Operationalizing Appropriate Sepsis Definitions in Children Worldwide: Considerations for the Pediatric Sepsis Definition Taskforce.

Sepsis is a leading cause of global mortality in children, yet definitions for pediatric sepsis are outdated and lack global applicability and validity. In adults, the Sepsis-3 Definition Taskforce queried databases from high-income countries to develop and validate the criteria. The merit of this definition has been widely acknowledged; however, important considerations about less-resourced and more diverse settings pose challenges to its use globally. To improve applicability and relevance globally, the Pediatric Sepsis Definition Taskforce sought to develop a conceptual framework and rationale of the critical aspects and context-specific factors that must be considered for the optimal operationalization of future pediatric sepsis definitions. It is important to address challenges in developing a set of pediatric sepsis criteria which capture manifestations of illnesses with vastly different etiologies and underlying mechanisms. Ideal criteria need to be unambiguous, and capable of adapting to the different contexts in which children with suspected infections are present around the globe. Additionally, criteria need to facilitate early recognition and timely escalation of treatment to prevent progression and limit life-threatening organ dysfunction. To address these challenges, locally adaptable solutions are required, which permit individualized care based on available resources and the pretest probability of sepsis. This should facilitate affordable diagnostics which support risk stratification and prediction of likely treatment responses, and solutions for locally relevant outcome measures. For this purpose, global collaborative databases need to be established, using minimum variable datasets from routinely collected data. In summary, a "Think globally, act locally" approach is required.

Reporting of Social Determinants of Health in Pediatric Sepsis Studies.

OBJECTIVE: Standardized, consistent reporting of social determinants of health (SDOH) in studies on children with sepsis would allow for: 1) understanding the association of SDOH with illness severity and outcomes, 2) comparing populations and extrapolating study results, and 3) identification of potentially modifiable socioeconomic factors for policy makers. We, therefore, sought to determine how frequently data on SDOH were reported, which factors were collected and how these factors were defined in studies of sepsis in children. DATA SOURCES AND SELECTION: We reviewed 106 articles (published between 2005 and 2020) utilized in a recent systematic review on physiologic criteria for pediatric sepsis. DATA EXTRACTION: Data were extracted by two reviewers on variables that fell within the World Health Organization's SDOH categories. DATA SYNTHESIS: SDOH were not the primary outcome in any of the included studies. Seventeen percent of articles (18/106) did not report on any SDOH, and a further 36.8% (39/106) only reported on gender/sex. Of the remaining 46.2% of articles, the most reported SDOH categories were preadmission nutritional status (35.8%, 38/106) and race/ethnicity (18.9%, 20/106). However, no two studies used the same definition of the variables reported within each of these categories. Six studies reported on socioeconomic status (3.8%, 6/106), including two from upper-middle-income and four from lower middle-income countries. Only three studies reported on parental education levels (2.8%, 3/106). No study reported on parental job security or structural conflict. CONCLUSIONS: We found overall low reporting of SDOH and marked variability in categorizations and definitions of SDOH variables. Consistent and standardized reporting of SDOH in pediatric sepsis studies is needed to understand the role these factors play in the development and severity of sepsis, to compare and extrapolate study results between settings and to implement policies aimed at improving socioeconomic conditions related to sepsis.

Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce.

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock. DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020. STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract. DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed. DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001). CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

Challenges and health-care priorities for reducing the burden of paediatric sepsis in Latin America: a call to action.

Sepsis is a worldwide public health problem due to its high incidence and accompanying mortality, morbidity, and financial burden. It is a major cause of admission to paediatric intensive care units; despite advances in the diagnosis and treatment, both incidence and mortality are high in low-income and middle-income countries. There are several barriers in addressing the enormous burden of paediatric sepsis in these countries, which include: lack of data of incidence and mortality; unfamiliarity of sepsis by the lay public, leading to failure to seek care early, and by health professionals, leading to failure to treat emergently; and insufficient government funding for sepsis care programmes leading to inadequate staffing, material, and financial resources, and therefore, poor health systems. Socioeconomic inequalities, such as inequity and marked variation in income and education, high rates of malnutrition, high percentage of young population, and health systems that do not meet the population's demands also represent barriers in the care of children with sepsis in Latin America. In this Viewpoint, we draw attention to the problem of paediatric sepsis in Latin America and call for action to reduce the disease burden by proposing some solutions.

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.

OBJECTIVES: The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. DESIGN: Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. SETTING: PICU, Hospital Universitário da Universidade de São Paulo, Brazil. PATIENTS: Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. INTERVENTIONS: Patients were randomly assigned to receive either dopamine (5-10 µg/kg/min) or epinephrine (0.1-0.3 µg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. MEASUREMENTS AND MAIN RESULTS: Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. CONCLUSIONS: Dopamine was associated with an increased risk of death and healthcare-associated infection. Early administration of peripheral or intraosseous epinephrine was associated with increased survival in this population. Limitations should be observed while interpreting these results.

Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report.

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

[Availability of pediatric and neonatal intensive care units in the city of São Paulo]. / Disponibilidade de unidades de terapia intensiva pediátrica e neonatal no município de São Paulo.

OBJECTIVE: To describe the health care service provided in pediatric intensive care units in the city of São Paulo, by identifying and describing the units and analyzing their geographic distribution. METHODS: A descriptive cross-sectional study was carried out during a two-year period (August 2000 to July 2002). Data were collected through questionnaires answered by medical directors of each pediatric and neonatal intensive care unit. RESULTS: São Paulo is served by 107 pediatric and neonatal intensive care units, of which 85 (79.4%) completed and returned the questionnaire. We found a very unequal distribution of units as there were more units in places with the least pediatric population. Regarding to pediatric intensive care units specialization, 7% were pediatric, 41.2% were neonatal and 51.7% were mixed (pediatric and neonatal). Regarding hospital funds, 15.3% were associated with philanthropic institutions, 37.6% were private and 47% were public. A total of 1,067 beds were identified, of which 969 were active. The ratio bed/patient aged 0-14 was 1/2,728, varying from 1/604 at health districts-I to 1/6,812 at health districts-III. The units reported an average of 11.7 beds (2 to 60). The neonatal intensive care unit had a median of 16.9 beds per unit and pediatric intensive care units a median of 8.5 beds/unit. CONCLUSION: In São Paulo, we found an uneven distribution of pediatric and neonatal intensive care units among the health districts. There was also an uneven distribution between public and private units, and neonatal and pediatric ones. The current report is the first step in the effort to improve the quality of medical assistance in pediatric and neonatal intensive care units in São Paulo.

Disponibilidade de unidades de terapia intensiva pediátrica e neonatal no município de São Paulo / Availability of pediatric and neonatal intensive care units in the city of São Paulo

OBJETIVO: Caracterizar a assistência de saúde prestada em tratamento intensivo pediátrico e neonatal no município de São Paulo através da identificação, descrição e distribuição geográfica das unidades. MÉTODOS: Estudo descritivo, tipo transversal, onde foram estudadas as unidades de terapia intensiva pediátrica e neonatal do município de São Paulo, no período de agosto de 2000 a julho de 2002. A coleta dos dados foi realizada por meio de questionário preenchido pelo coordenador médico de cada unidade. RESULTADOS: Foram listadas 107 unidades de terapia intensiva pediátricas e neonatais no município de São Paulo. Oitenta e cinco (79,4 por cento) unidades forneceram os dados, constituindo a população de estudo. Observou-se maior número de unidades de terapia intensiva em Núcleos Regionais de Saúde com menor população pediátrica. Quanto à faixa etária, 7 por cento eram exclusivamente pediátricas, 41,2 por cento neonatais, e 51,7 por cento mistas. Em relação ao mantenedor: 47 por cento eram públicas, 37,6 por cento privadas, e 15,3 por cento filantrópicas. Identificamos 1.067 leitos, estando 969 em atividade. A razão leito/paciente de 0 a 14 anos foi de 1:2.728, variando de 1:604 (Núcleo Regional de Saúde - I) a 1:6.812 (Núcleo Regional de Saúde - III). O número de leitos por unidade variou de 2 a 60, com média de 11,7 (unidades de terapia intensiva neonatais: 16,9; mistas: 8,5). CONCLUSÃO: No município de São Paulo, observou-se uma distribuição desproporcional das unidades de terapia intensiva pediátrica e neonatal entre os cinco Núcleos Regionais de Saúde. Houve também uma distribuição desproporcional entre unidades de terapia intensiva públicas e privadas e entre neonatais e pediátricas. Esse estudo foi o primeiro esforço na busca por melhor qualidade na assistência intensiva pediátrica e neonatal no município de São Paulo.

[Comparison between an upper airway obstruction score and airway endoscopy to detect airway injury associated with endotracheal intubation in children]. / Comparação entre um escore de desconforto e a endoscopia respiratória para detecção de lesões de via aérea associadas à entubação traqueal em crianças.

OBJECTIVE: To compare an upper airway obstruction score vs. airway endoscopy to detect moderate or severe airway injury associated with endotracheal intubation in children. METHODS: Prospective study. Airway endoscopy and clinical evaluation were performed after extubation. Airway injuries identified on endoscopy or according to the upper airway obstruction score were classified as minor, moderate or severe. The obstruction score was assessed in terms of sensitivity, specificity, positive and negative predictive values and likelihood ratio to detect moderate or severe injuries. RESULTS: Among 215 patient, endoscopy was normal in 10.2%. Minor lesions were diagnosed in 54.9% of the patients, followed by moderate (24.2%) and severe (10.7%) lesions. In 163 patients with upper airway obstruction, the score classified injuries as minor in 23.3%, moderate in 41.4% and severe in 11.2%. A score > or = 4 had a sensitivity of 73.3% (95% CI: 67.4-79.2) to detect moderate or severe injuries and a specificity of 58.6% (95% CI: 52.0-65.2) to exclude patients without moderate or severe lesions. The positive predictive value of a score > or = 4 was 48.7% (95% CI: 42.0-55.4). In patients with a score < or = 3 the chance of not presenting moderate or severe injuries was 80.4% (95% CI: 75.1-85.7). The probability of a patient with moderate or severe injuries to present a score > or = 4 was 73.3% compared to patients without those injuries (41.4%) (1.8 fold higher). CONCLUSIONS: The score reliably ruled out moderate or severe airway injury in patients with minor upper airway distress. On the other hand, scores > or = 4 presented a low specificity. Clinical evaluation can be useful to rule out patients with minor airway injuries.

Comparaçäo entre um escore de desconforto e a endoscopia respiratória para detecçäo de lesöes de via aérea associadas à entubaçäo traqueal em crianças / Comparison between an upper airway obstruction score and airway endoscopy to detect airway injury associated with endotracheal intubation in children

OBJETIVOS: Analisar o desempenho de escore de desconforto alto na detecçäo de crianças com lesöes moderadas ou graves da via aérea associadas à intubaçäo traqueal, comparado à endoscopia respiratória. MÉTODOS: Estudo prospectivo. Endoscopia respiratória e avaliaçäo clínica realizadas após extubaçäo. As lesöes de via aérea e o escore de desconforto alto foram classificados em leves, moderados ou graves. O desempenho do escore foi analisado por meio de sua sensibilidade, especificidade, valores preditivos positivo, negativo e razäo de probabilidade em detectar pacientes com lesöes moderadas ou graves. RESULTADOS: Dentre 215 pacientes, 10,2 por cento apresentaram endoscopia normal. Lesöes leves foram diagnosticadas em 54,9 por cento dos pacientes, seguidas por moderadas (24,2 por cento) e graves (10,7 por cento). Em 163 pacientes com desconforto alto, o mesmo foi classificado como leve em 23,3 por cento, moderado em 41,4 por cento e grave em 11,2 por cento. Escore >4 apresentou sensibilidade de 73,3 por cento (IC 95 por cento: 67,4-79,2) em detectar lesäo moderada ou grave e especificidade de 58,6 por cento (IC 95 por cento:52,0-65,2) em excluir aqueles sem essas lesöes. Valor preditivo positivo do escore >4 foi 48,7 por cento (IC 95 por cento: 42,0-55,4), enquanto aqueles com escore < 3 apresentaram probabilidade de näo apresentar lesäo moderada ou grave de 80,4 por cento (IC 95 por cento: 75,1-85,7). A probabilidade de paciente com lesäo moderada ou grave apresentar escore >4 foi de 73,3 por cento em comparaçäo àqueles sem tais lesöes (41,4 por cento) (1,8 vez maior). CONCLUSÕES: O desempenho do escore foi satisfatório em sugerir ausência de lesäo moderada ou grave naqueles com desconforto leve. O mesmo näo foi observado para pacientes com escore >4. Avaliaçäo clínica pode ser útil como método de rastreamento e na exclusäo daqueles com lesäo leve