SIRS o no SIRS: ¿es esa la infección? Una revisión crítica de los criterios de definición de sepsis / SIRS or not SIRS: Is that the infection? A critical review of the sepsis definition criteria

Resumen El enfoque moderno de la sepsis se ha centrado en la creación de consensos globales que utilizan distintos criterios para pesquisarla en forma precoz, con el fin de disminuir la morbimortalidad asociada a ella. Hasta la aparición del tercer y último consenso de adultos (Sepsis-3), el síndrome de respuesta inflamatoria sistémica (SIRS) fue el pilar diagnóstico utilizado por defecto en todas las edades. En Sepsis-3 se decidió retirar el SIRS, lo que generó un debate internacional sobre la oportunidad de dicho cambio. Esta revisión narrativa desarrolla la historia de las distintas definiciones de sepsis centradas en SIRS, las fortalezas, las debilidades y la pertinencia de los distintos elementos que ocasionaron el debate. Dada la ausencia de actualizaciones pediátricas en Sepsis-3, se hace especial énfasis en las implicaciones para las futuras definiciones de sepsis en esta etapa de la vida.

Abstract The modern approach to sepsis has focused on creating a global consensus with different criteria to early investigate it in order to reduce the morbidity and mortality associated with this complex entity. Until the third and last consensus of adults (Sepsis-3), the systemic inflammatory response syndrome (SIRS) was the diagnostic pillar used by default for all ages. In Sepsis-3, it was decided to withdraw the SIRS, which generated an international debate about the timing of such change. This narrative review develops the history of the different definitions of sepsis focused on SIRS, their strengths and weaknesses, and the relevance of the different elements that caused the debate. Given the absence of pediatric updates in Sepsis-3, a particular emphasis is placed on the implications for future definitions of sepsis at this stage of life

SIRS or not SIRS: Is that the infection? A critical review of the sepsis definition criteria.

The modern approach to sepsis has focused on creating a global consensus with different criteria to early investigate it in order to reduce the morbidity and mortality associated with this complex entity. Until the third and last consensus of adults (Sepsis-3), the systemic inflammatory response syndrome (SIRS) was the diagnostic pillar used by default for all ages. In Sepsis-3, it was decided to withdraw the SIRS, which generated an international debate about the timing of such change. This narrative review develops the history of the different definitions of sepsis focused on SIRS, their strengths and weaknesses, and the relevance of the different elements that caused the debate. Given the absence of pediatric updates in Sepsis-3, a particular emphasis is placed on the implications for future definitions of sepsis at this stage of life.

El enfoque moderno de la sepsis se ha centrado en la creación de consensos globales que utilizan distintos criterios para pesquisarla en forma precoz, con el fin de disminuir la morbimortalidad asociada a ella. Hasta la aparición del tercer y último consenso de adultos (Sepsis-3), el síndrome de respuesta inflamatoria sistémica (SIRS) fue el pilar diagnóstico utilizado por defecto en todas las edades. En Sepsis-3 se decidió retirar el SIRS, lo que generó un debate internacional sobre la oportunidad de dicho cambio. Esta revisión narrativa desarrolla la historia de las distintas definiciones de sepsis centradas en SIRS, las fortalezas, las debilidades y la pertinencia de los distintos elementos que ocasionaron el debate. Dada la ausencia de actualizaciones pediátricas en Sepsis-3, se hace especial énfasis en las implicaciones para las futuras definiciones de sepsis en esta etapa de la vida.

Prognostic relevance and inter-observer reliability of chest-imaging in pediatric ARDS: a pediatric acute respiratory distress incidence and epidemiology (PARDIE) study.

PURPOSE: Definitions of acute respiratory distress syndrome (ARDS) include radiographic criteria, but there are concerns about reliability and prognostic relevance. This study aimed to evaluate the independent relationship between chest imaging and mortality and examine the inter-rater variability of interpretations of chest radiographs (CXR) in pediatric ARDS (PARDS). METHODS: Prospective, international observational study in children meeting Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria for PARDS, which requires new infiltrate(s) consistent with pulmonary parenchymal disease, without mandating bilateral infiltrates. Mortality analysis focused on the entire cohort, whereas inter-observer variability used a subset of patients with blinded, simultaneous interpretation of CXRs by intensivists and radiologists. RESULTS: Bilateral infiltrates and four quadrants of alveolar consolidation were associated with mortality on a univariable basis, using CXRs from 708 patients with PARDS. For patients on either invasive (IMV) or non-invasive ventilation (NIV) with PaO2/FiO2 (PF) ratios (or SpO2/FiO2 (SF) ratio equivalent) > 100, neither bilateral infiltrates (OR 1.3 (95% CI 0.68, 2.5), p = 0.43), nor 4 quadrants of alveolar consolidation (OR 1.6 (0.85, 3), p = 0.14) were associated with mortality. For patients with PF ≤ 100, bilateral infiltrates (OR 3.6 (1.4, 9.4), p = 0.01) and four quadrants of consolidation (OR 2.0 (1.14, 3.5), p = 0.02) were associated with higher mortality. A subset of 702 CXRs from 233 patients had simultaneous interpretations. Interobserver agreement for bilateral infiltrates and quadrants was "slight" (kappa 0.31 and 0.33). Subgroup analysis showed agreement did not differ when stratified by PARDS severity but was slightly higher for children with chronic respiratory support (kappa 0.62), NIV at PARDS diagnosis (kappa 0.53), age > 10 years (kappa 0.43) and fluid balance > 40 ml/kg (kappa 0.48). CONCLUSION: Bilateral infiltrates and quadrants of alveolar consolidation are associated with mortality only for those with PF ratio ≤ 100, although there is high- inter-rater variability in these chest-x ray parameters.

Predicting Mortality in Children With Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome. DESIGN: Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia. SETTING: The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia. PATIENTS: There were 624 and 640 subjects in the derivation and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts. CONCLUSIONS: We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Rationale: Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).Objectives: To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Methods: This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.Measurements and Main Results: We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.Conclusions: The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.

Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

OBJECTIVES: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. DESIGN: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. SETTING: One hundred twenty-eight PICUs in 26 countries. PATIENTS: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. CONCLUSIONS: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.