Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis.

Importance: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. Objective: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. Design, Setting, and Participants: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. Exposure: The number of minutes from emergency department arrival to antibiotic administration. Main Outcomes and Measures: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. Results: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. Conclusions and Relevance: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Bundled Care to Reduce Sepsis Mortality: The Improving Pediatric Sepsis Outcomes (IPSO) Collaborative.

OBJECTIVES: We sought to improve utilization of a sepsis care bundle and decrease 3- and 30- day sepsis-attributable mortality, as well as determine which care elements of a sepsis bundle are associated with improved outcomes. METHODS: Children's Hospital Association formed a QI collaborative to Improve Pediatric Sepsis Outcomes (IPSO) (January 2017-March 2020 analyzed here). IPSO Suspected Sepsis (ISS) patients were those without organ dysfunction where the provider "intended to treat" sepsis. IPSO Critical Sepsis (ICS) patients approximated those with septic shock. Process (bundle adherence), outcome (mortality), and balancing measures were quantified over time using statistical process control. An original bundle (recognition method, fluid bolus < 20 min, antibiotics < 60 min) was retrospectively compared with varying bundle time-points, including a modified evidence-based care bundle, (recognition method, fluid bolus < 60 min, antibiotics < 180 min). We compared outcomes using Pearson χ-square and Kruskal Wallis tests and adjusted analysis. RESULTS: Reported are 24 518 ISS and 12 821 ICS cases from 40 children's hospitals (January 2017-March 2020). Modified bundle compliance demonstrated special cause variation (40.1% to 45.8% in ISS; 52.3% to 57.4% in ICS). The ISS cohort's 30-day, sepsis-attributable mortality dropped from 1.4% to 0.9%, a 35.7% relative reduction over time (P < .001). In the ICS cohort, compliance with the original bundle was not associated with a decrease in 30-day sepsis-attributable mortality, whereas compliance with the modified bundle decreased mortality from 4.75% to 2.4% (P < .01). CONCLUSIONS: Timely treatment of pediatric sepsis is associated with reduced mortality. A time-liberalized care bundle was associated with greater mortality reductions.

Characteristics and Outcomes of Sepsis Presenting in Inpatient Pediatric Settings.

OBJECTIVE: The pediatric sepsis literature lacks studies examining the inpatient setting, yet sepsis remains a leading cause of death in children's hospitals. More information is needed about sepsis arising in patients already hospitalized to improve morbidity and mortality outcomes. This study describes the clinical characteristics, process measures, and outcomes of inpatient sepsis cases compared with emergency department (ED) sepsis cases within the Improving Pediatric Sepsis Outcomes data registry from 46 hospitals that care for children. METHODS: This retrospective cohort study included Improving Pediatric Sepsis Outcomes sepsis cases from January 2017 to December 2019 with onset in inpatient or ED. We used descriptive statistics to compare inpatient and ED sepsis metrics and describe inpatient sepsis outcomes. RESULTS: The cohort included 26 855 cases; 8.4% were inpatient and 91.6% were ED. Inpatient cases had higher sepsis-attributable mortality (2.0% vs 1.4%, P = .025), longer length of stay after sepsis recognition (9 vs 5 days, P <.001), more intensive care admissions (57.6% vs 54.1%, P = .002), and greater average vasopressor use (18.0% vs 13.6%, P <.001) compared with ED. In the inpatient cohort, >40% of cases had a time from arrival to recognition within 12 hours. In 21% of cases, this time was >96 hours. Improved adherence to sepsis treatment bundles over time was associated with improved 30-day sepsis-attributable mortality for inpatients with sepsis. CONCLUSIONS: Inpatient sepsis cases had longer lengths of stay, more need for intensive care, and higher vasopressor use. Sepsis-attributable mortality was significantly higher in inpatient cases compared with ED cases and improved with improved sepsis bundle adherence.

Intravenous Fluid Bolus Rates Associated with Outcomes in Pediatric Sepsis: A Multi-Center Analysis.

Purpose: Pediatric sepsis guidelines recommend rapid intravenous fluid (IVF) bolus administration rates (BAR). Recent sepsis studies suggest that rapid BAR may be associated with increased morbidity. We aimed to describe the association between emergency department (ED) IVF BAR and clinical outcomes in pediatric sepsis. Patients and Methods: Secondary post-hoc analysis of retrospective cohort data from 19 hospitals in the Pediatric Septic Shock Collaborative (PSSC) database. Patients with presumed septic shock were defined by severe sepsis/septic shock diagnostic codes, receipt of septic shock therapies, or floor-to-ICU transfers within 12 hours from ED admission for septic shock. Patients (2 months-21 years) with complete data on weight, antibiotic receipt, bolus timing, and bolus volumes were included. The primary outcome was 30-day mortality. Associations between BAR and mortality and secondary (intubation or non-invasive positive pressure ventilation = NIPPV) outcomes were assessed using unadjusted and adjusted logistic regression. Results: The PSSC database included 6731 patients; 3969 met inclusion and received a median ED volume of 40.2 mL/kg. Seventy-six (1.9%) patients died, 151 (3.8%) were intubated, and 235 (5.9%) had NIPPV administered. The median BAR was 25.7 mL/kg/hr. For each 20 mL/kg/hr increase in BAR, the adjusted odds ratio (aOR) for 30-day mortality [aOR = 1.11 (95% CI 1.01, 1.23)], intubation [aOR = 1.25 (95% CI 1.09, 1.44)], and NIPPV [aOR = 1.20 (95% CI 1.05, 1.38)] significantly increased. Conclusion: Faster ED IVF bolus administration rates in this pediatric sepsis database were associated with higher adjusted odds of death, intubation and NIPPV. Controlled trials are needed to determine if these associations are replicable.

Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock.

STUDY OBJECTIVE: To determine whether the receipt of more than or equal to 30 mL/kg of intravenous fluid in the first hour after emergency department (ED) arrival is associated with sepsis-attributable mortality among children with hypotensive septic shock. METHODS: This is a retrospective cohort study set in 57 EDs in the Improving Pediatric Sepsis Outcomes quality improvement collaborative. Patients less than 18 years of age with hypotensive septic shock who received their first intravenous fluid bolus within 1 hour of arrival at the ED were propensity-score matched for probability of receiving more than or equal to 30 mL/kg in the first hour. Sepsis-attributable mortality was compared. We secondarily evaluated the association between the first-hour fluid volume and sepsis-attributable mortality in all children with suspected sepsis in the first hour after arrival at the ED, regardless of blood pressure. RESULTS: Of the 1,982 subjects who had hypotensive septic shock and received a first fluid bolus within 1 hour of arrival at the ED, 1,204 subjects were propensity matched. In the matched patients receiving more than or equal to 30 mL/kg of fluid, 26 (4.3%) of 602 subjects had 30-day sepsis-attributable mortality compared with 25 (4.2%) of 602 receiving less than 30 mL/kg (odds ratio 1.04, 95% confidence interval 0.59 to 1.83). Among the patients with suspected sepsis regardless of blood pressure, 30-day sepsis-attributable mortality was 3.0% in those receiving more than or equal to 30 mL/kg versus 2.0% in those receiving less than 30 ml/kg (odds ratio 1.52, 95% confidence interval 0.95 to 2.44.) CONCLUSION: In children with hypotensive septic shock receiving a timely first fluid bolus within the first hour of ED care, receiving more than or equal to 30 mL/kg of bolus intravenous fluids in the first hour after arrival at the ED was not associated with mortality compared with receiving less than 30 mL/kg.

Pediatric Septic Shock Collaborative Improves Emergency Department Sepsis Care in Children.

OBJECTIVES: The pediatric emergency department (ED)-based Pediatric Septic Shock Collaborative (PSSC) aimed to improve mortality and key care processes among children with presumed septic shock. METHODS: This was a multicenter learning and improvement collaborative of 19 pediatric EDs from November 2013 to May 2016 with shared screening and patient identification recommendations, bundles of care, and educational materials. Process metrics included minutes to initial vital sign assessment and to first and third fluid bolus and antibiotic administration. Outcomes included 3- and 30-day all-cause in-hospital mortality, hospital and ICU lengths of stay, hours on increased ventilation (including new and increases from chronic baseline in invasive and noninvasive ventilation), and hours on vasoactive agent support. Analysis used statistical process control charts and included both the overall sample and an ICU subgroup. RESULTS: Process improvements were noted in timely vital sign assessment and receipt of antibiotics in the overall group. Timely first bolus and antibiotics improved in the ICU subgroup. There was a decrease in 30-day all-cause in-hospital mortality in the overall sample. CONCLUSIONS: A multicenter pediatric ED improvement collaborative showed improvement in key processes for early sepsis management and demonstrated that a bundled quality improvement-focused approach to sepsis management can be effective in improving care.

Metric Development for the Multicenter Improving Pediatric Sepsis Outcomes (IPSO) Collaborative.

BACKGROUND: A 56 US hospital collaborative, Improving Pediatric Sepsis Outcomes, has developed variables, metrics and a data analysis plan to track quality improvement (QI)-based patient outcomes over time. Improving Pediatric Sepsis Outcomes expands on previous pediatric sepsis QI efforts by improving electronic data capture and uniformity across sites. METHODS: An expert panel developed metrics and corresponding variables to assess improvements across the care delivery spectrum, including the emergency department, acute care units, hematology and oncology, and the ICU. Outcome, process, and balancing measures were represented. Variables and statistical process control charts were mapped to each metric, elucidating progress over time and informing plan-do-study-act cycles. Electronic health record (EHR) abstraction feasibility was prioritized. Time 0 was defined as time of earliest sepsis recognition (determined electronically), or as a clinically derived time 0 (manually abstracted), identifying earliest physiologic onset of sepsis. RESULTS: Twenty-four evidence-based metrics reflected timely and appropriate interventions for a uniformly defined sepsis cohort. Metrics mapped to statistical process control charts with 44 final variables; 40 could be abstracted automatically from multiple EHRs. Variables, including high-risk conditions and bedside huddle time, were challenging to abstract (reported in <80% of encounters). Size or type of hospital, method of data abstraction, and previous QI collaboration participation did not influence hospitals' abilities to contribute data. To date, 90% of data have been submitted, representing 200 007 sepsis episodes. CONCLUSIONS: A comprehensive data dictionary was developed for the largest pediatric sepsis QI collaborative, optimizing automation and ensuring sustainable reporting. These approaches can be used in other large-scale sepsis QI projects in which researchers seek to leverage EHR data abstraction.

Development of a Quality Improvement Learning Collaborative to Improve Pediatric Sepsis Outcomes.

Pediatric sepsis is a major public health problem. Published treatment guidelines and several initiatives have increased adherence with guideline recommendations and have improved patient outcomes, but the gains are modest, and persistent gaps remain. The Children's Hospital Association Improving Pediatric Sepsis Outcomes (IPSO) collaborative seeks to improve sepsis outcomes in pediatric emergency departments, ICUs, general care units, and hematology/oncology units. We developed a multicenter quality improvement learning collaborative of US children's hospitals. We reviewed treatment guidelines and literature through 2 in-person meetings and multiple conference calls. We defined and analyzed baseline sepsis-attributable mortality and hospital-onset sepsis and developed a key driver diagram (KDD) on the basis of treatment guidelines, available evidence, and expert opinion. Fifty-six hospital-based teams are participating in IPSO; 100% of teams are engaged in educational and information-sharing activities. A baseline, sepsis-attributable mortality of 3.1% was determined, and the incidence of hospital-onset sepsis was 1.3 cases per 1000 hospital admissions. A KDD was developed with the aim of reducing both the sepsis-attributable mortality and the incidence of hospital-onset sepsis in children by 25% from baseline by December 2020. To accomplish these aims, the KDD primary drivers focus on improving the following: treatment of infection; recognition, diagnosis, and treatment of sepsis; de-escalation of unnecessary care; engagement of patients and families; and methods to optimize performance. IPSO aims to improve sepsis outcomes through collaborative learning and reliable implementation of evidence-based interventions.

Evaluating Pediatric Sepsis Definitions Designed for Electronic Health Record Extraction and Multicenter Quality Improvement.

OBJECTIVES: To describe the Children's Hospital Association's Improving Pediatric Sepsis Outcomes sepsis definitions and the identified patients; evaluate the definition using a published framework for evaluating sepsis definitions. DESIGN: Observational cohort. SETTING: Multicenter quality improvement collaborative of 46 hospitals from January 2017 to December 2018, excluding neonatal ICUs. PATIENTS: Improving Pediatric Sepsis Outcomes Sepsis was defined by electronic health record evidence of suspected infection and sepsis treatment or organ dysfunction. A more severely ill subgroup, Improving Pediatric Sepsis Outcomes Critical Sepsis, was defined, approximating septic shock. INTERVENTIONS: Participating hospitals identified patients, extracted data, and transferred de-identified data to a central data warehouse. The definitions were evaluated across domains of reliability, content validity, construct validity, criterion validity, measurement burden, and timeliness. MEASUREMENTS AND MAIN RESULTS: Forty hospitals met data quality criteria across four electronic health record platforms. There were 23,976 cases of Improving Pediatric Sepsis Outcomes Sepsis, including 8,565 with Improving Pediatric Sepsis Outcomes Critical Sepsis. The median age was 5.9 years. There were 10,316 (43.0%) immunosuppressed or immunocompromised patients, 4,135 (20.3%) with central lines, and 2,352 (11.6%) chronically ventilated. Among Improving Pediatric Sepsis Outcomes Sepsis patients, 60.8% were admitted to intensive care, 26.4% had new positive-pressure ventilation, and 19.7% received vasopressors. Median hospital length of stay was 6.0 days (3.0-13.0 d). All-cause 30-day in-hospital mortality was 958 (4.0%) in Improving Pediatric Sepsis Outcomes Sepsis; 541 (6.3%) in Improving Pediatric Sepsis Outcomes Critical Sepsis. The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated strengths in content validity, convergent construct validity, and criterion validity; weakness in reliability. Improving Pediatric Sepsis Outcomes Sepsis definitions had significant initial measurement burden (median time from case completion to submission: 15 mo [interquartile range, 13-18 mo]); timeliness improved once data capture was established (median, 26 d; interquartile range, 23-56 d). CONCLUSIONS: The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated feasibility for large-scale data abstraction. The patients identified provide important information about children treated for sepsis. When operationalized, these definitions enabled multicenter identification and data aggregation, indicating practical utility for quality improvement.

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Timing of Antibiotic Administration in Pediatric Sepsis.

OBJECTIVES: Antibiotic administration within 1 hour of hypotension has been shown to reduce mortality. It is unknown whether antibiotics before hypotension in children who eventually meet criteria for septic shock improves outcomes. This study assesses whether antibiotic timing from the time of meeting criteria for sepsis in children with septic shock impacts morbidity and mortality. METHODS: This is a retrospective study of children 18 years or younger presenting to a tertiary free-standing children's hospital emergency department with sepsis that subsequently progressed to septic shock and were admitted to an intensive care unit from 2008 to 2012. The time when the patient met criteria for sepsis to the time of first antibiotic administration was assessed and correlated with patient morbidity and mortality. RESULTS: Among 135 children (median age, 13.1 years), 34 (25%) were previously healthy, whereas 49 (36%) had 2 or more medical comorbidities. Twenty-seven children (20%) had positive blood cultures, 17 (13%) had positive urine cultures, and 34 (25%) had chest x-ray findings that were interpreted as pneumonia. Among the 42 (31%) with antibiotics within 1 hour from criteria for sepsis, there was higher mortality (4/42 vs 0/93, P = 0.009), more organ dysfunction, longer time on a vasoactive infusion, and increased intensive care unit and hospital lengths of stay (all P < 0.05). CONCLUSIONS: Children with criteria for sepsis who subsequently progressed to septic shock who received antibiotics within 1 hour of meeting sepsis criteria had increased mortality, length of stay, and organ dysfunction.

Recognition, Diagnostics, and Management of Pediatric Severe Sepsis and Septic Shock in the Emergency Department.

Several new studies have emerged in recent years that have attempted to aid emergency department providers in recognizing and treating pediatric patients with severe sepsis and septic shock. National guidelines and supporting literature are unanimous in recommendations that early recognition and timely therapeutics are necessary for improved survival and decreased morbidity. The literature is less concrete in defining how emerging advances in the field can aid in time-sensitive care of these patients. This article summarizes the recent literature as it pertains to the initial presentation of severe sepsis and septic shock in the pediatric patient within the emergency department.

A Quality Improvement Collaborative for Pediatric Sepsis: Lessons Learned.

BACKGROUND: Sepsis is a leading cause of morbidity and mortality in children worldwide. Barriers exist for timely recognition and management in emergency care settings. This 1-year quality improvement collaborative sought to reduce mortality from sepsis. METHODS: Fifteen hospitals participated initially. We included children with a spectrum of illness from sepsis to septic shock. The intervention bundle focused on recognition, escalation of care, and the first hour of resuscitation. We conducted monthly learning sessions and disseminated data reports of site-specific and aggregated metrics to drive rapid cycle improvement. RESULTS: Seven sites contributed enough data to be analyzed. Of the 1,173 pediatric patients in the total cohort, 506 presented with severe sepsis/septic shock. Quarterly data demonstrated a mean improvement in initial clinical assessment from 46% to 60% (P < 0.001) and in adherence to the administration of first fluid bolus within 15 minutes from 38% to 46% (P < 0.015). There was no statistically significant improvement in other process metrics. There was no statistically significant improvement in mortality for the total cohort (sepsis to septic shock) or either of the subgroups in either 3- or 30-day mortality. CONCLUSIONS: A quality improvement collaborative focused on improving timely recognition and management of pediatric sepsis to septic shock led to some process improvements but did not show improvement in mortality. Future national efforts should standardize definitions and processes of care for sepsis to septic shock, including the identification of a "time zero" for measuring the timeliness of treatment.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock." DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006-2014). The PubMed/Medline/Embase literature (2006-14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution-specific use of 1) a "recognition bundle" containing a trigger tool for rapid identification of patients with septic shock, 2) a "resuscitation and stabilization bundle" to help adherence to best practice principles, and 3) a "performance bundle" to identify and overcome perceived barriers to the pursuit of best practice principles.