International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Predicting functional and quality-of-life outcomes following pediatric sepsis: performance of PRISM-III and PELOD-2.

BACKGROUND: Illness severity scores predict mortality following pediatric critical illness. Given declining PICU mortality, we assessed the ability of the Pediatric Risk of Mortality-III (PRISM) and Pediatric Logistic Organ Dysfunction-2 (PELOD) scores to predict morbidity outcomes. METHODS: Among 359 survivors <18 years in the Life After Pediatric Sepsis Evaluation multicenter prospective cohort study, we assessed functional morbidity at hospital discharge (Functional Status Scale increase ≥3 points from baseline) and health-related quality of life (HRQL; Pediatric Quality of Life Inventory or Functional Status II-R) deterioration >25% from baseline at 1, 3, 6, and 12 months post-admission. We determined discrimination of admission PRISM and admission, maximum, and cumulative 28-day PELOD with functional and HRQL morbidity at each timepoint. RESULTS: Cumulative PELOD provided the best discrimination of discharge functional morbidity (area under the receive operating characteristics curve [AUROC] 0.81, 95% CI 0.76-0.87) and 3-month HRQL deterioration (AUROC 0.71, 95% CI 0.61-0.81). Prediction was inferior for admission PRISM and PELOD and for 6- and 12-month HRQL assessments. CONCLUSIONS: Illness severity scores have a good prediction of early functional morbidity but a more limited ability to predict longer-term HRQL. Identification of factors beyond illness severity that contribute to HRQL outcomes may offer opportunities for intervention to improve outcomes. IMPACT: Illness severity scores are commonly used for mortality prediction and risk stratification in pediatric critical care research, quality improvement, and resource allocation algorithms. Prediction of morbidity rather than mortality may be beneficial given declining pediatric intensive care unit mortality. The PRISM and PELOD scores have moderate to good ability to predict new functional morbidity at hospital discharge following pediatric septic shock but limited ability to predict health-related quality of life outcomes in the year following PICU admission. Further research is needed to identify additional factors beyond illness severity that may impact post-discharge health-related quality of life.

Association of Sex and Age with Mortality and Health-Related Quality of Life in Children with Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

Introduction: Sepsis is more common in males than females, but whether outcomes differ by sex in various pediatric age groups is unclear. The Life After Pediatric Sepsis Evaluation (LAPSE) was a multicenter prospective cohort study that evaluated health-related quality of life (HRQL) in children after community-acquired septic shock. In this secondary analysis, we evaluated whether male children are at increased risk of mortality or long-term decline in HRQL than female children by age group. Methods: Children (1 month-18 years) with community-acquired septic shock were recruited from 12 pediatric intensive care units in the U.S. Data included sex, age group (<1 year, 1-<13 years, 13-18 years), acute illness severity (acute organ dysfunction and inflammation), and longitudinal assessments of HRQL and mortality. Persistent decline in HRQL was defined as a 10% decrease in HRQL comparing baseline to 3 months following admission. Male and female children were stratified by age group and compared to evaluate the difference in the composite outcome of death or persistent decline in HRQL using the Cochran-Mantel-Haenszel test. Results: Of 389 children, 54.2% (n = 211) were male. Overall, 10% (21/211) of males and 12% (22/178) of females died by 3 months (p = 0.454). Among children with follow-up data, 41% (57/138) of males and 44% (48/108) of females died or had persistent decline in HRQL at 3 months (p = 0.636), with no observed difference by sex when stratified by age group. There was no significant difference in acute illness severity between males and females overall or stratified by age group. Conclusions: In this secondary analysis of the LAPSE cohort, HRQL, and mortality were not different between male and female children when stratified by age group. There were no significant differences by sex across multiple measures of illness severity or treatment intensity.

Change in Functional Status During Hospital Admission and Long-Term Health-Related Quality of Life Among Pediatric Septic Shock Survivors.

OBJECTIVES: To investigate whether change in functional status from pre-hospitalization baseline to hospital discharge is associated with long-term health-related quality of life (HRQL) among children surviving septic shock. DESIGN: Secondary analysis of Life After Pediatric Sepsis Evaluation (LAPSE), a prospective cohort study of children with community-acquired septic shock, enrolled from January 2014 to June 2017. SETTING: Twelve U.S. academic PICUs. PATIENTS: Children, 1 month to 18 years, who survived to hospital discharge and had follow-up data for HRQL at 3 and/or 12 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional Status Scale (FSS) was assessed around enrollment to ascertain baseline status (pre-hospitalization) and at 28 days or hospital discharge. Two measures of HRQL were utilized: children with significant development delay were measured with the Functional Status II-R (FSII-R); typically, developing children were measured with the Pediatric Quality of Life Inventory (PedsQL). Each group was analyzed separately with multivariable regression modeling to determine the association between change in FSS from baseline to day 28 and HRQL at 3 and 12 months from PICU admission. Of the original 389 LAPSE participants, 224 (58%) are included. Among children with developmental delay ( n = 88), worsened FSS was associated with lower FSII-R at 3 months from PICU admission (-2.02; 95% CI, -3.34 to -0.0.71; p = 0.003), but not 12 months. Among developmentally typical children ( n = 136), worsened FSS was associated with lower PedsQL at both 3 and 12 months. Developmentally typical children with a neurologic insult during the PICU stay had the largest decrement in PedsQL at 12 months (-14.04 mo; 95% CI, -22.15 to -5.94 mo; p < 0.001). However, worsened FSS remained associated with poor HRQL-PedsQL at 3 and 12 months, after controlling for neurologic events (both p < 0.001). CONCLUSIONS: Change in FSS during hospitalization for septic shock is associated with long-term reductions in HRQL and could serve as a useful tool for identifying children at risk for this sequela.

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.

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.

Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative.

OBJECTIVES: Assess clinical outcomes following PICU Liberation ABCDEF Bundle utilization. DESIGN: Prospective, multicenter, cohort study. SETTING: Eight academic PICUs. PATIENTS: Children greater than 2 months with expected PICU stay greater than 2 days and need for mechanical ventilation (MV). INTERVENTIONS: ABCDEF Bundle implementation. MEASUREMENT AND MAIN RESULTS: Over an 11-month period (3-mo baseline, 8-mo implementation), Bundle utilization was measured for 622 patients totaling 5,017 PICU days. Risk of mortality was quantified for 532 patients (4,275 PICU days) for correlation between Bundle utilization and MV duration, PICU length of stay (LOS), delirium incidence, and mortality. Utilization was analyzed as subject-specific (entire PICU stay) and day-specific (single PICU day). Median overall subject-specific utilization increased from 50% during the 3-month baseline to 63.9% during the last four implementation months ( p < 0.001). Subject-specific utilization for elements A and C did not change; utilization improved for B (0-12.5%; p = 0.007), D (22.2-61.1%; p < 0.001), E (17.7-50%; p = 0.003), and F (50-79.2%; p = 0.001). We observed no association between Bundle utilization and MV duration, PICU LOS, or delirium incidence. In contrast, on adjusted analysis, every 10% increase in subject-specific utilization correlated with mortality odds ratio (OR) reduction of 34%, p < 0.001; every 10% increase in day-specific utilization correlated with a mortality OR reduction of 1.4% ( p = 0.006). CONCLUSIONS: ABCDEF Bundle is applicable to children. Although enhanced Bundle utilization correlated with decreased mortality, increased utilization did not correlate with duration of MV, PICU LOS, or delirium incidence. Additional research in the domains of comparative effectiveness, implementation science, and human factors engineering is required to understand this clinical inconsistency and optimize PICU Liberation concept integration into clinical practice.

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.

Association of Pathogen Type With Outcomes of Children Encountering Community-Acquired Pediatric Septic Shock.

OBJECTIVES: To determine the association of pathogen type with mortality, functional status, and health-related quality of life (HRQL) among children at hospital discharge/1 month following hospitalization for septic shock. DESIGN: Secondary database analysis of a prospective, descriptive cohort investigation. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years old, enrolled from 2013 to 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Association of clinical outcomes with pathogen type was assessed for all patients and separately for surviving patients enrolled in the primary Life After Pediatric Sepsis Evaluation (LAPSE) investigation. For this secondary analysis, we predicted that age would be associated with pathogen type and outcomes, and accordingly, it was incorporated as a confounding variable in primary analyses. Among 389 children enrolled with septic shock, at 1 month/hospital discharge, we observed no statistically significant differences in relation to pathogen types for the composite outcome mortality or substantial new functional morbidity: no causative organism identified (27% [28/103]), pure viral infections (26% [24/91]), pure bacterial/fungal infections (25% [31/125]), and bacterial/fungal+viral coinfections (33% [23/70]). Similarly, we observed no statistically significant differences in relation to pathogen types for the composite outcome, mortality, or persistent serious deterioration of HRQL: no causative organism identified (43% [44/103]), pure viral infections (33% [30/91]), pure bacterial/fungal infections (46% [57/125]), and bacterial/fungal+viral coinfections (43% [30/70]). However, we did identify statistically significant associations between pathogen type and the outcome ventilator-free days ( p = 0.0083) and PICU-free days (0.0238). CONCLUSIONS: This secondary analysis of the LAPSE database identified no statistically significant association of pathogen type with composite mortality and morbidity outcomes. However, pathogen type may be associated with PICU resources employed to treat sepsis organ dysfunction. Ultimately, pediatric septic shock was frequently associated with adverse patient-centered, clinically meaningful outcomes regardless of infectious disease pathogen type.

The Association of Early Corticosteroid Therapy With Clinical and Health-Related Quality of Life Outcomes in Children With Septic Shock.

OBJECTIVES: Corticosteroids are commonly used in the treatment of pediatric septic shock without clear evidence of the potential benefits or risks. This study examined the association of early corticosteroid therapy with patient-centered clinically meaningful outcomes. DESIGN: Subsequent cohort analysis of data derived from the prospective Life After Pediatric Sepsis Evaluation (LAPSE) investigation. Outcomes among patients receiving hydrocortisone or methylprednisolone on study day 0 or 1 were compared with those who did not use a propensity score-weighted analysis that controlled for age, sex, study site, and measures of first-day illness severity. SETTING: Twelve academic PICUs in the United States. PATIENTS: Children with community-acquired septic shock 1 month to 18 years old enrolled in LAPSE, 2013-2017. Exclusion criteria included a history of chronic corticosteroid administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among children enrolled in LAPSE, 352 of 392 met analysis inclusion criteria, and 155 of 352 (44%) received early corticosteroid therapy. After weighting corticosteroid therapy administration propensity across potentially confounding baseline characteristics, differences in outcomes associated with treatment were not statistically significant (adjusted effect or odds ratio [95% CI]): vasoactive-inotropic support duration (-0.37 d [-1.47 to 0.72]; p = 0.503), short-term survival without new morbidity (1.37 [0.83-2.28]; p = 0.218), new morbidity among month-1 survivors (0.70 [0.39-1.23]; p = 0.218), and persistent severe deterioration of health-related quality of life or mortality at month 1 (0.70 [0.40-1.23]; p = 0.212). CONCLUSIONS: This study examined the association of early corticosteroid therapy with mortality and morbidity among children encountering septic shock. After adjusting for variables with the potential to confound the relationship between early corticosteroid administration and clinically meaningful end points, there was no improvement in outcomes associated with this therapy. Results from this propensity analysis provide additional justification for equipoise regarding corticosteroid therapy for pediatric septic shock and ascertain the need for a well-designed clinical trial to examine benefit/risk for this intervention.

Health Resource Use in Survivors of Pediatric Septic Shock in the United States.

OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

Choosing Wisely For Critical Care: The Next Five.

OBJECTIVES: To formulate new "Choosing Wisely" for Critical Care recommendations that identify best practices to avoid waste and promote value while providing critical care. DATA SOURCES: Semistructured narrative literature review and quantitative survey assessments. STUDY SELECTION: English language publications that examined critical care practices in relation to reducing cost or waste. DATA EXTRACTION: Practices assessed to add no value to critical care were grouped by category. Taskforce assessment, modified Delphi consensus building, and quantitative survey analysis identified eight novel recommendations to avoid wasteful critical care practices. These were submitted to the Society of Critical Care Medicine membership for evaluation and ranking. DATA SYNTHESIS: Results from the quantitative Society of Critical Care Medicine membership survey identified the top scoring five of eight recommendations. These five highest ranked recommendations established Society of Critical Care Medicine's Next Five "Choosing" Wisely for Critical Care practices. CONCLUSIONS: Five new recommendations to reduce waste and enhance value in the practice of critical care address invasive devices, proactive liberation from mechanical ventilation, antibiotic stewardship, early mobilization, and providing goal-concordant care. These recommendations supplement the initial critical care recommendations from the "Choosing Wisely" campaign.

Health-related quality of life outcome measures for children surviving critical care: a scoping review.

PURPOSE: Health-related quality of life (HRQL) has been identified as one of the core outcomes most important to assess following pediatric critical care, yet there are no data on the use of HRQL in pediatric critical care research. We aimed to determine the HRQL instruments most commonly used to assess children surviving critical care and describe study methodology, patient populations, and instrument characteristics to identify areas of deficiency and guide investigators conducting HRQL research. METHODS: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Registry for studies evaluating pediatric critical care survivors published 1970-2017. We used dual review for article selection and data extraction. RESULTS: Of 60,349 citations, 66 articles met inclusion criteria. The majority of studies were observational (89.4%) and assessed HRQL at one post-discharge time-point (86.4%), and only 10.6% of studies included a baseline assessment. Time to the first follow-up assessment ranged from 1 month to 10 years post-hospitalization (median 3 years, IQR 0.5-6). For 26 prospective studies, the median follow-up time was 0.5 years [IQR 0.25-1]. Parent/guardian proxy-reporting was used in 83.3% of studies. Fifteen HRQL instruments were employed, with four used in >5% of articles: the Health Utility Index (n = 22 articles), the Pediatric Quality of Life Inventory (n = 17), the Child Health Questionnaire (n = 16), and the 36-Item Short Form Survey (n = 9). CONCLUSION: HRQL assessment in pediatric critical care research has been centered around four instruments, though existing literature is limited by minimal longitudinal follow-up and infrequent assessment of baseline HRQL.

Health-Related Quality of Life After Community-Acquired Septic Shock in Children With Preexisting Severe Developmental Disabilities.

OBJECTIVES: To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children. DESIGN: Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation. SETTING: Twelve academic PICU in the United States. PATIENTS: Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock. INTERVENTIONS: Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child's health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores. CONCLUSIONS: Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed.

Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation.

OBJECTIVES: The Life After Pediatric Sepsis Evaluation investigation recently reported that one-third of children who survive sepsis experience significant health-related quality-of-life impairment compared with baseline at 1 year after hospitalization. Pediatric Sepsis Biomarker Risk Model is a multibiomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the Pediatric Sepsis Biomarker Risk Model biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term health-related quality-of-life morbidity among children with community-acquired septic shock. DESIGN: Secondary analysis. SETTING: Twelve academic PICUs. PATIENTS: A subset of Life After Pediatric Sepsis Evaluation subjects (n = 173) with available blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three predefined outcomes from the Life After Pediatric Sepsis Evaluation investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or persistent, serious deterioration of health-related quality of life (> 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). Pediatric Sepsis Biomarker Risk Model had an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.59-0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, Pediatric Sepsis Biomarker Risk Model was not independently associated with increased odds of the composite outcome of mortality or deterioration of persistent, serious deterioration health-related quality of life greater than 25% below baseline. A new decision tree using the Pediatric Sepsis Biomarker Risk Model biomarkers had an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.80-0.95) for estimating the risk of persistent, serious deterioration health-related quality of life at 3 months among children who survived septic shock. CONCLUSIONS: Pediatric Sepsis Biomarker Risk Model had modest performance for estimating hospital mortality in an external cohort of children with community-acquired septic shock. The Pediatric Sepsis Biomarker Risk Model biomarkers appear to have utility for estimating the risk of persistent, serious deterioration of health-related quality of life up to 3 months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long-term health-related quality-of-life morbidity among children who survive septic shock.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children.

BACKGROUND: Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. METHODS: In a trial conducted at 37 children's hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. RESULTS: The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. CONCLUSIONS: Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach.

OBJECTIVES: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches. DESIGN: Retrospective, observational cohort study. SETTING: PICU and cardiac ICU, Seattle Children's Hospital, Seattle, WA. PATIENTS: A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis. CONCLUSIONS: The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.

Critical Illness Factors Associated With Long-Term Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: A companion article reports the trajectory of long-term mortality and significant health-related quality of life disability among children encountering septic shock. In this article, the investigators examine critical illness factors associated with these adverse outcomes. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve United States academic PICUs. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Illness severity, organ dysfunction, and resource utilization data were collected during PICU admission. Change from baseline health-related quality of life at the month 3 follow-up was assessed by parent proxy-report employing the Pediatric Quality of Life Inventory or the Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: In univariable modeling, critical illness variables associated with death and/or persistent, serious health-related quality of life deterioration were candidates for multivariable modeling using Bayesian information criterion. The most clinically relevant multivariable models were selected among models with near-optimal statistical fit. Three months following septic shock, 346 of 389 subjects (88.9%) were alive and 43 of 389 had died (11.1%); 203 of 389 (52.2%) had completed paired health-related quality of life surveys. Pediatric Risk of Mortality, cumulative Pediatric Logistic Organ Dysfunction scores, PICU and hospital durations of stay, maximum and cumulative vasoactive-inotropic scores, duration of mechanical ventilation, need for renal replacement therapy, extracorporeal life support or cardiopulmonary resuscitation, and appearance of pathologic neurologic signs were associated with adverse outcomes in univariable models. In multivariable regression analysis (odds ratio [95% CI]), summation of daily Pediatric Logistic Organ Dysfunction scores, 1.01/per point (1.01-1.02), p < 0.001; highest vasoactive-inotropic score, 1.02/per point (1.00-1.04), p = 0.003; and any acute pathologic neurologic sign/event, 5.04 (2.15-12.01), p < 0.001 were independently associated with death or persistent, serious deterioration of health-related quality of life at month 3. CONCLUSIONS AND RELEVANCE: Biologically plausible factors related to sepsis-associated critical illness organ dysfunction and its treatment were associated with poor outcomes at month 3 follow-up among children encountering septic shock.

Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life. CONCLUSIONS: This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.