Surviving Sepsis Campaign Research Priorities 2023.

OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

The 2024 Pediatric Sepsis Challenge: Predicting In-Hospital Mortality in Children With Suspected Sepsis in Uganda.

The aim of this "Technical Note" is to inform the pediatric critical care data research community about the "2024 Pediatric Sepsis Data Challenge." This competition aims to facilitate the development of open-source algorithms to predict in-hospital mortality in Ugandan children with sepsis. The challenge is to first develop an algorithm using a synthetic training dataset, which will then be scored according to standard diagnostic testing criteria, and then be evaluated against a nonsynthetic test dataset. The datasets originate from admissions to six hospitals in Uganda (2017-2020) and include 3837 children, 6 to 60 months old, who were confirmed or suspected to have a diagnosis of sepsis. The synthetic dataset was created from a random subset of the original data. The test validation dataset closely resembles the synthetic dataset. The challenge should generate an optimal model for predicting in-hospital mortality. Following external validation, this model could be used to improve the outcomes for children with proven or suspected sepsis in low- and middle-income settings.

Core sepsis-related competencies for medical students: an international consensus by Delphi technique.

BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.

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.

Reducing the burden of preventable deaths from sepsis in Canada: A need for a national sepsis action plan.

Sepsis is a global health threat with significant morbidity and mortality. Despite clinical practice guidelines and developed health systems, sepsis is often unrecognized or misdiagnosed, leading to preventable harm. In Canada, sepsis is responsible for 1 in 20 deaths and is a significant driver of health system costs. Despite being a signatory to the World Health Organization's Resolution WHA 70.7, adopted in 2017, Canada has not lived up to its commitment. Many existing sepsis policies were developed in response to a specific tragedy, and there is no national sepsis action plan. In this article, we describe the burden of sepsis, provide examples of existing, context-specific, reactionary sepsis policies, and urge a coordinated, proactive Canadian sepsis action plan to reduce the burden of sepsis.

Risk factors for postpartum maternal mortality and hospital readmission in low- and middle-income countries: a systematic review.

BACKGROUND: In low- and middle-income countries, approximately two thirds of maternal deaths occur in the postpartum period. Yet, care for women beyond 24 h after discharge is limited. The objective of this systematic review is to summarize current evidence on socio-demographic and clinical risk factors for (1) postpartum mortality and (2) postpartum hospital readmission. METHODS: A combination of keywords and subject headings (i.e. MeSH terms) for postpartum maternal mortality or readmission were searched. Articles published up to January 9, 2021 were identified in MEDLINE, EMBASE, and CINAHL databases, without language restrictions. Studies reporting socio-demographic or clinical risk factors for postpartum mortality or readmission within six weeks of delivery among women who delivered a livebirth in a low- or middle-income country were included. Data were extracted independently by two reviewers based on study characteristics, population, and outcomes. Included studies were assessed for quality and risk of bias using the Downs and Black checklist for ratings of randomized and non-randomized studies. RESULTS: Of 8783 abstracts screened, seven studies were included (total N = 387,786). Risk factors for postpartum mortality included Caesarean mode of delivery, nulliparity, low or very low birthweight, and shock upon admission. Risk factors for postpartum readmission included Caesarean mode of delivery, HIV positive serostatus, and abnormal body temperature. CONCLUSIONS: Few studies reported individual socio-demographic or clinical risk factors for mortality or readmission after delivery in low- and middle-income countries; only Caesarean delivery was consistently reported. Further research is needed to identify factors that put women at greatest risk of post-discharge complications and mortality. Understanding post-discharge risk would facilitate targeted postpartum care and reduce adverse outcomes in women after delivery. TRIAL REGISTRATION: PROSPERO registration number: CRD42018103955.

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.

The Return on Investment of a Province-Wide Quality Improvement Initiative for Reducing In-Hospital Sepsis Rates and Mortality in British Columbia, Canada.

OBJECTIVES: Sepsis is a life-threatening medical emergency. There is a paucity of information on whether quality improvement approaches reduce the in-hospital sepsis caseload or save lives and decrease the healthcare system and society's cost at the provincial/national levels. This study aimed to assess the outcomes and economic impact of a province-wide quality improvement initiative in Canada. DESIGN: Retrospective population-based study with interrupted time series and return on investment analyses. SETTING: The sepsis cases and deaths averted over time for British Columbia were calculated and compared with the rest of Canada (excluding Quebec and three territories). PATIENTS: Aggregate data were obtained from the Canadian Institute for Health Information on risk-adjusted in-hospital sepsis rates and sepsis mortality in acute care sites across Canada. INTERVENTIONS: In 2012, the British Columbia Sepsis Network was formed to reduce sepsis occurrence and mortality through education, knowledge translation, and quality improvement. MEASUREMENTS AND MAIN RESULTS: A return on investment analysis compared the financial investment for the British Columbia Sepsis Network with the savings from averted sepsis occurrence and mortality. An estimated 981 sepsis cases and 172 deaths were averted in the post-British Columbia Sepsis Network period (2014-2018). The total cost, including the development and implementation of British Columbia Sepsis Network, was $449,962. Net savings due to cases averted after program costs were considered were $50.6 million in 2018. This translates into a return of $112.5 for every dollar invested. CONCLUSIONS: British Columbia Sepsis Network appears to have averted a greater number of sepsis cases and deaths in British Columbia than the national average and yielded a positive return on investment. Our findings strengthen the policy argument for targeted quality improvement initiatives for sepsis care and provide a model of care for other provinces in Canada and elsewhere globally.

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.

Health worker perspectives of Smart Triage, a digital triaging platform for quality improvement at a referral hospital in Uganda: a qualitative analysis.

BACKGROUND: Effective triage at hospitals can improve outcomes for children globally by helping identify and prioritize care for those most at-risk of death. Paper-based pediatric triage guidelines have been developed to support frontline health workers in low-resource settings, but these guidelines can be challenging to implement. Smart Triage is a digital triaging platform for quality improvement (QI) that aims to address this challenge. Smart Triage represents a major cultural and behavioural shift in terms of managing patients at health facilities in low-and middle-income countries. The purpose of this study is to understand user perspectives on the usability, feasibility, and acceptability of Smart Triage to inform ongoing and future implementation. METHODS: This was a descriptive qualitative study comprising of face-to-face interviews with health workers (n = 15) at a regional referral hospital in Eastern Uganda, conducted as a sub-study of a larger clinical trial to evaluate Smart Triage (NCT04304235). Thematic analysis was used to assess the usability, feasibility, and acceptability of the platform, focusing on its use in stratifying and prioritizing patients according to their risk and informing QI initiatives implemented by health workers. RESULTS: With appropriate training and experience, health workers found most features of Smart Triage usable and feasible to implement, and reported the platform was acceptable due to its positive impact on reducing the time to treatment for emergency pediatric cases and its use in informing QI initiatives within the pediatric ward. Several factors that reduced the feasibility and acceptability were identified, including high staff turnover, a lack of medical supplies at the hospital, and challenges with staff attitudes. CONCLUSION: Health workers can use the Smart Triage digital triaging platform to identify and prioritize care for severely ill children and improve quality of care at health facilities in low-resource settings. Future innovation is needed to address identified feasibility and acceptability challenges; however, this platform could potentially address some of the challenges to implementing current paper-based systems.

A 2-Phase Survey to Assess a Facility's Readiness for Pediatric Essential Emergency and Critical Care in Resource-Limited Settings: A Literature Review and Survey Development.

OBJECTIVE: Infectious diseases, including pneumonia, malaria, and diarrheal diseases, are the leading causes of death in children younger than 5 years worldwide. The vast majority of these deaths occur in resource-limited settings where there is significant variation in the availability and type of human, physical, and infrastructural resources. The ability to identity gaps in healthcare systems that may hinder their ability to deliver care is an important step to determining specific interventions for quality improvement. Our study objective was to develop a comprehensive, digital, open-access health facility survey to assess facility readiness to provide pediatric critical care in resource-limited settings (eg, low- and lower middle-income countries). METHODS: A literature review of existing facility assessment tools and global guidelines was conducted to generate a database of survey questions. These were then mapped to one of the following 8 domains: hospital statistics, services offered, operational flow, facility infrastructure, staff and training, medicines and equipment, diagnostic capacity, and quality of clinical care. A 2-phase survey was developed and an iterative review process of the survey was undertaken with 12 experts based in low- and middle-income countries. This was built into the REDCap Mobile Application for electronic data capture. RESULTS: The literature review process yielded 7 facility assessment tools and 7 global guidelines for inclusion. After the iterative review process, the final survey consisted of 11 sections with 457 unique questions in the first phase, "environmental scan," focusing on the infrastructure, availability, and functionality of resources, and 3 sections with 131 unique questions in the second phase, "observation scan," focusing on the level of clinical competency. CONCLUSIONS: A comprehensive 2-phase survey was created to evaluate facility readiness for pediatric critical care. Results will assist hospital administrators and policymakers to determine priority areas for quality improvement, enabling them to implement a Plan-Do-Study-Act cycle to improve care for the critically ill child.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017. METHODS: We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990-2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates. FINDINGS: In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9-62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1-12·0) sepsis-related deaths were reported, representing 19·7% (18·2-21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8-54·5) and mortality decreased by 52·8% (47·7-57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia. INTERPRETATION: Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa. FUNDING: The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.

The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness.

OBJECTIVES: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. DESIGN: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. METHODS: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. RESULTS: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? CONCLUSIONS: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019.

Vasopressor Therapy in the Intensive Care Unit.

After fluid administration for vasodilatory shock, vasopressors are commonly infused. Causes of vasodilatory shock include septic shock, post-cardiovascular surgery, post-acute myocardial infarction, postsurgery, other causes of an intense systemic inflammatory response, and drug -associated anaphylaxis. Therapeutic vasopressors are hormones that activate receptors-adrenergic: α1, α2, ß1, ß2; angiotensin II: AG1, AG2; vasopressin: AVPR1a, AVPR1B, AVPR2; dopamine: DA1, DA2. Vasopressor choice and dose vary widely because of patient and physician practice heterogeneity. Vasopressor adverse effects are excessive vasoconstriction causing organ ischemia/infarction, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. To date, no randomized controlled trial (RCT) of vasopressors has shown a decreased 28-day mortality rate. There is a need for evidence regarding alternative vasopressors as first-line vasopressors. We emphasize that vasopressors should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in shock with vasodilation. Norepinephrine is the first-choice vasopressor in septic and vasodilatory shock. Interventions that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality significantly. In patients not responsive to norepinephrine, vasopressin or epinephrine may be added. Angiotensin II may be useful for rapid resuscitation of profoundly hypotensive patients. Inotropic agent(s) (e.g., dobutamine) may be needed if vasopressors decrease ventricular contractility. Dopamine has fallen to almost no-use recommendation because of adverse effects; angiotensin II is available clinically; there are potent vasopressors with scant literature (e.g., methylene blue); and the novel V1a agonist selepressin missed on its pivotal RCT primary outcome. In pediatric septic shock, vasopressors, epinephrine, and norepinephrine are recommended equally because there is no clear evidence that supports the use of one vasoactive agent. Dopamine is recommended when epinephrine or norepinephrine is not available. New strategies include perhaps patients will be started on several vasopressors with complementary mechanisms of action, patients may be selected for particular vasopressors according to predictive biomarkers, and novel vasopressors may emerge with fewer adverse effects.

Variability in the Hemodynamic Response to Fluid Bolus in Pediatric Septic Shock.

OBJECTIVES: Fluid boluses are commonly administered to improve the cardiac output and tissue oxygen delivery in pediatric septic shock. The objective of this study is to evaluate the effect of an early fluid bolus administered to children with septic shock on the cardiac index and mean arterial pressure, as well as on the hemodynamic response and its relationship with outcome. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: We prospectively collected hemodynamic data from children with septic shock presenting to the emergency department or the PICU who received a fluid bolus (10 mL/kg of Ringers Lactate over 30 min). A clinically significant response in cardiac index-responder and mean arterial pressure-responder was both defined as an increase of greater than or equal to 10% 10 minutes after fluid bolus. MEASUREMENTS AND MAIN RESULTS: Forty-two children with septic shock, 1 month to 16 years old, median Pediatric Risk of Mortality-III of 13 (interquartile range, 9-19), of whom 66% were hypotensive and received fluid bolus within the first hour of shock recognition. Cardiac index- and mean arterial pressure-responsiveness rates were 31% and 38%, respectively. We failed to identify any association between cardiac index and mean arterial pressure changes (r = 0.203; p = 0.196). Cardiac function was similar in mean arterial pressure- and cardiac index-responders and nonresponders. Mean arterial pressure-responders increased systolic, diastolic, and perfusion pressures (mean arterial pressure - central venous pressure) after fluid bolus due to higher indexed systemic vascular resistance and arterial elastance index. Mean arterial pressure-nonresponders required greater vasoactive-inotrope support and had higher mortality. CONCLUSIONS: The hemodynamic response to fluid bolus in pediatric septic shock was variable and unpredictable. We failed to find a relationship between mean arterial pressure and cardiac index changes. The adverse effects of fluid bolus extended beyond fluid overload and, in some cases, was associated with reduced mean arterial pressure, perfusion pressures and higher vasoactive support. Mean arterial pressure-nonresponders had increased mortality. The response to the initial fluid bolus may be helpful to understand each patient's individualized physiologic response and guide continued hemodynamic management.

Simulation and Active Learning Decreases Training Time of an Emergency Triage Assessment and Treatment Course in Pilot Study in Malawi: Implications for Increasing Efficiency and Workforce Capacity in Low-Resource Settings.

OBJECTIVES: The aim of the Emergency Triage Assessment and Treatment (ETAT) plus trauma course is to improve the quality of care provided to infants and children younger than 5 years. The curriculum was revised and shortened from 5 to 2.5 days by enhancing simulation and active learning opportunities. The aim of this study was to examine the feasibility and value of the new short-form ETAT course by assessing postcourse knowledge and satisfaction. METHODS: We delivered the short-form ETAT course to a group of interdisciplinary health workers in Malawi. Precourse and postcourse knowledge was assessed using a standardized 20 questions short answer test used previously in the 5-day courses. A 13-statement survey with 2 open-ended questions was used to examine participant satisfaction. RESULTS: Participants' postcourse knowledge improved significantly (P < 0.001) after the shorter ETAT course. Participants reported high levels of satisfaction with the short-form ETAT. CONCLUSIONS: Simulation and other active learning strategies reduced training time by 50% in the short-form ETAT course. Participants with and without previous ETAT training improved their knowledge after participating in the short-form ETAT course. Reduced training time is beneficial in settings already burdened by scarce human resources, may facilitate better access to in-service training, and build capacity while conserving resources in low-resource settings.

Diagnosis and Acute Management of COVID-19 and Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Most children with coronavirus disease 2019 (COVID-19) infection are asymptomatic or have mild disease. About 5% of infected children will develop severe or critical disease. Rapid identification and treatment are essential for children who are critically ill with signs and symptoms of respiratory failure, septic shock, and multisystem inflammatory syndrome in children. This article is intended for pediatricians, pediatric emergency physicians, and individuals involved in the emergency care of children. It reviews the current epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, summarizes key aspects of clinical assessment including identification of high-risk patients and manifestations of severe disease, and provides an overview of COVID-19 management in the emergency department based on clinical severity.

How Are Clinicians Treating Children With Sepsis in Emergency Departments in Latin America?: An International Multicenter Survey.

OBJECTIVE: Guidelines adherence in emergency departments (EDs) relies partly on the availability of resources to improve sepsis care and outcomes. Our objective was to assess the management of pediatric septic shock (PSS) in Latin America's EDs and to determine the impact of treatment coordinated by a pediatric emergency specialist (PEMS) versus nonpediatric emergency specialists (NPEMS) on guidelines adherence. METHODS: Prospective, descriptive, and multicenter study using an electronic survey administered to PEMS and NPEMS who treat PSS in EDs in 14 Latin American countries. RESULTS: We distributed 2164 surveys with a response rate of 41.5%, of which 22.5% were PEMS. Overall American College of Critical Care Medicine reported guidelines adherence was as follows: vascular access obtained in 5 minutes, 76%; fluid infusion technique, 60%; administering 40 to 60 mL/kg within 30 minutes, 32%; inotropic infusion by peripheral route, 61%; dopamine or epinephrine in cold shock, 80%; norepinephrine in warm shock, 57%; and antibiotics within 60 minutes, 82%. Between PEMS and NPEMS, the following differences were found: vascular access in 5 minutes, 87.1% versus 72.7% (P < 0.01); fluid infusion technique, 72.3% versus 55.9% (P < 0.01); administering 40 to 60 mL/kg within 30 minutes, 42% versus 29% (P < 0.01); inotropic infusion by peripheral route, 75.7% versus 56.3% (P < 0.01); dopamine or epinephrine in cold shock, 87.1% versus 77.3% (P < 0.05); norepinephrine in warm shock, 67.8% versus 54% (P < 0.01); and antibiotic administration within first 60 minutes, 90.1% versus 79.3% (P < 0.01), respectively. Good adherence criteria were followed by 24%. The main referred barrier for sepsis care was a failure in its recognition, including the lack of triage tools. CONCLUSIONS: In some Latin American countries, there is variability in self-reported adherence to the evidence-based recommendations for the treatment of PSS during the first hour. The coordination by PEMS support greater adherence to these recommendations.