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.

Measuring Social Health Following Pediatric Critical Illness: A Scoping Review and Conceptual Framework.

OBJECTIVE: Social health is an important component of recovery following critical illness as modeled in the pediatric Post-Intensive Care Syndrome framework. We conducted a scoping review of studies measuring social outcomes (measurable components of social health) following pediatric critical illness and propose a conceptual framework of the social outcomes measured in these studies. DATA SOURCES: PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Registry. STUDY SELECTION: We identified studies evaluating social outcomes in pediatric intensive care unit (PICU) survivors or their families from 1970-2017 as part of a broader scoping review of outcomes after pediatric critical illness. DATA EXTRACTION: We identified articles by dual review and dual-extracted study characteristics, instruments, and instrument validation and administration information. For instruments used in studies evaluating a social outcome, we collected instrument content and described it using qualitative methods adapted to a scoping review. DATA SYNTHESIS: Of 407 articles identified in the scoping review, 223 (55%) evaluated a social outcome. The majority were conducted in North America and the United Kingdom, with wide variation in methodology and population. Among these studies, 38 unique instruments were used to evaluate a social outcome. Specific social outcomes measured included individual (independence, attachment, empathy, social behaviors, social cognition, and social interest), environmental (community perceptions and environment), and network (activities and relationships) characteristics, together with school and family outcomes. While many instruments assessed more than one social outcome, no instrument evaluated all areas of social outcome. CONCLUSIONS: The full range of social outcomes reported following pediatric critical illness were not captured by any single instrument. The lack of a comprehensive instrument focused on social outcomes may contribute to under-appreciation of the importance of social outcomes and their under-representation in PICU outcomes research. A more comprehensive evaluation of social outcomes will improve understanding of overall recovery following pediatric critical illness.

Helicopter versus ground ambulance transport for interfacility transfer of critically ill children.

BACKGROUND: Following initial stabilization, critically ill children often require transfer to a specialized pediatric hospital. While the use of specialized pediatric transport teams has been associated with improved outcomes for these patients, the additional influence of transfer mode (helicopter or ground ambulance) on clinical outcomes remains unknown. METHODS: We investigated the association between transport mode and outcomes among critically ill children transferred to a single pediatric hospital via a specialized pediatric transport team. We designed a retrospective cohort study to reduce indication bias by limiting analysis to patients for whom a helicopter transport was initially requested. We compared outcomes for those who ultimately traveled via helicopter, and for those who ultimately traveled via ground ambulance due to non-clinical factors. RESULTS: We compared transport times, in-hospital mortality, and hospital length of stay by transport mode. Transport time in minutes was shorter for helicopter transports (median = 143, interquartile range [IQR]: 118-184) compared to ground ambulance transports (median = 289, IQR: 213-258; difference in medians = 146, 95% CI: 12 to 168, p < 0.001). In unadjusted analysis, helicopter transport was not associated with a difference in in-hospital mortality (helicopter = 6.0%, ground ambulance = 7.0%; 95% CI for difference: -6.6% to 3.3%; p = 0.64) but was associated with a statistically significant reduction in median hospital days (helicopter = 4, ground ambulance = 5; 95% CI -3 to 0; p = 0.04). In adjusted analyses, there were no statistically significant associations. These results were consistent across sensitivity analyses. CONCLUSIONS: Among critically ill pediatric patients without traumatic injuries transported by a specialty team, those patients who would have been transferred by helicopter if available but were instead transferred by ground ambulance reached their site of definitive care approximately 2.5 h later. Helicopter transport for these patients was not associated with in-hospital mortality, but was potentially associated with reduced hospital length of stay.

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.

Sepsis Subclasses: A Framework for Development and Interpretation.

Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.

Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for Pediatric Sepsis.

Importance: The death of a pediatric patient with sepsis motivated New York to mandate statewide sepsis treatment in 2013. The mandate included a 1-hour bundle of blood cultures, broad-spectrum antibiotics, and a 20-mL/kg intravenous fluid bolus. Whether completing the bundle elements within 1 hour improves outcomes is unclear. Objective: To determine the risk-adjusted association between completing the 1-hour pediatric sepsis bundle and individual bundle elements with in-hospital mortality. Design, Settings, and Participants: Statewide cohort study conducted from April 1, 2014, to December 31, 2016, in emergency departments, inpatient units, and intensive care units across New York State. A total of 1179 patients aged 18 years and younger with sepsis and septic shock reported to the New York State Department of Health who had a sepsis protocol initiated were included. Exposures: Completion of a 1-hour sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour. Main Outcomes and Measures: Risk-adjusted in-hospital mortality. Results: Of 1179 patients with sepsis reported at 54 hospitals (mean [SD] age, 7.2 [6.2] years; male, 54.2%; previously healthy, 44.5%; diagnosed as having shock, 68.8%), 139 (11.8%) died. The entire sepsis bundle was completed in 1 hour in 294 patients (24.9%). Antibiotics were administered to 798 patients (67.7%), blood cultures were obtained in 740 patients (62.8%), and the fluid bolus was completed in 548 patients (46.5%) within 1 hour. Completion of the entire bundle within 1 hour was associated with lower risk-adjusted odds of in-hospital mortality (odds ratio [OR], 0.59 [95% CI, 0.38 to 0.93], P = .02; predicted risk difference [RD], 4.0% [95% CI, 0.9% to 7.0%]). However, completion of each individual bundle element within 1 hour was not significantly associated with lower risk-adjusted mortality (blood culture: OR, 0.73 [95% CI, 0.51 to 1.06], P = .10; RD, 2.6% [95% CI, -0.5% to 5.7%]; antibiotics: OR, 0.78 [95% CI, 0.55 to 1.12], P = .18; RD, 2.1% [95% CI, -1.1% to 5.2%], and fluid bolus: OR, 0.88 [95% CI, 0.56 to 1.37], P = .56; RD, 1.1% [95% CI, -2.6% to 4.8%]). Conclusions and Relevance: In New York State following a mandate for sepsis care, completion of a sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour was associated with lower risk-adjusted in-hospital mortality among patients with pediatric sepsis and septic shock.

Sleep quality and its correlates in the first year of dialysis.

Although sleep problems are thought to be prevalent among patients who undergo dialysis, there is only limited information on the determinants of sleep quality and the change in sleep quality during the first year of dialysis treatment. This report uses data from a national cohort study of incident hemodialysis and peritoneal dialysis patients to identify the correlates of sleep quality and to determine the extent to which sleep quality is related to patients' health-related quality of life and survival. This report includes 909 incident dialysis patients who responded to questions about sleep quality. Three quarters of incident dialysis patients reported impaired sleep, and 14% had a decline in sleep quality in the first year of treatment. Poor sleep quality was significantly related to black race, higher serum phosphate, current smoking, benzodiazepine prescription, and complaints of severe restless legs. Poor baseline sleep quality was associated with lower SF-36 physical and mental component summary scores, vitality scores, and bodily pain scores (all P < 0.001). Younger age, current smoking, and benzodiazepine prescription were associated with decreases in sleep quality at 1 yr. There was no association between baseline sleep quality and survival; however, a decline in sleep quality during the first year on dialysis was associated with shorter survival (hazard ratio 1.44; 95% confidence interval 1.13 to 1.83; P = 0.003). Future work should examine the link between sleep quality and daytime functioning in the kidney failure population and the extent to which improving sleep quality will improve dialysis patient outcomes.

Skipped treatments, markers of nutritional nonadherence, and survival among incident hemodialysis patients.

BACKGROUND: Skipping hemodialysis treatments and failing to adhere to prescribed diets are thought to injure hemodialysis patients. METHODS: We examined predictors of hemodialysis skipping and laboratory measures of nonadherence and then examined the association of dialysis skipping and serum potassium and phosphate levels with survival. RESULTS: Of 739 patients, 67 were classified as skippers because they were absent for greater than 3% of scheduled treatments. Black race (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30 to 3.92), current smoking (OR, 1.79; 95% CI, 1.02 to 3.13), and use of illicit drugs (OR, 3.96; 95% CI, 2.16 to 7.24) were associated with skipping. White race, increased serum phosphate level, greater creatinine level, and lower body mass index increased the likelihood of a serum potassium level greater than 5.0 mEq/L (mmol/L); younger age, greater serum potassium level, and greater serum creatinine level were associated with a serum phosphate level greater than 5.5 mg/dL (>1.78 mmol/L). Skipping was associated with an increased risk for death (hazard ratio [HR], 1.69; 95% CI, 1.24 to 2.31), as were phosphate level greater than 5.5 mg/dL (HR, 1.59; 95% CI, 1.16 to 2.17) and potassium level greater than 5.0 mEq/L (HR, 1.50; 95% CI, 1.10 to 2.06). Skipping was associated with a lower likelihood of kidney transplantation in those younger than 65 years (OR, 0.41; 95% CI, 0.18 to 0.93). CONCLUSION: These findings show that hemodialysis patients of black race and those with current tobacco or illicit drug use are at risk for skipping dialysis treatments. Skipping treatments and markers of poor dietary adherence are strongly associated with greater risk for death. Targeting high-risk patients to understand reasons for nonadherence and to intervene could prevent premature death.

Comorbid conditions in kidney transplantation: association with graft and patient survival.

Although the impact of comorbidity on outcomes in ESRD has been evaluated extensively, its contribution after kidney transplantation has not been well studied. It is believed that comorbidity assessment is critical to the informed interpretation of kidney transplant outcomes. In this study, the Charlson Comorbidity Index was used to assess the comorbid conditions of 715 patients who underwent kidney transplantation at the Starzl Transplant Institute between January 1998 and January 2003. The impact of pretransplantation comorbidity on the development of acute cellular rejection after transplantation and on patient and graft survival was examined. The most common comorbid conditions among our patient population were diabetes (n = 217, 30.3%) and heart failure (n = 85, 11.9%). It was found the number of patients with high comorbidity at the Starzl Transplant Institute has increased significantly over time (P = 0.04). In multivariate adjusted models, high comorbidity was associated with an increased risk for patient death, both in the perioperative period (hazard ratio 3.20, 95% confidence interval 1.32 to 7.78; P = 0.01) and >3 mo after transplantation (hazard ratio 2.63; 95% confidence interval 1.62 to 4.28; P < 0.001). The Charlson Comorbidity Index is a practical tool for the evaluation of comorbidity in the transplant population, which has an increasing burden of comorbid disease. Increased comorbidity affects both perioperative and long-term patient outcomes and carries significant implications not only for the development of individual patient therapeutic strategies but also for the interpretation of patient trials and the development of policies that govern distribution of donor organs.

Post-transplantation growth among pediatric recipients of liver transplantation.

Improving a patient's quality-of-life (QOL) post-liver transplantation is of great importance. An aspect of improved QOL is the restoration of normal growth patterns in pediatric patients. To describe the post-transplantation growth patterns of 72 children included in the National Institute of Diabetes and Digestive and Kidney Diseases - Liver Transplantation Database (NIDDK-LTD), multilevel models were used, according to which children who waited more than a year for transplantation were smaller, compared with age and sex matched peers, at transplantation than children who waited less than a year while children who were growth retarded at transplantation experienced a larger yearly comparison height increase than children who were not growth retarded. The analysis also showed that boys older than 2 yr and younger than 13 yr at transplantation and girls older than 2 yr and younger than 11 yr at transplantation were significantly less growth retarded at transplantation than boys and girls under the age of 2 yr at transplantation.