ABSTRACT 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. Objective use model complications Methods crosssectional cross sectional 4 65 Results centers 91% 91 (91% study 41 63% 63 (63% 59.5%, 595 59.5% , 59 5 (59.5%) private/forprofit privateforprofit private/for profit private 286 28 28.6 414 41. standard 9.1 9 1 years 77% 77 (77% women 124 12 12.4 course 19 program 27 15.5%, 155 15.5% 15 (15.5%) fairgood fair good median 63.4% 634 328 32 8 32.8 91.9%. 919 91.9% . 91.9%) Conclusion (91 (63 59.5 (59.5% forprofit privatefor 2 28. 9. 7 (77 12. 15.5 (15.5% 63.4 3 32. 91.9 (9 (6 59. (59.5 (7 15. (15.5 63. 91. ( (59. (15. (59 (15 (5 (1

RESUMO Objetivo: Avaliar os conhecimentos gerais dos intensivistas pediátricos brasileiros sobre oxigenação por membrana extracorpórea, incluindo evidências de uso, modelo de custeio nacional, indicações e complicações. Métodos: Este estudo foi um inquérito transversal multicêntrico que incluiu 45 unidades de terapia intensiva pediátrica brasileiras. Realizou-se inquérito de conveniência com 654 intensivistas quanto aos seus conhecimentos sobre manejo de pacientes em oxigenação por membrana extracorpórea, suas indicações, complicações, custeio e evidências bibliográficas. Resultados: O inquérito abordou questões relativas aos conhecimentos e à experiência dos intensivistas pediátricos sobre oxigenação por membrana extracorpórea, incluindo dois casos clínicos e seis questões facultativas sobre o manejo de pacientes em oxigenação por membrana extracorpórea. Dos 45 centros convidados, 42 (91%) participaram do estudo, e 412 (63%) dos 654 intensivistas pediátricos responderam ao inquérito. A maioria das unidades de terapia intensiva pediátrica eram da Região Sudeste do Brasil (59,5%), e os hospitais privados com fins lucrativos representavam 28,6% dos centros participantes. A média de idade dos respondentes era de 41,4 (desvio-padrão de 9,1) anos, e a maioria (77%) era mulher. Apenas 12,4% dos respondentes tinham formação em oxigenação por membrana extracorpórea. Dos hospitais pesquisados, apenas 19% tinham um programa de oxigenação por membrana extracorpórea, e apenas 27% dos intensivistas declararam já ter manejado pacientes em oxigenação por membrana extracorpórea. Apenas 64 médicos (15,5%) responderam a questões específicas sobre o manejo de oxigenação por membrana extracorpórea (mediana 63,4%; oscilando entre 32,8% e 91,9%). Conclusão: A maioria dos intensivistas pediátricos brasileiros demonstrou conhecimentos limitados de oxigenação por membrana extracorpórea, incluindo suas indicações e complicações. A oxigenação por membrana extracorpórea ainda não está amplamente disponível no Brasil, com poucos intensivistas preparados para o manejo de pacientes em oxigenação por membrana extracorpórea e ainda menos intensivistas capazes de reconhecer quando devem encaminhar pacientes para centros de oxigenação por membrana extracorpórea. Objetivo uso nacional complicações Métodos 4 brasileiras Realizouse Realizou se 65 bibliográficas Resultados convidados 91% 91 (91% 41 63% 63 (63% 59,5%, 595 59,5% , 59 5 (59,5%) 286 28 6 28,6 participantes 414 41, desviopadrão desvio padrão 9,1 9 1 anos 77% 77 (77% mulher 124 12 12,4 pesquisados 19 27 15,5% 155 15 (15,5% mediana 63,4% 634 328 32 8 32,8 91,9%. 919 91,9% . 91,9%) Conclusão (91 (63 59,5 (59,5% 2 28, 9, 7 (77 12, 15,5 (15,5 63,4 3 32, 91,9 (9 (6 59, (59,5 (7 15, (15, 63, 91, ( (59, (15 (59 (1 (5

Abstract Introduction Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. Materials and methods Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. Results Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2= 0.5). Conclusions Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment. Grampositive Gram positive recipients regimen excluded 4060 40 60 40‒6 mgkgday mg kg day mg/kg/day steadystate steady state firstorder first order equations 24hour hour 24 CurveMinimum Curve Minimum AUC/MIC AUCMIC (AUC/MIC 600 included clearance halflife, halflife half life, life half-life respectively 21 2 2. 1.3‒2.8 1328 3 8 (1.3‒2.8 mLkgmin mL min mL/kg/min 33 3. 2.7‒4.4 2744 7 4 (2.7‒4.4 hours 07 0 0. 0.5‒0.9 0509 5 9 (0.5‒0.9 Lkg L L/kg 37 (3 % mgL mg/L adjustments R2= R2 R (R2 0.5. 05 0.5 . 0.5) AUCguided guided 406 40‒ 1.3‒2. 132 (1.3‒2. 2.7‒4. 274 (2.7‒4. 0.5‒0. 050 (0.5‒0. ( (R 1.3‒2 13 (1.3‒2 2.7‒4 27 (2.7‒4 0.5‒0 (0.5‒0 1.3‒ (1.3‒ 2.7‒ (2.7‒ 0.5‒ (0.5‒ 1.3 (1.3 2.7 (2.7 (0.5 1. (1. (2. (0. (1 (2 (0

RESUMO Objetivo: Avaliar a probabilidade de atingir o alvo pela razão entre a área sob a curva e a concentração inibitória mínima de vancomicina em pacientes pediátricos após o esquema de dose empírica e demonstrar a aplicabilidade desse método para o monitoramento da vancomicina. Metódos: Foi realizado um estudo de coorte retrospectivo que incluiu pacientes pediátricos com função renal normal internados entre janeiro e dezembro de 2020. O modelo de um compartimento com cinética de primeira ordem foi utilizado para estimar os parâmetros farmacocinéticos, e a área sob a curva foi calculada pela regra do trapézio. O alvo terapêutico foi definido como a razão entre a área sob a curva e a concentração inibitória mínima ≥ 400 e < 600. O teste do qui-quadrado foi aplicado para comparar a probabilidade de atingir o alvo nos grupos etários, enquanto os parâmetros farmacocinéticos foram comparados pelo teste de Kruskal-Wallis com o teste de Dunn para análises post hoc. Consideraram-se significativos os valores de p < 0,05. Resultados: Foram analisados, no total, 42 pares de níveis de vancomicina de 17 pacientes inscritos neste estudo. Após a dose diária empírica de vancomicina, o alvo terapêutico foi atingido em cinco (29%) pacientes; quatro pacientes (24%) apresentavam razão entre a área sob a curva inicial supraterapêutica e o valor de concentração inibitória mínima (> 600mg.h/L) e oito (47%) tinham valores subterapêuticos (< 400mg.h/L). Os patógenos mais identificados foram Staphylococcus spp. (n = 7). Os níveis de vale e as áreas sob a curva mostraram valores moderados de correlação (R2 = 0,73). Um (6%) paciente apresentou lesão renal aguda. Conclusão: A maioria dos pacientes não atingiu o alvo terapêutico com esquema de dose empírica de vancomicina, e a implementação de dosagem baseada na área sob a curva usando duas medições de amostra permitiu ajustes de dose em tempo real com base nos parâmetros farmacocinéticos dos indivíduos.

ABSTRACT Objective: To assess the percentage of vancomycin area under the curve/minimum inhibitory concentration target attainment in pediatric patients after the empirical dose regimen and to demonstrate the applicability of this method for vancomycin monitoring. Methods: A retrospective cohort study was performed including pediatric patients with normal renal function admitted between January 2020 and December 2020. The one-compartment model with first-order kinetics was used to estimate the pharmacokinetic parameters, and the area under the curve was calculated by the trapezoidal rule. The therapeutic target was defined as area under the curve/minimum inhibitory concentration ≥ 400 and < 600. The Chi-squared test was applied to compare the percentage of target attainment over age groups, while the pharmacokinetic parameters were compared by the Kruskal-Wallis test with Dunn’s test for post hoc analyses. We considered significant p-values < 0.05. Results: In total, 42 pairs of vancomycin levels were analyzed from 17 patients enrolled in this study. After empirical vancomycin daily dosing, the therapeutic target was achieved in five (29%) patients; four patients (24%) had a supratherapeutic initial area under the curve/minimum inhibitory concentration value (> 600mg.h/L), and eight (47%) patients had subtherapeutic values (< 400mg.h/L). The most identified pathogens were Staphylococcus spp. (n = 7). Trough levels and areas under the curve showed moderate correlation values (R2 = 0.73). Acute kidney injury occurred in one (6%) patient. Conclusion: Most patients did not reach the therapeutic target with a vancomycin empirical dose regimen, and the implementation of area under the curve-based dosing using two sample measurements allowed for real-time dose adjustments based on individuals’ pharmacokinetic parameters.

ABSTRACT Objective To describe the clinical characteristics and treatment of children with sepsis, severe sepsis, and septic shock at a pediatric emergency department of a public hospital. Methods A retrospective, observational study. The medical records of patients included in the hospital Pediatric Sepsis Protocol and patients with discharge ICD-10 A41.9 (sepsis, unspecified), R57 (shock) and A39 (meningococcal meningitis) were evaluated. Results A total of 399 patients were included. The prevalence of sepsis, severe sepsis, and septic shock at the emergency room were 0.41%, 0.14% and 0.014%, respectively. The median age was 21.5 months for sepsis, 12 months for severe sepsis, and 20.5 months for septic shock. Sepsis, severe sepsis, and septic shock were more often associated with respiratory diseases. The Respiratory Syncytial Virus was the most common agent. The median time to antibiotic and fluid administration was 3 hours in patients with sepsis and severe sepsis. In patients with septic shock, the median times to administer antibiotics, fluid and vasoactive drugs were 2 hours, 2.5 hours and 6 hours, respectively. The median length of hospital stay for patients with sepsis, severe sepsis and septic shock were 3 days, 4 days and 1 day, respectively. The overall mortality was 2%. Conclusion Sepsis had a low prevalence. Early diagnosis and recognition are a challenge for the emergency care pediatrician, the first place of admission.

Resumo Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID-19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico-epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilação mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilação mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID-19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Abstract Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.