian pediatric intensivists: a cross-sectional survey.

OBJECTIVE: To assess Brazilian pediatric intensivists' general knowledge of extracorporeal membrane oxygenation, including evidence for its use, the national funding model, indications, and complications. METHODS: This was a multicenter cross-sectional survey including 45 Brazilian pediatric intensive care units. A convenience sample of 654 intensivists was surveyed regarding their knowledge on managing patients on extracorporeal membrane oxygenation, its indications, complications, funding, and literature evidence. RESULTS: The survey addressed questions regarding the knowledge and experience of pediatric intensivists with extracorporeal membrane oxygenation, including two clinical cases and 6 optional questions about the management of patients on extracorporeal membrane oxygenation. Of the 45 invited centers, 42 (91%) participated in the study, and 412 of 654 (63%) pediatric intensivists responded to the survey. Most pediatric intensive care units were from the Southeast region of Brazil (59.5%), and private/for-profit hospitals represented 28.6% of the participating centers. The average age of respondents was 41.4 (standard deviation 9.1) years, and the majority (77%) were women. Only 12.4% of respondents had taken an extracorporeal membrane oxygenation course. Only 19% of surveyed hospitals have an extracorporeal membrane oxygenation program, and only 27% of intensivists reported having already managed patients on extracorporeal membrane oxygenation. Specific extracorporeal membrane oxygenation management questions were responded to by only 64 physicians (15.5%), who had a fair/good correct response rate (median 63.4%; range 32.8% to 91.9%). CONCLUSION: Most Brazilian pediatric intensivists demonstrated limited knowledge regarding extracorporeal membrane oxygenation, including its indications and complications. Extracorporeal membrane oxygenation is not yet widely available in Brazil, with few intensivists prepared to manage patients on extracorporeal membrane oxygenation and even fewer intensivists recognizing when to refer patients to extracorporeal membrane oxygenation centers.

Tracheostomy practices in children on mechanical ventilation: a systematic review and meta-analysis.

OBJECTIVE: To evaluate current practices of tracheostomy in children regarding the ideal timing of tracheostomy placement, complications, indications, mortality, and success in decannulation. SOURCE OF DATA: The authors searched PubMed, Embase, Cochrane Library, Google Scholar, and complemented by manual search. The guidelines of PRISMA and MOOSE were applied. The quality of the included studies was evaluated with the Newcastle-Ottawa Scale. Information extracted included patients' characteristics, outcomes, time to tracheostomy, and associated complications. Odds ratios (ORs) with 95% CIs were computed using the Mantel-Haenszel method. SYNTHESIS OF DATA: Sixty-six articles were included in the qualitative analysis, and 8 were included in the meta-analysis about timing for tracheostomy placement. The risk ratio for "death in hospital outcome" did not show any benefit from performing a tracheostomy before or after 14 days of mechanical ventilation (p = 0.49). The early tracheostomy before 14 days had a great impact on the days of mechanical ventilation (-26 days in mean difference, p < 0.00001). The authors also found a great reduction in hospital length of stay (-31.4 days, p < 0.008). For the days in PICU, the mean reduction was of 14.7 days (p < 0.007). CONCLUSIONS: The meta-analysis suggests that tracheostomy performed in the first 14 days of ventilation can reduce the time spent on the ventilator, and the length of stay in the hospital, with no effect on mortality. The decision to perform a tracheostomy early or late may be more dependent on the baseline disease than on the time spent on ventilation .

Extracorporeal membrane oxygenation for respiratory failure in children: the years before and after the 2009 H1N1 pandemic. / Oxigenação por membrana extracorpórea na insuficiência respiratória em crianças: os anos antes e depois da pandemia de H1N1 de 2009.

OBJECTIVE: To evaluate whether there was any impact on the number of pediatric extracorporeal membrane oxygenation runs and survival rates in the years subsequent to the 2009 pandemic. METHODS: We studied two different periods of extracorporeal membrane oxygenation support for respiratory failure in children by analyzing datasets from the Extracorporeal Life Support Organization. Autoregressive integrated moving average models were constructed to estimate the effect of the pandemic. The year 2009 was the year of intervention (the H1N1 epidemic) in an interrupted time series model. Data collected from 2001 - 2010 were considered preintervention, and data collected from 2010 - 2017 were considered postintervention. RESULTS: There was an increase in survival rates in the period 2010 - 2017 compared to 2001 - 2010 (p < 0.0001), with a significant improvement in survival when extracorporeal membrane oxygenation was performed for acute respiratory failure due to viral pneumonia. The autoregressive integrated moving average model shows an increase of 23 extracorporeal membrane oxygenation runs per year, prior to the point of the level effect (2009). In terms of survival, the preslope shows that there was no significant increase in survival rates before 2009 (p = 0.41), but the level effect was nearly significant after two years (p = 0.05), with a 6% increase in survival. In four years, there was an 8% (p = 0.03) increase in survival, and six years after 2009, there was up to a 10% (p = 0.026) increase in survival. CONCLUSION: In the years following 2009, there was a significant, global incremental increase in the extracorporeal membrane oxygenation survival rates for all runs, mainly due to improvements in the technology and treatment protocols for acute respiratory failure related to viral pneumonia and other respiratory conditions.

OBJETIVO: Avaliar o impacto no número de casos de oxigenação por membrana extracorpórea e as taxas de sobrevivência nos anos seguintes à pandemia de H1N1 de 2009. MÉTODOS: Avaliaram-se dois períodos distintos de utilização de oxigenação por membrana extracorpórea como suporte para insuficiência respiratória em crianças, por meio da análise de conjuntos de dados da Extracorporeal Life Support Organization. Foram construídos modelos autorregressivos integrados de médias móveis para estimar os efeitos da pandemia. O ano de 2009 foi o ano de intervenção (epidemia de H1N1) em um modelo de séries temporais interrompidas. Os dados colhidos entre 2001 e 2010 foram considerados pré-intervenção e os obtidos entre 2010 e 2017 como pós-intervenção. RESULTADOS: Em comparação com o período entre 2001 e 2010, o período entre 2010 e 2017 mostrou aumento das taxas de sobrevivência (p < 0,0001), com melhora significante da sobrevivência quando se realizou oxigenação por membrana extracorpórea nos casos de insuficiência aguda por pneumonia viral. Antes do ponto de nível de efeito (2009), o modelo autorregressivo integrado de médias móveis mostrou aumento de 23 casos de oxigenação por membrana extracorpórea ao ano. Em termos de sobrevivência, a curva mostra que não houve aumento significante das taxas de sobrevivência antes de 2009 (p = 0,41), porém o nível de efeito foi próximo à significância após 2 anos (p = 0,05), com aumento de 6% na sobrevivência. Em 4 anos, ocorreu aumento de 8% (p = 0,03) na sobrevivência, e, 6 anos após 2009, a sobrevivência mostrou aumento de até 10% (p = 0,026). CONCLUSÃO: Nos anos após 2009, ocorreu significante e progressivo aumento global das taxas de sobrevivência com oxigenação por membrana extracorpórea para todos os casos, principalmente em razão de melhoras tecnológicas e dos protocolos de tratamento para insuficiência respiratória aguda relacionada à pneumonia viral e a outras condições respiratórias.

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.

Clinical practices related to high-flow nasal cannulas in pediatric critical care in Brazil compared to other countries: a Brazilian survey. / Práticas clínicas relacionadas a cânulas nasais de alto fluxo em terapia intensiva pediátrica no Brasil em comparação com as de outros países: um inquérito brasileiro.

OBJECTIVE: To describe current clinical practices related to the use of high-flow nasal cannula therapy by Brazilian pediatric intensivists and compare them with those in other countries. METHODS: A questionnaire was administered to pediatric intensivists in North and South America, Asia, Europe, and Australia/New Zealand for the main study. We compared the Brazilian cohort with cohorts in the United States of America, Canada, the United Kingdom, and India. RESULTS: Overall, 501 physicians responded, 127 of which were in Brazil. Only 63.8% of respondents in Brazil had a high-flow nasal cannula available, in contrast to 100% of respondents in the United Kingdom, Canada, and the United States. The attending physician was responsible for the decision to start a high-flow nasal cannula according to 61.2% respondents in Brazil, 95.5% in the United Kingdom, 96.6% in the United States, 96.8% in Canada, and 84.7% in India. A total of 62% of respondents in Brazil, 96.3% in the United Kingdom, 96.6% in the United States, 96.8% in Canada, and 84.7% in India reported that the attending physician was responsible for the decision to wean or modify the high-flow nasal cannula settings. When high-flow nasal cannula therapy failed due to respiratory distress/failure, 82% of respondents in Brazil would consider a trial of noninvasive ventilation before endotracheal intubation, compared to 93% in the United Kingdom, 88% in the United States, 91.5% in Canada, and 76.8% in India. More Brazilian intensivists (6.5%) than intensivists in the United Kingdom, United States, and India (1.6% for all) affirmed using sedatives frequently with high-flow nasal cannulas. CONCLUSION: The availability of high-flow nasal cannulas in Brazil is still not widespread. There are some divergences in clinical practices between Brazilian intensivists and their colleagues abroad, mainly in processes and decision-making about starting and weaning high-flow nasal cannula therapy.

OBJETIVO: Descrever as práticas clínicas atuais relacionadas à utilização de cânula nasal de alto fluxo por intensivistas pediátricos brasileiros e compará-las com as de outros países. MÉTODOS: Para o estudo principal, foi administrado um questionário a intensivistas pediátricos em países das Américas do Norte e do Sul, Ásia, Europa e Austrália/Nova Zelândia. Comparou-se a coorte brasileira com coortes dos Estados Unidos, Canadá, Reino Unido e Índia. RESULTADOS: Responderam ao questionário 501 médicos, dos quais 127 eram do Brasil. Apenas 63,8% dos participantes brasileiros tinham disponibilidade de cânula nasal de alto fluxo, em contraste com 100% dos participantes no Reino Unido, no Canadá e nos Estados Unidos. Coube ao médico responsável a decisão de iniciar a utilização de uma cânula nasal de alto fluxo segundo responderam 61,2% dos brasileiros, 95,5% dos localizados no Reino Unido, 96,6% dos participantes dos Estados Unidos, 96,8% dos médicos canadenses e 84,7% dos participantes da Índia; 62% dos participantes do Brasil, 96,3% do Reino Unido, 96,6% dos Estados Unidos, 96,8% do Canadá e 84,7% da Índia relataram que o médico responsável era quem definia o desmame ou modificava as regulagens da cânula nasal de alto fluxo. Quando ocorreu falha da cânula nasal de alto fluxo por desconforto respiratório ou insuficiência respiratória, 82% dos participantes do Brasil considerariam uma tentativa com ventilação não invasiva antes da intubação endotraqueal, em comparação com 93% do Reino Unido, 88% dos Estados Unidos, 91,5% do Canadá e 76,8% da Índia. Mais intensivistas brasileiros (6,5%) do que do Reino Unido, Estados Unidos e Índia (1,6% para todos) afirmaram utilizar sedativos com frequência concomitantemente à cânula nasal de alto fluxo. CONCLUSÃO: A disponibilidade de cânulas nasais de alto fluxo no Brasil ainda não é difundida. Há algumas divergências nas práticas clínicas entre intensivistas brasileiros e seus colegas estrangeiros, principalmente nos processos e nas tomadas de decisão relacionados a iniciar e desmamar o tratamento com cânula nasal de alto fluxo.

ALVEOLAR RECRUITMENT MANEUVERS FOR CHILDREN WITH CANCER AND ACUTE RESPIRATORY DISTRESS SYNDROME: A FEASIBILITY STUDY.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) can be a devastating condition in children with cancer and alveolar recruitment maneuvers (ARMs) can theoretically improve oxygenation and survival. The study aimed to assess the feasibility of ARMs in critically ill children with cancer and ARDS. METHODS: We retrospectively analyzed 31 maneuvers in a series of 12 patients (median age of 8.9 years) with solid tumors (n=4), lymphomas (n=2), acute lymphoblastic leukemia (n=2), and acute myeloid leukemia (n=4). Patients received positive end-expiratory pressure from 25 up to 40 cmH20, with a delta pressure of 15 cmH2O for 60 seconds. We assessed blood gases pre- and post-maneuvers, as well as ventilation parameters, vital signs, hemoglobin, clinical signs of pulmonary bleeding, and radiological signs of barotrauma. Pre- and post-values were compared by the Wilcoxon test. RESULTS: Median platelet count was 53,200/mm3. Post-maneuvers, mean arterial pressure decreased more than 20% in two patients, and four needed an increase in vasoactive drugs. Hemoglobin levels remained stable 24 hours after ARMs, and signs of pneumothorax, pneumomediastinum, or subcutaneous emphysema were absent. Fraction of inspired oxygen decreased significantly after ARMs (FiO2; p=0.003). Oxygen partial pressure (PaO2)/FiO2 ratio increased significantly (p=0.0002), and the oxygenation index was reduced (p=0.01), but all these improvements were transient. Recruited patients' 28-day mortality was 58%. CONCLUSIONS: ARMs, although feasible in the context of thrombocytopenia, lead only to transient improvements, and can cause significant hemodynamic instability.

The zero impact of the Vehicle Inspection Program on public health in São Paulo, SP.

OBJECTIVE To analyze the impact of two interventions (implementation and suspension of mandatory vehicle inspection) on morbidity and mortality due to conditions related to air pollution, from 2008 to 2017. METHODS Interrupted time series (ARIMA models), using data available in public repositories. RESULTS A total of 229,337 children of up to 5 years old were hospitalized due to respiratory diseases, and 1,053 died (average monthly mortality ratio for this population: 1.12/100,000). Exact 137,876 individuals over 40 years old were hospitalized for an acute myocardial infarction, and 19,492 died (3.7/100,000). A total of 11,010 individuals over 40 years old were hospitalized with malignant neoplasms of the respiratory system; 2,898 died (0.5/100,000). A total of 20,807 individuals over 60 years old were hospitalized with chronic obstructive pulmonary diseases; 2,627 died (1.5/100,000). As for strokes, 69,180 individuals were hospitalized, and 10,866 died (2.1/100,000). We found no significant regression coefficient for the implementation or suspension of the program regarding hospitalizations and deaths. 38,207 children of up to 14 years old were hospitalized with asthma, and 25 of them died (0.007/100,000). The coefficients show a monthly increase of 0.05 deaths/100,000 people (p = 0.01) in the post-inspection period. We found no correlation between the measured concentrations of the pollutants PM2.5 and CO - in a monitoring station, in the central region of the municipality - and the implementation or suspension of the inspection. CONCLUSIONS No evidence confirms that the program had a measurable beneficial impact on morbidity and mortality due to respiratory and circulatory diseases.

Practices related to assessment of sedation, analgesia and delirium among critical care pediatricians in Brazil.

OBJECTIVE: To understand the use of tools, protocols and comfort measures related to sedation/analgesia, and to screen the occurrence of delirium in pediatric intensive care units. METHODS: A survey with 14 questions was distributed by e-mail to Brazilian critical care pediatricians. Eight questions addressed physician and hospital demographics, and six inquired practices to assess sedation, analgesia, and delirium in pediatric intensive care units. RESULTS: Of 373 questionnaires sent, 61 were answered (16.3%). The majority of physicians were practicing in the Southeast region (57.2%). Of these, 46.5% worked at public hospitals, 28.6% of which under direct state administration. Of respondents, 57.1% used formal protocols for sedation and analgesia, and the Ramsay scale was the most frequently employed (52.5%). Delirium screening scores were not used by 48.2% of physicians. The Cornell Assessment of Pediatric Delirium was the score most often used (23.2%). The majority (85.7%) of physicians did not practice daily sedation interruption, and only 23.2% used non-pharmacological measures for patient comfort frequently, with varied participation of parents in the process. CONCLUSION: This study highlights the heterogeneity of practices for assessment of sedation/analgesia and lack of detection of delirium among critical care pediatricians in Brazil.

T helper type cytokines in sepsis: time-shared variance and correlation with organ dysfunction and hospital mortality.

OBJECTIVE: We evaluated the kinetics of cytokines belonging to the T helper1 (Th1), Th2, and Th17 profiles in septic patients, and their correlations with organ dysfunction and hospital mortality. METHODS: This was a prospective observational study in a cohort of septic patients admitted to the intensive care units (ICU) of three Brazilian general hospitals. A total of 104 septic patients and 53 health volunteers (controls) were included. Plasma samples were collected within the first 48h of organ dysfunction or septic shock (0D), after seven (D7) and 14 days (D14) of follow-up. The following cytokines were measured by flow cytometry: Interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10, IL-12/23p40, IL-17, IL-21, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF). RESULTS: IL-6, IL-8, G-CSF and IL-10 concentrations were higher in septic patients than in controls (p<0.001), while IL-12/23p40 presented higher levels in the controls (p=0.003). IL-6, IL-8 and IL-17 correlated with Sequential [Sepsis-related] Organ Failure Assessment (SOFA) D0, D1 and D3 (except for IL-6 at D0). IL-8 was associated with renal and cardiovascular dysfunction. In a mixed model analysis, IL-10 estimated means were lower in survivors than in deceased (p=0.014), while IL-21 had an estimated mean of 195.8pg/mL for survivors and 98.5 for deceased (p=0.03). Cytokines were grouped in four factors according to their kinetics over the three dosages (D0, D7, D14). Group 1 encompassed IL-6, IL-8, IL-10, IL-1ß, and G-CSF while Group 3 encompassed IL-17 and IL-12/23p40. Both correlated with SOFA (D0) (p=0.039 and p=0.003, respectively). IL-21 (Group 4) was higher in those who survived. IL-2, TNF-α and GM-CSF (Group 2) showed no correlation with outcomes. CONCLUSION: Inflammatory and anti-inflammatory cytokines shared co-variance in septic patients and were related to organ dysfunctions and hospital mortality.

The risks of the new morbidities acquired during pediatric onco-critical care and their life-shortening effects

Abstract Objective: The authors investigated the functional status at ICU admission and at hospital discharge, and the impact of dysfunctions on survivors' lifespan. Method: Single-center retrospective cohort. The FSS (Functional Status Scale) was calculated at ICU admission and at hospital discharge. A new morbidity was defined as an increase in FSS ≥ 3. Results: Among 1002 patients, there were 855 survivors. Of these, 194 (22.6%) had died by the end of the study; 45 (5.3%) had a new morbidity. Means in the motor domain at admission and discharge were 1.37 (SD: 0.82) and 1.53 (SD 0.95, p = 0.002). In the feeding domain, the means were 1.19 (SD 0.63) and 1.30 (SD 0.76), p = 0.002; global means were 6.93 (SD 2.45) and 7.2 (SD 2.94), p = 0.007. Acute respiratory failure requiring mechanical ventilation, the score PRISM IV, age < 5 years, and central nervous system tumors were independent predictors of new morbidity. New morbidity correlated with lower odds of survival after hospital discharge, considering all causes of death (p = 0.014), and was independently predictive of death (Cox hazard ratio = 1.98). In Weibull models, shortening in the life span of 14.2% (p = 0.014) was estimated as a new morbidity. Conclusions: New morbidities are related to age, disease severity at admission, and SNC tumors. New morbidities, in turn, correlate with lower probabilities of survival and shortening of the remaining life span. Physical rehabilitation interventions in this population of children may have the potential to provide an increase in lifespan.