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Background Following the publication of 2014 consensus statement regarding mass critical care during public health emergencies, much has been learned about surge responses and the care of overwhelming numbers of patients during the COVID-19 pandemic.1 Gaps in prior pandemic planning were identified and require modification in the midst of ongoing surge throughout the world. Methods The Task Force for Mass Critical Care (TFMCC) adopted a modified version of established rapid guideline methodologies from the World Health Organization2 and the Guidelines International Network-McMaster Guideline Development Checklist.3 With a consensus development process incorporating expert opinion to define important questions and extract evidence, TFMCC developed relevant pandemic surge suggestions in a structured manner, incorporating peer-reviewed literature, “gray” evidence from lay media sources, and anecdotal experiential evidence. Results Ten suggestions were identified regarding staffing, load-balancing, communication, and technology. Staffing models are suggested with resilience strategies to support critical care staff. Intensive care unit (ICU) surge strategies and strain indicators are suggested to enhance ICU prioritization tactics to maintain contingency level care and avoid crisis triage, with early transfer strategies to further load-balance care. We suggest intensivists and hospitalists be engaged with the incident command structure to ensure two-way communication, situational awareness, and the use of technology to support critical care delivery and families of patients in intensive care units (ICUs). Conclusions A subcommittee from the Task Force for Mass Critical Care offers interim evidence-informed operational strategies to assist hospitals and communities to plan for and respond to surge capacity demands from COVID-19.

Supplemental Digital Content is available in the text., 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.

This article reviews the many factors that have to be taken into account as we consider the advancement of pediatric critical care (PCC) in multiple settings across the world. The extent of PCC and the range of patients who are cared for in this environment are considered. Along with a review of the ongoing treatment and technology advances in the PCC setting, the structures and systems required to support these services are also considered. Finally the question of how PCC can be made sustainable in a volatile world with the impacts of global crises such as climate change is addressed.

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.

Background Early in the COVID-19 pandemic, there was serious concern that the United States (US) would encounter a short fall of mechanical ventilators. In response, the US government, utilizing the Defense Production Act ordered the development of 200,000 ventilators from 11 different manufacturers. These ventilators have different capabilities and it is not evident whether all are able to support COVID-19 patients. Research question Evaluate ventilator requirements for affected COVID-19 patients, assess the clinical performance of current SNS ventilators employed during the pandemic, and finally compare ordered ventilators functionality based on COVID-19 patient needs. Study design and methods Current published literature, publicly available documents, and lay press articles were reviewed by a diverse team of disaster experts. Data was assembled into tabular format which formed the basis for analysis and future recommendations. Results COVID-19 patients often develop severe hypoxemic acute respiratory failure and ARDS requiring high levels of ventilator support. Current SNS ventilators were unable to fully support all COVID-19 patients, and only about half of newly ordered ventilators have the capacity to support the most severely affected patients; ventilators with less capacity for providing high level support are still of significant value in caring for many patients. Interpretation Current SNS ventilators and those on order are capable of supporting most but not all COVID-19 patients. Technologic, logistic, and educational challenges encountered from current SNS ventilators are summarized, with potential next generation SNS ventilator updates offered. Clinical trial registration N/A.

Objectives To use electronic health record data from the first 2 hours of care to derive and validate a model to predict hypotensive septic shock in children with infection. Design Derivation-validation study using an existing registry. Setting Six emergency care sites within a regional pediatric healthcare system. Three datasets of unique visits were designated:1)training set (five sites, April 1, 2013, to December 31, 2016),2)temporal test set (five sites, January 1, 2017, to June 30, 2018), and3)geographic test set (sixth site, April 1, 2013, to June 30, 2018). Patients Patients in whom clinicians were concerned about serious infection from 60 days to 18 years were included; those with septic shock in the first 2 hours were excluded. There were 2,318 included visits; 197 developed septic shock (8.5%). Interventions Lasso with 10-fold cross-validation was used for variable selection; logistic regression was then used to construct a model from those variables in the training set. Variables were derived from electronic health record data known in the first 2 hours, including vital signs, medical history, demographics, and laboratory information. Test characteristics at two thresholds were evaluated: 1) optimizing sensitivity and specificity and 2) set to 90% sensitivity. Measurements and main results Septic shock was defined as systolic hypotension and vasoactive use or greater than or equal to 30 mL/kg isotonic crystalloid administration in the first 24 hours. A model was created using 20 predictors, with an area under the receiver operating curve in the training set of 0.85 (0.82-0.88); 0.83 (0.78-0.89) in the temporal test set and 0.83 (0.60-1.00) in the geographic test set. Sensitivity and specificity varied based on cutpoint; when sensitivity in the training set was set to 90% (83-94%), specificity was 62% (60-65%). Conclusions This model predicted risk of septic shock in children with suspected infection 2 hours after arrival, a critical timepoint for emergent treatment and transfer decisions. Varied cutpoints could be used to customize sensitivity to clinical context.

Background Fluid boluses aiming to improve the cardiac output and oxygen delivery are commonly administered in children with shock. An increased mean arterial pressure in addition to resolution of tachycardia and improved peripheral perfusion are often monitored as clinical surrogates for improvement in cardiac output. The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. Objective The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. Design, setting, patients, and interventions We prospectively analyzed hemodynamic data from children in the cardiac ICU who received fluid bolus (10mL/kg of Ringers-Lactate over 30 min) for management of shock and/or hypoperfusion within 12h of cardiac surgery. Cardiac index responders and mean arterial pressure-responders were defined as CI ≥10% and mean arterial pressure ≥10%, respectively. We evaluated the gradient for venous-return (mean systemic filling pressure-central venous pressure), arterial load properties (systemic vascular resistance index and elastance index) and changes in vasopressor support after fluid bolus. Measurements and main results Fifty-seven children between 1 month and 16 years (median Risk adjustment after congenital heart surgery Model for Outcome Surveillance in Australia and New Zealand score of 3.8 (interquartile range 3.7-4.6) received fluid bolus. Cardiac index-responsiveness and mean arterial pressure-responsiveness rates were 33% and 56%, respectively. No significant correlation was observed between changes in mean arterial pressure and cardiac index (r = 0.035, p = 0.79). Although the mean systemic filling pressure - central venous pressure and the number of cardiac index-responders after fluid bolus were similar, the arterial load parameters did not change in mean arterial pressure-nonresponders. Forty-three patients (75%) had a change in Vasoactive-Inotrope Score after the fluid bolus, of whom 60% received higher level of vasoactive support. Conclusions The mean arterial pressure response to fluid bolus in cardiac ICU patients was unpredictable with a poor relationship between cardiac index-responsiveness and mean arterial pressure-responsiveness. Because arterial hypotension is frequently a trigger for administering fluids and changes in blood pressure are commonly used for tracking changes in cardiac output, we suggest a cautious and individualized approach to repeat fluid bolus based solely on lack of mean arterial pressure response to the initial fluid, since the implications include decreased arterial tone even if the cardiac index increases.

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, β1, β2; 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.

Public health emergencies have the potential to place enormous strain on health systems. The current pandemic of the novel 2019 coronavirus disease has required hospitals in numerous countries to expand their surge capacity to meet the needs of patients with critical illness. When even surge capacity is exceeded, however, principles of critical care triage may be needed as a means to allocate scarce resources, such as mechanical ventilators or key medications. The goal of a triage system is to direct limited resources towards patients most likely to benefit from them. Implementing a triage system requires careful coordination between clinicians, health systems, local and regional governments, and the public, with a goal of transparency to maintain trust. We discuss the principles of tertiary triage and methods for implementing such a system, emphasizing that these systems should serve only as a last resort. Even under triage, we must uphold our obligation to care for all patients as best possible under difficult circumstances.

Objectives Pediatric protocols to guide allocation of limited resources during a disaster lack data to validate their use. The 2011 Pediatric Emergency Mass Critical Care Task Force recommended that expected duration of critical care be incorporated into resource allocation algorithms. We aimed to determine whether currently available pediatric illness severity scores can predict duration of critical care resource use. Design Retrospective cohort study. Setting Seattle Children's Hospital. Patients PICU patients admitted 2016-2018 for greater than or equal to 12 hours (n = 3,206). Interventions None. Measurements and main results We developed logistic and linear regression models in two-thirds of the cohort to predict need for and duration of PICU resources based on Pediatric Risk of Mortality-III, Pediatric Index of Mortality-3, and serial Pediatric Logistic Organ Dysfunction-2 scores. We tested the predictive accuracy of the models with the highest area under the receiver operating characteristic curve (need for each resource) and R (duration of use) in a validation cohort of the remaining one of three of the sample and among patients admitted during one-third of the sample and among patients admitted during surges of respiratory illness. Pediatric Logistic Organ Dysfunction score calculated 12 hours postadmission had higher predictive accuracy than either Pediatric Risk of Mortality or Pediatric Index of Mortality scores. Models incorporating 12-hour Pediatric Logistic Organ Dysfunction score, age, Pediatric Overall Performance Category, Pediatric Cerebral Performance Category, chronic mechanical ventilation, and postoperative status had an area under the receiver operating characteristic curve = 0.8831 for need for any PICU resource (positive predictive value 80.2%, negative predictive value 85.9%) and area under the receiver operating characteristic curve = 0.9157 for mechanical ventilation (positive predictive value 85.7%, negative predictive value 89.2%) within 7 days of admission. Models accurately predicted greater than or equal to 24 hours of any resource use for 78.9% of patients and greater than or equal to 24 hours of ventilation for 83.1%. Model fit and accuracy improved for prediction of resource use within 3 days of admission, and was lower for noninvasive positive pressure ventilation, vasoactive infusions, continuous renal replacement therapy, extracorporeal membrane oxygenation, and length of stay. Conclusions A model incorporating 12-hour Pediatric Logistic Organ Dysfunction score performed well in estimating how long patients may require PICU resources, especially mechanical ventilation. A pediatric disaster triage algorithm that includes both likelihood for survival and for requiring critical care resources could minimize subjectivity in resource allocation decision-making.

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.

Objectives To update the American Academy of Pediatrics and Society of Critical Care Medicine's 2004 Guidelines and levels of care for PICU. Design A task force was appointed by the American College of Critical Care Medicine to follow a standardized and systematic review of the literature using an evidence-based approach. The 2004 Admission, Discharge and Triage Guidelines served as the starting point, and searches in Medline (Ovid), Embase (Ovid), and PubMed resulted in 329 articles published from 2004 to 2016. Only 21 pediatric studies evaluating outcomes related to pediatric level of care, specialized PICU, patient volume, or personnel. Of these, 13 studies were large retrospective registry data analyses, six small single-center studies, and two multicenter survey analyses. Limited high-quality evidence was found, and therefore, a modified Delphi process was used. Liaisons from the American Academy of Pediatrics were included in the panel representing critical care, surgical, and hospital medicine expertise for the development of this practice guidance. The title was amended to "practice statement" and "guidance" because Grading of Recommendations, Assessment, Development, and Evaluation methodology was not possible in this administrative work and to align with requirements put forth by the American Academy of Pediatrics. Methods The panel consisted of two groups: a voting group and a writing group. The panel used an iterative collaborative approach to formulate statements on the basis of the literature review and common practice of the pediatric critical care bedside experts and administrators on the task force. Statements were then formulated and presented via an online anonymous voting tool to a voting group using a three-cycle interactive forecasting Delphi method. With each cycle of voting, statements were refined on the basis of votes received and on comments. Voting was conducted between the months of January 2017 and March 2017. The consensus was deemed achieved once 80% or higher scores from the voting group were recorded on any given statement or where there was consensus upon review of comments provided by voters. The Voting Panel was required to vote in all three forecasting events for the final evaluation of the data and inclusion in this work. The writing panel developed admission recommendations by level of care on the basis of voting results. Results The panel voted on 30 statements, five of which were multicomponent statements addressing characteristics specific to PICU level of care including team structure, technology, education and training, academic pursuits, and indications for transfer to tertiary or quaternary PICU. Of the remaining 25 statements, 17 reached consensus cutoff score. Following a review of the Delphi results and consensus, the recommendations were written. Conclusions This practice statement and level of care guidance manuscript addresses important specifications for each PICU level of care, including the team structure and resources, technology and equipment, education and training, quality metrics, admission and discharge criteria, and indications for transfer to a higher level of care. The sparse high-quality evidence led the panel to use a modified Delphi process to seek expert opinion to develop consensus-based recommendations where gaps in the evidence exist. Despite this limitation, the members of the Task Force believe that these recommendations will provide guidance to practitioners in making informed decisions regarding pediatric admission or transfer to the appropriate level of care to achieve best outcomes.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental appendices are available electronically (https://doi.org/10.1097/PCC.0000000000001735). The online documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

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.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.

Coronavirus disease 2019 has spread around the world. In the 3 months since its emergence, we have learned a great deal about its clinical management and its relevance to the pediatric critical care provider. In this article, we review the available literature and provide valuable insight into the clinical management of this disease, as well as information on preparedness activities that every PICU should perform.

In 2001, the Surviving Sepsis Campaign (SSC) began to develop evidence-based guidelines and recommendations for the resuscitation and management of patients with sepsis. With the 2016 edition, the Society of Critical Care Medicine and European Society of Intensive Care Medicine recommended a separate task force be dedicated to guideline formulation for children. The objective of the “Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children” is to provide guidance for the care of infants, children, and adolescents with septic shock and other sepsis-associated organ dysfunction. Recommendations are intended to guide “best practice” rather than to establish a treatment algorithm or to define standard of care and cannot replace the clinician's decision-making capability when presented with a patient's unique set of clinical variables.

Contains fulltext : 230013.pdf (Publisher’s version ) (Closed access) 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. 01 februari 2020

To deploy machine learning tools (random forests) to develop a model that reliably predicts hospital mortality in children with acute infections residing in low- and middle-income countries, using age and other variables collected at hospital admission.Post hoc analysis of a single-center, prospective, before-and-after feasibility trial.Rural district hospital in Rwanda, a low-income country in Sub-Sahara Africa.Infants and children greater than 28 days and less than 18 years of life hospitalized because of an acute infection.None.Age, vital signs (heart rate, respiratory rate, and temperature) capillary refill time, altered mental state collected at hospital admission, as well as survival status at hospital discharge were extracted from the trial database. This information was collected for 1,579 adult and pediatric patients admitted to a regional referral hospital with an acute infection in rural Rwanda. Nine-hundred forty-nine children were included in this analysis. We predicted survival in study subjects using random forests, a machine learning algorithm. Five prediction models, all including age plus two to five other variables, were tested. Three distinct optimization criteria of the algorithm were then compared. The in-hospital mortality was 1.5% (n = 14). All five models could predict in-hospital mortality with an area under the receiver operating characteristic curve ranging between 0.69 and 0.8. The model including age, respiratory rate, capillary refill time, altered mental state exhibited the highest predictive value area under the receiver operating characteristic curve 0.8 (95% CI, 0.78-0.8) with the lowest possible number of variables.A machine learning-based algorithm could reliably predict hospital mortality in a Sub-Sahara African population of 949 children with an acute infection using easily collected information at admission which includes age, respiratory rate, capillary refill time, and altered mental state. Future studies need to evaluate and strengthen this algorithm in larger pediatric populations, both in high- and low-/middle-income countries.

OBJECTIVE To evaluate whether a focused education program and implementation of a treatment bundle increases the rate of early evidence-based interventions in patients with acute infections. DESIGN Single-center, prospective, before-and-after feasibility trial. SETTING Emergency department of a sub-Saharan African district hospital. PATIENTS Patients > 28 days of life admitted to the study hospital for an acute infection. INTERVENTIONS The trial had three phases (each of four months). Interventions took place during the second (educational program followed by implementation of the treatment bundle) and third (provision of resources to implement treatment bundle) phases. MEASUREMENTS AND MAIN RESULTS Demographic, clinical, and laboratory data were collected at study enrollment; 24, 48, and 72 hours after hospital admission; and at discharge. A total of 1,594 patients were enrolled (pre-intervention, n = 661; intervention I, n = 531; intervention II, n = 402). The rate of early evidence-based interventions per patient during Intervention Phase I was greater than during the pre-intervention phase (74 ± 17 vs. 79 ± 15%, p < 0.001). No difference was detected when data were compared between Intervention Phases I and II (79 ± 15 vs. 80 ± 15%, p = 0.58). No differences in the incidence of blood transfusion (pre-intervention, 6%; intervention I, 7%; intervention II, 7%) or severe adverse events in the first 24 hours (allergic reactions: pre-intervention, 0.2%; intervention I, 0%; intervention II, 0%; respiratory failure: pre-intervention, 2%; intervention I, 2%; intervention II, 2%; acute renal failure: pre-intervention, 2%; intervention I, 2%; intervention II, 1%) were observed. CONCLUSIONS Our results indicate that a focused education program and implementation of an infection treatment bundle in clinical practice increased the rate of early evidence-based interventions in patients with acute infections (mostly malaria) admitted to a sub-Saharan African district hospital. Provision of material resources did not further increase this rate. While no safety issues were detected, this could be related to the very low disease severity of the enrolled patient population (www.clinicaltrials.gov: NCT02697513).

We evaluated adapting the quick Sequential (Sepsis-Related) Organ Failure Assessment score (fast respiratory rate, altered mental status, low blood pressure) for pediatric use by selecting thresholds from three commonly used definitions: Pediatric Logistic Organ Dysfunction 2, Pediatric Advanced Life Support, and International Pediatric Sepsis Consensus Conference. We examined their respective performance in identifying children who had a discharge diagnosis of infection at high risk of mortality using PICU registry data, with additional focus on the influence of age on performance.Analysis of retrospective data obtained from the Virtual Pediatric Systems PICU database. The performance in predicting observed mortality was assessed for the three candidate approaches using receiver operating characteristics analysis, including age group effects.The Virtual Pediatric Systems database contains data on diagnosis, clinical markers, and outcomes in prospectively collected clinical records from 130 participating PICUs in the United States and Canada.Children who had a discharge diagnosis of infection in a participating PICU between 2009 and 2014, for which all required data were available.None.Data from 40,228 children revealed an overall mortality of 4.22%. Area under the receiver operating characteristics curve (95% CI) was 0.760 (0.749-0.771) for Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation, 0.700 (0.689-0.712) for Pediatric Advanced Life Support, and 0.709 (0.696-0.721) for International Pediatric Sepsis Consensus Conference. When split by age group, the performance of Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation was lowest in the youngest neonates (under 1 wk old), with an area under the receiver operating characteristics curve (95% CI) of 0.724 (0.656-0.791), and in the teenagers (13-18 yr), with an area under the receiver operating characteristics curve of 0.710 (0.682-0.738), yet it still outperformed Pediatric Advanced Life Support and International Pediatric Sepsis Consensus Conference in both groups.Among critically ill children who had a discharge diagnosis of infection in the PICU, quick Sequential (Sepsis-Related) Organ Failure Assessment score performs best when using the Pediatric Logistic Organ Dysfunction 2 age thresholds with mechanical ventilation, while all definitions performed worse at extremes of pediatric age. Thus, mortality risk varies with vital sign thresholds, and although Pediatric Logistic Organ Dysfunction 2 with mechanical ventilation performed marginally better, it is unlikely to be of use to clinicians. More work is needed to develop a robust and relevant pediatric sepsis risk score.

Background The World Health Organization guidelines provide suggestions on early recognition and treatment of severe dengue (SD); however, mortality in this group can be high and is related both to disease severity and the treatment complications. Subjects and methods In this prospective observational study, we report our results where standard therapy (ST) was enhanced by Intensive Care Unit (ICU) supportive measures that have proven beneficial in other conditions that share similar pathophysiology of capillary leak and fluid overload. These include early albumin for crystalloid-refractory shock, proactive monitoring for symptomatic abdominal compartment syndrome (ACS), application of a high-risk intubation management protocol, and other therapies. We compared outcomes in a matched retrospective cohort who received ST. Results We found improved outcomes using these interventions in patients with the most devastating forms of dengue (ST+ group). We could demonstrate decreased positive fluid balance on days 1-3 and less symptomatic ACS that necessitated invasive percutaneous drainage (7.7% in ST+ group vs. 30% in ST group, P = 0.025). Other benefits in ST+ group included lower intubation and positive pressure ventilation requirements (18.4% in ST+ vs. 53.3% in ST, P = 0.003), lower incidence of major hemorrhage and acute kidney injury, and reduced pediatric ICU stays and mortality (2.6% in ST+ group vs. 26% in ST group, P = 0.004). Conclusion Children with SD with refractory shock are at extremely high mortality risk. We describe the proactive application of several targeted ICU supportive interventions in addition to ST and could show that these interventions resulted in decreased resuscitation morbidity and improved outcomes in SD.

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 Child

Children are affected by all types of disasters disproportionately compared with adults. Despite this, planning and readiness to care for children in disasters is suboptimal locally, nationally, and internationally. These planning gaps increase the likelihood that a disaster will have a greater negative impact on children when compared with adults. New voluntary regional coalitions have been developed to fill this gap. Some are pediatric focused or have pediatrics well integrated into the greater coalition. This article discusses key points of pediatric disaster planning, specific vulnerabilities, and the care of children in general and in specific disaster situations.

OBJECTIVE: Develop and test the performance of electronic versions of the Children’s Hospital of Pittsburgh pediatric risk of mortality (CHP e-PRISM-IV) and pediatric logistic organ dysfunction (CHP e-PELOD-2) scores. DESIGN: Retrospective, single-center cohort derived from structured electronic health record data. SETTING: Large, quaternary pediatric intensive care unit (PICU) at a freestanding, university-affiliated children’s hospital. PATIENTS: All encounters with a PICU admission between January 1, 2009 and December 31, 2017 identified using electronic definitions of inpatient encounter. MEASUREMENTS: The main outcome was predictive validity of each score for hospital mortality, assessed as model discrimination and calibration. Discrimination was examined with the area under the receiver operating characteristics curve (AUROC) and the area under the precision-recall curve (AUPRC). Calibration was assessed with the Hosmer-Lemeshow goodness of fit test and calculation of a standardized mortality ratio (SMR). Models were recalibrated with new regression coefficients in a training subset of 75% of encounters selected randomly from all years of the cohort and the calibrated models were tested in the remaining 25% of the cohort. Content validity was assessed by examining correlation between electronic versions of the scores and prospectively calculated data (CHP e-PRISM-IV) and an alternative informatics approach (CHP e-PELOD-2). RESULTS: The cohort included 21,335 encounters. Correlation coefficients indicated strong agreement between different methods of score calculation. Uncalibrated AUROCs were 0.96 (95% confidence interval 0.95-0.97) for CHP e-PELOD-2 and 0.87 (0.85-0.89) for e-CHP PRISM-IV for inpatient mortality. The uncalibrated CHP e-PRISM-IV SMR was 0.63 (0.59-0.66), demonstrating strong agreement with previous, prospective evaluation at the study center. The uncalibrated CHP e-PELOD-2 SMR was 0.20 (0.18-0.21). All models required recalibrating (all Hosmer-Lemeshow goodness of fit P

To produce a treatment algorithm for the ICU management of infants, children, and adolescents with severe traumatic brain injury.Studies included in the 2019 Guidelines for the Management of Pediatric Severe Traumatic Brain Injury (Glasgow Coma Scale score ≤ 8), consensus when evidence was insufficient to formulate a fully evidence-based approach, and selected protocols from included studies.Baseline care germane to all pediatric patients with severe traumatic brain injury along with two tiers of therapy were formulated. An approach to emergent management of the crisis scenario of cerebral herniation was also included. The first tier of therapy focuses on three therapeutic targets, namely preventing and/or treating intracranial hypertension, optimizing cerebral perfusion pressure, and optimizing partial pressure of brain tissue oxygen (when monitored). The second tier of therapy focuses on decompressive craniectomy surgery, barbiturate infusion, late application of hypothermia, induced hyperventilation, and hyperosmolar therapies.This article provides an algorithm of clinical practice for the bedside practitioner based on the available evidence, treatment protocols described in the articles included in the 2019 guidelines, and consensus that reflects a logical approach to mitigate intracranial hypertension, optimize cerebral perfusion, and improve outcomes in the setting of pediatric severe traumatic brain injury.

Sepsis is a major reason for intensive care unit (ICU) admission, also in resource–poor settings. ICUs in low– and middle–income countries (LMICs) face many challenges that could affect patient outcome. The aim of this review is to describe differences between resource–poor and resource–rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Although many bacterial pathogens causing sepsis in LMICs are similar to those in high–income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Addressing both disease–specific and setting–specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost–effective in LMIC setting, more detailed evaluation at both at a macro– and micro–economy level is necessary. Sepsis management in resource–limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

BACKGROUND Sepsis, worldwide the leading cause of death in children, has now been recognized as the global health emergency it is. On May 26, 2017, the World Health Assembly, the decision-making body of the World Health Organization, adopted a resolution proposed by the Global Sepsis Alliance to improve the prevention, diagnosis, and management of sepsis. OBJECTIVE To discuss the implications of this resolution for children worldwide. CONCLUSIONS The resolution highlights sepsis as a global threat and urges the 194 United Nations member states to take specific actions and implement appropriate measures to reduce its human and health economic burden. The resolution is a major step toward achieving the targets outlined by the Sustainable Developmental Goals for decreasing mortality in infants and children, but implementing it will require a concerted global effort.

To review important articles in the field of pediatric shock and pediatric septic shock published subsequent to the Fifth Edition of the Rogers' Textbook of Pediatric Intensive Care.The U.S. National Library of Medicine PubMed (www.ncbi.nlm.nih.gov/pubmed) was searched for combination of the term "pediatric" and the following terms: "sepsis, septic shock, shock, antibiotics, extracorporeal membrane oxygenation, and steroid." The abstract lists generated by these searches were screened for potential inclusion. The authors were also aware of a number of key recent articles in pediatric shock, and these were also screened.Promising articles published subsequent to the fifth edition of the textbook were included based on the consensus of the authors and via the peer review process.Articles were grouped by category. Each author was assigned categories and extracted data from articles in that category. All authors contributed to final review of extracted data.Articles in the following categories were included: epidemiology and recognition of shock; laboratory markers of shock; antimicrobial therapy; vasoactive therapy; extracorporeal therapies; mortality patterns, prediction, and risk stratification; bundled approaches to shock recognition and management; and corticosteroid use.Research efforts in pediatric shock have largely centered on pediatric septic shock, with significant progress in the understanding of sepsis epidemiology, the use of extracorporeal therapies in critically ill children with sepsis, the role of hyperlactatemia and risk stratification in pediatric septic shock, and the impact of bundled care for pediatric sepsis, including evaluation of individual bundle elements such as the optimal timing of antibiotic administration and vasoactive medication choice. A consistent theme in the literature is the beneficial role of a bundled approach to septic shock recognition and management to improve both care and outcomes.

Acute infectious diseases are the most common cause of under-5 mortality. However, the hospital burden of nonneonatal pediatric sepsis has not previously been described in the resource poor setting. The objective of this study was to determine the prevalence of sepsis among children 6 months to 5 years old admitted with proven or suspected infection and to evaluate the presence of sepsis as a predictive tool for mortality during admission.In this prospective cohort study, we used the pediatric International Consensus Conference definition of sepsis to determine the prevalence of sepsis among children admitted to the pediatric ward with a proven or suspected infection. The diagnosis of sepsis, as well as each individual component of the sepsis definition, was evaluated for capturing in-hospital mortality.The pediatric ward of two hospitals in Mbarara, Uganda.Admitted children between 6 months and 5 years with a confirmed or suspected infection.None.One thousand three hundred seven (1,307) subjects with a confirmed or suspected infection were enrolled, and 65 children died (5.0%) during their admission. One thousand one hundred twenty-one (85.9%) met the systemic inflammatory response syndrome criteria, and therefore, they were defined as having sepsis. The sepsis criteria captured 61 deaths, demonstrating a sensitivity and a specificity of 95% (95% CI, 90-100%) and 15% (95% CI, 13-17%), respectively. The most discriminatory individual component of the systemic inflammatory response syndrome criteria was the leukocyte count, which alone had a sensitivity of 72% and a specificity of 56% for the identification of mortality in hospital.This study is among the first to quantify the burden of nonneonatal pediatric sepsis in children with suspected infection, using the international consensus sepsis definition, in a typical resource-constrained setting in Africa. This definition was found to be highly sensitive in identifying those who died but had very low specificity as most children who were admitted with infections had sepsis. The systemic inflammatory response syndrome-based sepsis definition offers little value in identification of children at high risk of in-hospital mortality in this setting.

Aims: We previously reported that vasodilatation was common in pediatric septic shock, regardless of whether they were warm or cold, providing a rationale for early norepinephrine (NE) to increase venous return (VR) and arterial tone. Our primary aim was to evaluate the effect of smaller fluid bolus plus early-NE versus the American College of Critical Care Medicine (ACCM) approach to more liberal fluid boluses and vasoactive-inotropic agents on fluid balance, shock resolution, ventilator support and mortality in children with septic shock. Secondly, the impact of early NE on hemodynamic parameters, urine output and lactate levels was assessed using multimodality-monitoring. Methods: In keeping with the primary aim, the early NE group (N-27) received NE after 30ml/kg fluid, while the ACCM group (N-41) were a historical cohort managed as per the ACCM Guidelines, where after 40-60ml/kg fluid, patients received first line vasoactive-inotropic agents. The effect of early-NE was characterized by measuring stroke volume variation(SVV), systemic vascular resistance index (SVRI) and cardiac function before and after NE, which were monitored using ECHO + Ultrasound-Cardiac-Output-Monitor (USCOM) and lactates. Results: The 6-hr fluid requirement in the early-NE group (88.9+31.3 to 37.4+15.1ml/kg), and ventilated days [median 4 days (IQR 2.5-5.25) to 1day (IQR 1-1.7)] were significantly less as compared to the ACCM group. However, shock resolution and mortality rates were similar. In the early NE group, the overall SVRI was low (mean 679.7dynes/sec/cm5/m2, SD 204.5), and SVV decreased from 23.8±8.2 to 18.5±9.7, p=0.005 with NE infusion suggesting improved preload even without further fluid loading. Furthermore, lactate levels decreased and urine-output improved. Conclusion: Early-NE and fluid restriction may be of benefit in resolving shock with less fluid and ventilator support as compared to the ACCM approach.