Establishing the Knowledge and Skills Necessary in Pediatric Critical Care Medicine: A Systematic Approach to Practice Analysis.

OBJECTIVES: To describe the practice analysis undertaken by a task force convened by the American Board of Pediatrics Pediatric Critical Care Medicine Sub-board to create a comprehensive document to guide learning and assessment within Pediatric Critical Care Medicine. DESIGN: An in-depth practice analysis with a mixed-methods design involving a descriptive review of practice, a modified Delphi process, and a survey. SETTING: Not applicable. SUBJECTS: Seventy-five Pediatric Critical Care Medicine program directors and 2,535 American Board of Pediatrics Pediatric Critical Care Medicine diplomates. INTERVENTIONS: A practice analysis document, which identifies the full breadth of knowledge and skill required for the practice of Pediatric Critical Care Medicine, was developed by a task force made up of seven pediatric intensivists and a psychometrician. The document was circulated to all 75 Pediatric Critical Care Medicine fellowship program directors for review and comment and their feedback informed modifications to the draft document. Concurrently, data from creation of the practice analysis draft document were also used to update the Pediatric Critical Care Medicine, was developed by a task force made up of seven pediatric intensivists and a psychometrician. The document was circulated to all 75 Pediatrics Pediatric Critical Care Medicine fellowship program directors for review and comment and their feedback informed modifications to the draft document. Concurrently, data from creation of the practice analysis draft document were also used to update the Pediatric Critical Care Medicine content outline, which was sent to all 2,535 American Board of Pediatrics Pediatric Critical Care Medicine diplomates for review during an open-comment period between January 2019 and February 2019, and diplomate feedback was used to make updates to both the content outline and the practice analysis document. MEASUREMENTS AND MAIN RESULTS: After review and comment by 25 Pediatric Critical Care Medicine program directors (33.3%) and 619 board-certified diplomates (24.4%), a comprehensive practice analysis document was created through a two-stage process. The final practice analysis includes 10 performance domains which parallel previously published Entrustable Professional Activities in Pediatric Critical Care Medicine. These performance domains are made up of between three and eight specific tasks, with each task including the critical knowledge and skills that are necessary for successful completion. The final practice analysis document was also used by the American Board of Pediatrics Pediatric Critical Care Medicine Sub-board to update the Pediatric Critical Care Medicine content outline. CONCLUSIONS: A systematic approach to practice analysis, with stakeholder engagement, is essential for an accurate definition of Pediatric Critical Care Medicine practice in its totality. This collaborative process resulted in a dynamic document useful in guiding curriculum development for training programs, maintenance of certification, and lifetime professional development to enable safe and efficient patient care.

Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure: The Thrombocytopenia-Associated Multiple Organ Failure Network Prospective Experience.

OBJECTIVE: The objective was to compare the resolution of organ dysfunction, 28-day mortality, and biochemical markers in children with thrombocytopenia-associated multiple organ failure who received therapeutic plasma exchange versus no therapeutic plasma exchange. DESIGN: Observational longitudinal cohort study. SETTING: Nine U.S. PICUs. PATIENTS: Eighty-one children with sepsis-induced thrombocytopenia-associated multiple organ failure. INTERVENTIONS: Therapeutic plasma exchange. MEASUREMENTS AND MAIN RESULTS: Adjusted relative risk for 28-day mortality was modeled using standard multivariate regression with propensity score weighting to reduce covariate confounding. Change from baseline Pediatric Logistic Organ Dysfunction scores between therapeutic plasma exchange and no therapeutic plasma exchange differed in temporal pattern during the first week (p = 0.009). By day 4, mean Pediatric Logistic Organ Dysfunction score declined by 7.9 points (95% CI, -10.8 to -5.1) in the therapeutic plasma exchange-treated group compared with no change with no therapeutic plasma exchange. Use of therapeutic plasma exchange was associated with reduced 28-day mortality by multivariate analysis (adjusted relative risk, 0.45; 95% CI, 0.23-0.90; p = 0.02) and by propensity score weighting (adjusted relative risk, 0.46; 95% CI, 0.22-0.97; p = 0.04). CONCLUSIONS: Therapeutic plasma exchange use in thrombocytopenia-associated multiple organ failure was associated with a decrease in organ dysfunction. After accounting for several risk factors, 28-day all-cause mortality was lower in children treated with therapeutic plasma exchange compared with those receiving no therapeutic plasma exchange. A multicenter randomized clinical trial is necessary to determine a causal relationship.

State of the Unit: Physician Gender Diversity in Pediatric Critical Care Medicine Leadership.

Gender disparities in leadership are receiving increased attention throughout medicine and medical subspecialties. Little is known about the disparities in Pediatric Critical Care Medicine. In this piece, we explore gender disparities in Pediatric Critical Care Medicine physician leadership. We examine physician leadership in the Accreditation Council for Graduate Medical Education fellowship programs, as well as a limited sample of major Pediatric Critical Care Medicine textbooks and societies. Overall, the gender composition of division directors is not significantly different from that of workforce composition, although regional differences exist. More women than men lead fellowship programs, at a higher ratio compared with workforce composition. However, greater gender disparities are present in editorial leadership in this limited analysis. We conclude by recommending potential paths forward for further study and intervention, such as tracking gender diversity and being cognizant of the unique challenges that women currently experience in professional advancement.

Procalcitonin Levels in Critically Ill Children With Status Asthmaticus.

BACKGROUND: Children with status asthmaticus (SA) often present with fever and are evaluated with chest radiographs (CXRs). In the absence of a confirmatory test for bacterial infection, antibiotics are started whenever there are radiological infiltrates or if there is a suspicion of pneumonia. We undertook this study to determine if serum procalcitonin (PCT) levels at admission are altered in critically ill children with SA. We also sought to determine if serum PCT levels are elevated in children with radiological infiltrates or in children who were treated with antibiotics. METHODS: This is a prospective single-center observational study evaluating serum PCT levels in critically ill children with SA. Study subjects included children 1 to 21 years old, admitted to a pediatric intensive care unit (PICU) with SA between March 2012 and April 2013. For the purposes of this study, patients whose CXRs were read by the radiologist as probable bacterial pneumonia was defined as having "radiological bacterial pneumonia," whereas patients who received antibiotics by the treating physician were defined as having "clinician-diagnosed pneumonia." RESULTS: Sixty-one patients with a median age of 7.3 years (interquartile range, 4-10 years) were included in the study. Fifty-one percent were male. Average Pediatric Risk of Mortality III score was 2.7 (SD, 2.9). Three patients (5%) were determined to have radiological bacterial pneumonia, whereas 52 (85%) did not. Six patients (10%) were indeterminate. The mean PCT level for all patients was 0.65 (SD, 1.54) ng/mL, whereas the median PCT level was 0.3 ng/mL. There was no significant difference in the mean PCT levels between the patients with and without clinician-diagnosed pneumonia (0.33 [SD, 0.36] vs 0.69 [SD, 1.67], P = 0.44). Using a PCT cutoff level of 0.5 ng/mL, a significant association was found with the presence of fever (P = 0.004), but no significant association was found with the presence of CXR infiltrates, radiological bacterial pneumonia, hospital length of stay, PICU length of stay, Pediatric Risk of Mortality III scores, or receipt of antibiotics. CONCLUSIONS: Serum PCT level was not elevated to greater than 0.5 ng/mL in 75% of this cohort of critically ill children with SA admitted to PICU. Presence of CXR infiltrates was not associated with higher PCT levels. Large clinical trials are needed to study the diagnostic and predictive role of PCT in this patient population.

Therapeutic hypothermia after out-of-hospital cardiac arrest in children.

BACKGROUND: Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS: We conducted this trial of two targeted temperature interventions at 38 children's hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days 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 Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS: A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

Management of acute asthma exacerbations.

PURPOSE OF REVIEW: Herein, we review the current guidelines for the management of children with an acute asthma exacerbation. We focus on management in the emergency department, inpatient, and ICU settings. RECENT FINDINGS: The most recent statistics show that the prevalence of asthma during childhood has decreased in certain demographic subgroups and plateaued in other subgroups. However, acute asthma accounts for significant healthcare expenditures. Although there are few, if any, newer therapeutic agents available for management of acute asthma exacerbations, several reports leveraging quality improvement science have shown significant reductions in costs of care as well as improvements in outcome. SUMMARY: Asthma is one of the most common chronic conditions in children and the most common reason that children are admitted to the hospital. Nevertheless, the evidence to support specific agents in the management of acute asthma exacerbations is surprisingly limited. The management of acute exacerbations focuses on reversal of bronchospasm, correction of hypoxia, and prevention of relapse and recurrence. Second-tier and third-tier agents are infrequently used outside of the ICU setting. Reducing the variation in treatment is likely to lead to lower costs and better outcomes.

Sepsis in Pediatric Cardiac Intensive Care.

OBJECTIVES: In this review, we will discuss risk factors for developing sepsis; the role of biomarkers in establishing an early diagnosis, in monitoring therapeutic efficacy, in stratification, and for the identification of sepsis endotypes; and the pathophysiology and management of severe sepsis and septic shock, with an emphasis on the impact of sepsis on cardiovascular function. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: There is a lot of excitement in the field of sepsis research today. Scientific advances in the diagnosis and clinical staging of sepsis, as well as a personalized approach to the treatment of sepsis, offer tremendous promise for the future. However, at the same time, it is also evident that sepsis mortality has not improved enough, even with progress in our understanding of the molecular pathophysiology of sepsis.

Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

RATIONALE: Limited data exist about the international burden of severe sepsis in critically ill children. OBJECTIVES: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. METHODS: A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. MEASUREMENTS AND MAIN RESULTS: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. CONCLUSIONS: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

Critical Care Delivery: The Importance of Process of Care and ICU Structure to Improved Outcomes: An Update From the American College of Critical Care Medicine Task Force on Models of Critical Care.

In 2001, the Society of Critical Care Medicine published practice model guidelines that focused on the delivery of critical care and the roles of different ICU team members. An exhaustive review of the additional literature published since the last guideline has demonstrated that both the structure and process of care in the ICU are important for achieving optimal patient outcomes. Since the publication of the original guideline, several authorities have recognized that improvements in the processes of care, ICU structure, and the use of quality improvement science methodologies can beneficially impact patient outcomes and reduce costs. Herein, we summarize findings of the American College of Critical Care Medicine Task Force on Models of Critical Care: 1) An intensivist-led, high-performing, multidisciplinary team dedicated to the ICU is an integral part of effective care delivery; 2) Process improvement is the backbone of achieving high-quality ICU outcomes; 3) Standardized protocols including care bundles and order sets to facilitate measurable processes and outcomes should be used and further developed in the ICU setting; and 4) Institutional support for comprehensive quality improvement programs as well as tele-ICU programs should be provided.

Improving acute kidney injury diagnostics using predictive analytics.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a multifactorial syndrome affecting an alarming proportion of hospitalized patients. Although early recognition may expedite management, the ability to identify patients at-risk and those suffering real-time injury is inconsistent. The review will summarize the recent reports describing advancements in the area of AKI epidemiology, specifically focusing on risk scoring and predictive analytics. RECENT FINDINGS: In the critical care population, the primary underlying factors limiting prediction models include an inability to properly account for patient heterogeneity and underperforming metrics used to assess kidney function. Severity of illness scores demonstrate limited AKI predictive performance. Recent evidence suggests traditional methods for detecting AKI may be leveraged and ultimately replaced by newer, more sophisticated analytical tools capable of prediction and identification: risk stratification, novel AKI biomarkers, and clinical information systems. Additionally, the utility of novel biomarkers may be optimized through targeting using patient context, and may provide more granular information about the injury phenotype. Finally, manipulation of the electronic health record allows for real-time recognition of injury. SUMMARY: Integrating a high-functioning clinical information system with risk stratification methodology and novel biomarker yields a predictive analytic model for AKI diagnostics.

Is the "golden age" of the "golden hour" in sepsis over?

The so-called "golden hour" of trauma resuscitation has been applied to a number of disease conditions in the intensive care unit (ICU) setting. For example, the "golden hour" as applied to the treatment of critically children and adults with severe sepsis and septic shock is based upon early recognition, early administration of antibiotics, and early reversal of the shock state. However, several clinical studies published over the last decade have called into question this time-honored approach and suggest that overly aggressive fluid resuscitation may cause more harm than good. Perhaps we are finally leaving the "Golden Age" of the "golden hour" and entering a new age in which we are able to use a more personalized approach to fluid management for patients with severe sepsis/septic shock.

A Case-Control Study on the Impact of Ventilator-Associated Tracheobronchitis in the PICU.

OBJECTIVES: Hospital-acquired infections increase morbidity, mortality, and charges in the PICU. We implemented a quality improvement bundle directed at ventilator-associated pneumonia in our PICU in 2005. We observed an increase in ventilator-associated tracheobronchitis coincident with the near-elimination of ventilator-associated pneumonia. The impact of ventilator-associated tracheobronchitis on critically ill children has not been previously described. Accordingly, we hypothesized that ventilator-associated tracheobronchitisis associated with increased length of stay, mortality, and hospital charge. DESIGN: Retrospective case-control study. PATIENTS: Critically ill children admitted to a quaternary PICU at a free-standing academic children's hospital in the United States. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective case control study, with institutional review board approval, of 77 consecutive cases of ventilator-associated tracheobronchitis admitted to our PICU from 2004-2010. We matched each case with a control based on the following criteria (in rank order): age range (< 30 d, 30 d to 24 mo, 24 mo to 12 yr, > 12 yr), admission Pediatric Risk of Mortality III score ± 10, number of ventilator days of control group (> 75% of days until development of ventilator-associated tracheobronchitis), primary diagnosis, underlying organ system dysfunction, surgical procedure, and gender. The primary outcome measured was PICU length of stay. Secondary outcomes included ventilator days, hospital length of stay, mortality, and PICU and hospital charges. Data was analyzed using chi square analysis and p less than 0.05 was considered significant. We successfully matched 45 of 77 ventilator-associated tracheobronchitis patients with controls. There were no significant differences in age, gender, diagnosis, or Pediatric Risk of Mortality III score between groups. Ventilator-associated tracheobronchitis patients had a longer PICU length of stay (median, 21.5 d, interquartile range, 24 d) compared to controls (median, 18 d; interquartile range, 17 d), although not statistically significant (p = 0.13). Ventilator days were also longer in the ventilator-associated tracheobronchitis patients (median, 17 d; IQR, 22 d) versus control (median, 10.5 d; interquartile range, 13 d) (p = 0.01). There was no significant difference in total hospital length of stay (54 d vs 36 d; p = 0.69). PICU mortality was higher in the ventilator-associated tracheobronchitis group (15% vs 5%; p = 0.14), although not statistically significant. There was an increase in both median PICU charges ($197,393 vs $172,344; p < 0.05) and hospital charges ($421,576 vs $350,649; p < 0.05) for ventilator-associated tracheobronchitis patients compared with controls. CONCLUSIONS: Ventilator-associated tracheobronchitis is a clinically significant hospital-acquired infection in the PICU and is associated with longer duration of mechanical ventilation and healthcare costs, possibly through causing a longer PICU length of stay. Quality improvement efforts should be directed at reducing the incidence of ventilator-associated tracheobronchitis in the PICU.

Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children.

Reliable prediction of severe acute kidney injury (AKI) has the potential to optimize treatment. Here we operationalized the empiric concept of renal angina with a renal angina index (RAI) and determined the predictive performance of RAI. This was assessed on admission to the pediatric intensive care unit, for subsequent severe AKI (over 200% rise in serum creatinine) 72 h later (Day-3 AKI). In a multicenter four cohort appraisal (one derivation and three validation), incidence rates for a Day 0 RAI of 8 or more were 15-68% and Day-3 AKI was 13-21%. In all cohorts, Day-3 AKI rates were higher in patients with an RAI of 8 or more with the area under the curve of RAI for predicting Day-3 AKI of 0.74-0.81. An RAI under 8 had high negative predictive values (92-99%) for Day-3 AKI. RAI outperformed traditional markers of pediatric severity of illness (Pediatric Risk of Mortality-II) and AKI risk factors alone for prediction of Day-3 AKI. Additionally, the RAI outperformed all KDIGO stages for prediction of Day-3 AKI. Thus, we operationalized the renal angina concept by deriving and validating the RAI for prediction of subsequent severe AKI. The RAI provides a clinically feasible and applicable methodology to identify critically ill children at risk of severe AKI lasting beyond functional injury. The RAI may potentially reduce capricious AKI biomarker use by identifying patients in whom further testing would be most beneficial.

Kidney-lung cross-talk and acute kidney injury.

There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney-lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI-ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid-base balance, and vascular tone. Experimental AKI research supports an "endocrine" role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney-lung crosstalk, the multiple pathways by which AKI affects kidney-lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a "balance of communication" that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm.

Acute kidney injury based on corrected serum creatinine is associated with increased morbidity in children following the arterial switch operation.

BACKGROUND AND OBJECTIVES: Evaluate risk factors for and impact of acute kidney injury on children following the arterial switch operation. DESIGN: Single-center retrospective chart review. SETTING: A tertiary children's hospital. PATIENTS: A total of 92 patients receiving the arterial switch operation from 1997 to 2008 at severe acute kidney injury was defined as a 100% serum creatinine rise over baseline. RESULTS: Of 92 patients, 18 (20%) developed severe acute kidney injury. Neither patient age or weight nor cardiopulmonary bypass time correlated with the development of acute kidney injury. Acute kidney injury was associated with the following: higher postoperative day 1 (POD1) fluid balance, higher inotrope scores (POD1 and POD2), and longer: postoperative ICU length of stay (p = 0.005), overall ICU length of stay (p = 0.05), and postoperative hospital length of stay (p = 0.006). The time to peak creatinine for acute kidney injury patients was between POD1 and POD2. Correction of serum creatinine for fluid balance increased the population defined as severe acute kidney injury and strengthened the association of acute kidney injury with postoperative morbidity. CONCLUSIONS: Acute kidney injury following the arterial switch operation is associated with increased morbidity. In this single center, single population, and homogenous cohort of patients, the development of acute kidney injury was not correlated with age, size, or cardiopulmonary bypass time, but was still associated with prolonged duration of ventilation and hospitalization. Notably, the failure to correct serum creatinine for fluid balance underestimates the prevalence and impact of acute kidney injury.

The Current State of Workforce Diversity and Inclusion in Pediatric Critical Care.

Literature suggests the pediatric critical care (PCC) workforce includes limited providers from groups underrepresented in medicine (URiM; African American/Black, Hispanic/Latinx, American Indian/Alaska Native, Native Hawaiian/Pacific Islander). Additionally, women and providers URiM hold fewer leadership positions regardless of health-care discipline or specialty. Data on sexual and gender minority representation and persons with different physical abilities within the PCC workforce are incomplete or unknown. More data are needed to understand the true landscape of the PCC workforce across disciplines. Efforts to increase representation, promote mentorship/sponsorship, and cultivate inclusivity must be prioritized to foster diversity and inclusion in PCC.

Renal angina: an emerging paradigm to identify children at risk for acute kidney injury.

Acute kidney injury (AKI) leads to high rates of morbidity and independently increases mortality risk. Therapy for AKI is likely limited by the inability to reliably diagnose AKI in its early stages, and, importantly, small changes in serum creatinine may be associated with poor outcomes and severe AKI. Whereas AKI biomarker research seeks to identify more sensitive and timely indices of kidney dysfunction, AKI lacks physical signs and symptoms to trigger biomarker assessment in at-risk patients, limiting biomarker efficacy. Accurate models of AKI prediction are unavailable. Severity of illness (SOI) scoring systems and organ dysfunction scores (OD), which stratify patients by prediction of mortality risk, are AKI reactive, not predictive. Kidney-specific severity scores do not account for AKI progression, and stratification models of AKI severity are not predictive of AKI. Thus, there is a need for a kidney scoring system that can help predict the development of AKI. This review highlights the concept of renal angina, a combination of patient risk factors and subtle AKI, as a methodology to predict AKI progression. Fulfillment of renal angina criteria will improve the efficiency of AKI prediction by biomarkers, in turn expediting early therapy and assisting in creation of AKI-predictive scoring systems.

Pediatric sepsis: preparing for the future against a global scourge.

Sepsis is a leading cause of morbidity and mortality among children worldwide. As consensus statements emerge regarding early recognition and goal-directed management of sepsis, scrutiny should be given to the unique characteristics of sepsis in children. Pediatric patients are not small adults! Sepsis epidemiology, pathophysiology, and management strategy can vary significantly from those for adults. Herein, we describe the epidemiology of pediatric sepsis, in both resource-rich and resource-poor worlds, and discuss how the pathophysiology of pediatric sepsis differs from that for adults. We discuss the timeline of management of pediatric sepsis, studying how discoveries over the past 50 years have changed the way sepsis is treated. Finally, we discuss the future of pediatric sepsis. We focus on approaches that carry the most substantive impact on the global burden of disease.