Early bolus epinephrine administration during pediatric cardiopulmonary resuscitation for bradycardia with poor perfusion: an ICU-resuscitation study.

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.

Comparing AVPU and Glasgow Coma Scales Among Children Seen by Emergency Medical Services.

OBJECTIVES: Consciousness assessment is an important component in the prehospital care of ill or injured children. Both the Glasgow Coma Scale (GCS) and the Alert, Verbal, Pain, Unresponsive (AVPU) scale are used for this purpose. We sought to identify cut points for the GCS to correspond to the AVPU scale for pediatric emergency medical services (EMS) encounters. METHODS: We conducted a retrospective cross-sectional analysis using the 2019-2022 National EMS Information System data set, including children (<18 years) with a GCS and AVPU score. We evaluated several approaches to develop cut points for the GCS within the AVPU scale and reported measures of performance. RESULTS: Of 6 186 663 pediatric encounters, 4 311 598 with both GCS and AVPU documentation were included (median age was 10 years [interquartile range 3-15]; 50.9% boys). Lower AVPU scores correlated with life-sustaining procedures, including those for airway management, seizure, and cardiac arrest. Optimal GCS cut points obtained via a grid-based search were 14 to 15 for alert, 11 to 13 for verbal, 7 to 10 for pain, and 3 to 6 for unresponsive. Overall accuracy was 0.95, with kappa of 0.61. Intraclass F1 statistics were lower for verbal (0.37) and pain (0.50) categories compared with alert (0.98) and unresponsive (0.78). CONCLUSIONS: We developed a cross-walking between the AVPU and GCS scales. Overall performance was high, though performance within the verbal and pain categories was lower. These findings can be useful to enhance clinician handovers and to aid in the development of EMS-based prediction models.

A randomized, embedded, pragmatic, Bayesian clinical trial examining clinical decision support for high flow nasal cannula management in children with bronchiolitis: design and statistical analysis plan.

BACKGROUND: High flow nasal cannula (HFNC) has been increasingly adopted in the past 2 decades as a mode of respiratory support for children hospitalized with bronchiolitis. The growing use of HFNC despite a paucity of high-quality data regarding the therapy's efficacy has led to concerns about overutilization. We developed an electronic health record (EHR) embedded, quality improvement (QI) oriented clinical trial to determine whether standardized management of HFNC weaning guided by clinical decision support (CDS) results in a reduction in the duration of HFNC compared to usual care for children with bronchiolitis. METHODS: The design and summary of the statistical analysis plan for the REspiratory SupporT for Efficient and cost-Effective Care (REST EEC; "rest easy") trial are presented. The investigators hypothesize that CDS-coupled, standardized HFNC weaning will reduce the duration of HFNC, the trial's primary endpoint, for children with bronchiolitis compared to usual care. Data supporting trial design and eventual analyses are collected from the EHR and other real world data sources using existing informatics infrastructure and QI data sources. The trial workflow, including randomization and deployment of the intervention, is embedded within the EHR of a large children's hospital using existing vendor features. Trial simulations indicate that by assuming a true hazard ratio effect size of 1.27, equivalent to a 6-h reduction in the median duration of HFNC, and enrolling a maximum of 350 children, there will be a > 0.75 probability of declaring superiority (interim analysis posterior probability of intervention effect > 0.99 or final analysis posterior probability of intervention effect > 0.9) and a > 0.85 probability of declaring superiority or the CDS intervention showing promise (final analysis posterior probability of intervention effect > 0.8). Iterative plan-do-study-act cycles are used to monitor the trial and provide targeted education to the workforce. DISCUSSION: Through incorporation of the trial into usual care workflows, relying on QI tools and resources to support trial conduct, and relying on Bayesian inference to determine whether the intervention is superior to usual care, REST EEC is a learning health system intervention that blends health system operations with active evidence generation to optimize the use of HFNC and associated patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05909566. Registered on June 18, 2023.

Automatic Population of the Case Report Forms for an International Multifactorial Adaptive Platform Trial Amid the COVID-19 Pandemic.

OBJECTIVES: To automatically populate the case report forms (CRFs) for an international, pragmatic, multifactorial, response-adaptive, Bayesian COVID-19 platform trial. METHODS: The locations of focus included 27 hospitals and 2 large electronic health record (EHR) instances (1 Cerner Millennium and 1 Epic) that are part of the same health system in the United States. This paper describes our efforts to use EHR data to automatically populate four of the trial's forms: baseline, daily, discharge, and response-adaptive randomization. RESULTS: Between April 2020 and May 2022, 417 patients from the UPMC health system were enrolled in the trial. A MySQL-based extract, transform, and load pipeline automatically populated 499 of 526 CRF variables. The populated forms were statistically and manually reviewed and then reported to the trial's international data coordinating center. CONCLUSIONS: We accomplished automatic population of CRFs in a large platform trial and made recommendations for improving this process for future trials.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

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

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

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit.

Importance: Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. Objective: To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. Design, Setting, and Participants: This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). Main Outcomes and Measures: The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Results: Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Conclusions and Relevance: Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.

Centiles for the shock index among injured children in the prehospital setting.

OBJECTIVE: The shock index (SI), the ratio of heart rate to systolic blood pressure, is a clinical tool for assessing injury severity. Age-adjusted SI models may improve predictive value for injured children in the out-of-hospital setting. We sought to characterize the proportion of children in the prehospital setting with an abnormal SI using established criteria, describe the age-based distribution of SI among injured children, and determine prehospital interventions by SI. METHODS: We performed a multi-agency retrospective cross-sectional study of children (<18 years) in the prehospital setting with a scene encounter for suspected trauma and transported to the hospital between 2018 and 2022 using the National Emergency Medical Services (EMS) Information System datasets. Our exposure of interest was the first calculated SI. We identified the proportion of children with an abnormal SI when using the SI, pediatric age-adjusted (SIPA); and the pediatric SI (PSI) criteria. We developed and internally validated an age-based distributional model for the SI using generalized additive models for location, scale, and shape to describe the age-based distribution of the SI as a centile or Z-score. We evaluated EMS interventions (basic airway interventions, advanced airway interventions, cardiac interventions, vascular access, intravenous fluids, and vasopressor use) in relation to both the SIPA, PSI, and distributional SI values. RESULTS: We analyzed 1,007,863 pediatric EMS trauma encounters (55.0% male, median age 13 years [IQR, 8-16 years]). The most common dispatch complaint was for traffic/transport related injury (32.9%). When using the PSI and SIPA, 13.1% and 16.3% were classified as having an abnormal SI, respectively. There were broad differences in the percentage of encounters classified as having an abnormal SI across the age range, varying from 5.1 to 22.8% for SIPA and 3.7-20.1% for PSI. The SIPA values ranged from the 75th to 95th centiles, while the PSI corresponded to an SI greater than the 90th centile, except in older children. The centile distribution for SI declined during early childhood and stabilized during adolescence and demonstrated a difference of <0.1% at cutoff values. An abnormal PSI, SIPA and higher SI centiles (>90th centile and >95th centiles) were associated with interventions related to basic and advanced airway management, cardiac procedures, vascular access, and provision of intravenous fluids occurred with greater frequency at higher SI centiles. Some procedures, including airway management and vascular access, had a smaller peak at lower (<10th) centiles. DISCUSSION: We describe the empiric distribution of the pediatric SI across the age range, which may overcome limitations of extant criteria in identifying patients with shock in the prehospital setting. Both high and low SI values were associated with important, potentially lifesaving EMS interventions. Future work may allow for more precise identification of children with significant injury using cutpoint analysis paired to outcome-based criteria. These may additionally be combined with other physiologic and mechanistic criteria to assist in triage decisions.

Association of Pediatric Postcardiac Arrest Ventilation and Oxygenation with Survival Outcomes.

Rationale: Adult and pediatric studies provide conflicting data regarding whether post-cardiac arrest hypoxemia, hyperoxemia, hypercapnia, and/or hypocapnia are associated with worse outcomes. Objectives: We sought to determine whether postarrest hypoxemia or postarrest hyperoxemia is associated with lower rates of survival to hospital discharge, compared with postarrest normoxemia, and whether postarrest hypocapnia or hypercapnia is associated with lower rates of survival, compared with postarrest normocapnia. Methods: An embedded prospective observational study during a multicenter interventional cardiopulmonary resuscitation trial was conducted from 2016 to 2021. Patients ⩽18 years old and with a corrected gestational age of ≥37 weeks who received chest compressions for cardiac arrest in one of the 18 intensive care units were included. Exposures during the first 24 hours postarrest were hypoxemia, hyperoxemia, or normoxemia-defined as lowest arterial oxygen tension/pressure (PaO2) <60 mm Hg, highest PaO2 ⩾200 mm Hg, or every PaO2 60-199 mm Hg, respectively-and hypocapnia, hypercapnia, or normocapnia, defined as lowest arterial carbon dioxide tension/pressure (PaCO2) <30 mm Hg, highest PaCO2 ⩾50 mm Hg, or every PaCO2 30-49 mm Hg, respectively. Associations of oxygenation and carbon dioxide group with survival to hospital discharge were assessed using Poisson regression with robust error estimates. Results: The hypoxemia group was less likely to survive to hospital discharge, compared with the normoxemia group (adjusted relative risk [aRR] = 0.71; 95% confidence interval [CI] = 0.58-0.87), whereas survival in the hyperoxemia group did not differ from that in the normoxemia group (aRR = 1.0; 95% CI = 0.87-1.15). The hypercapnia group was less likely to survive to hospital discharge, compared with the normocapnia group (aRR = 0.74; 95% CI = 0.64-0.84), whereas survival in the hypocapnia group did not differ from that in the normocapnia group (aRR = 0.91; 95% CI = 0.74-1.12). Conclusions: Postarrest hypoxemia and hypercapnia were each associated with lower rates of survival to hospital discharge.

Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

OBJECTIVES: Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. DESIGN: Retrospective, electronic medical record linkage, cohort study. SETTING: Quaternary PICU. PATIENTS: Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). MEASUREMENTS AND MAIN RESULTS: ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. CONCLUSIONS: A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

Child Health Needs and the Pediatric Critical Care Medicine Workforce: 2020-2040.

This article, focused on the current and future pediatric critical care medicine (PCCM) workforce, is part of a supplement in Pediatrics anticipating the future supply of the pediatric subspecialty workforce. It draws on information available in the literature, data from the American Board of Pediatrics, and findings from a model that estimates the future supply of pediatric subspecialists developed by the American Board of Pediatrics Foundation in collaboration with the Carolina Workforce Research Center at the University of North Carolina at Chapel Hill's Cecil G. Sheps Center for Health Services Research and Strategic Modeling and Analysis Ltd. A brief history of the field of PCCM is provided, followed by an in-depth examination of the current PCCM workforce and a subsequent evaluation of workforce forecasts from 2020 to 2040. Under baseline conditions, the PCCM workforce is expected to increase by 105% during the forecasted period, more than any other pediatric subspecialty. Forecasts are modeled under a variety of multifactorial conditions meant to simulate the effects of changes to the supply of PCCM subspecialists, with only modest changes observed. Future PCCM workforce demand is unclear, although some suggest an oversupply may exist and that market forces may correct this. The findings generate important questions regarding the future state of the PCCM workforce and should be used to guide trainees considering a PCCM career, subspecialty leaders responsible for hosting training programs, staffing ICUs, and governing bodies that oversee training program accreditation and subspecialist certification.

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.

Survival With Favorable Neurologic Outcome and Quality of Cardiopulmonary Resuscitation Following In-Hospital Cardiac Arrest in Children With Cardiac Disease Compared With Noncardiac Disease.

OBJECTIVES: To assess associations between outcome and cardiopulmonary resuscitation (CPR) quality for in-hospital cardiac arrest (IHCA) in children with medical cardiac, surgical cardiac, or noncardiac disease. DESIGN: Secondary analysis of a multicenter cluster randomized trial, the ICU-RESUScitation Project (NCT02837497, 2016-2021). SETTING: Eighteen PICUs. PATIENTS: Children less than or equal to 18 years old and greater than or equal to 37 weeks postconceptual age receiving chest compressions (CC) of any duration during the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,100 children with IHCA, there were 273 medical cardiac (25%), 383 surgical cardiac (35%), and 444 noncardiac (40%) cases. Favorable neurologic outcome was defined as no more than moderate disability or no worsening from baseline Pediatric Cerebral Performance Category at discharge. The medical cardiac group had lower odds of survival with favorable neurologic outcomes compared with the noncardiac group (48% vs 55%; adjusted odds ratio [aOR] [95% CI], aOR 0.59 [95% CI, 0.39-0.87], p = 0.008) and surgical cardiac group (48% vs 58%; aOR 0.64 [95% CI, 0.45-0.9], p = 0.01). We failed to identify a difference in favorable outcomes between surgical cardiac and noncardiac groups. We also failed to identify differences in CC rate, CC fraction, ventilation rate, intra-arrest average target diastolic or systolic blood pressure between medical cardiac versus noncardiac, and surgical cardiac versus noncardiac groups. The surgical cardiac group had lower odds of achieving target CC depth compared to the noncardiac group (OR 0.15 [95% CI, 0.02-0.52], p = 0.001). We failed to identify a difference in the percentage of patients achieving target CC depth when comparing medical cardiac versus noncardiac groups. CONCLUSIONS: In pediatric IHCA, medical cardiac patients had lower odds of survival with favorable neurologic outcomes compared with noncardiac and surgical cardiac patients. We failed to find differences in CPR quality between medical cardiac and noncardiac patients, but there were lower odds of achieving target CC depth in surgical cardiac compared to noncardiac patients.

New Functional Impairment After Hospital Discharge by Traumatic Brain Injury Mechanism in Younger Than 3 Years Old Admitted to the PICU in a Single Center Retrospective Study.

OBJECTIVES: Children who suffer traumatic brain injury (TBI) are at high risk of morbidity and mortality. We hypothesized that in patients with TBI, the abusive head trauma (AHT) mechanism vs. accidental TBI (aTBI) would be associated with higher frequency of new functional impairment between baseline and later follow-up. DESIGN: Retrospective single center cohort study. SETTING AND PATIENTS: Children younger than 3 years old admitted with TBI to the PICU at a level 1 trauma center between 2014 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, TBI mechanism, and Functional Status Scale (FSS) scores at baseline, hospital discharge, short-term (median, 10 mo [interquartile range 3-12 mo]), and long-term (median, 4 yr [3-6 yr]) postdischarge were abstracted from the electronic health record. New impairment was defined as an increase in FSS greater than 1 from baseline. Patients who died were assigned the highest score (30). Multivariable logistic regression was performed to determine the association between TBI mechanism with new impairment. Over 6 years, there were 460 TBI children (170 AHT, 290 aTBI), of which 13 with AHT and four with aTBI died. Frequency of new impairment by follow-up interval, in AHT vs. aTBI patients, were as follows: hospital discharge (42/157 [27%] vs. 27/286 [9%]; p < 0.001), short-term (42/153 [27%] vs. 26/259 [10%]; p < 0.001), and long-term (32/114 [28%] vs. 18/178 [10%]; p < 0.001). Sensory, communication, and motor domains were worse in AHT patients at the short- and long-term timepoint. On multivariable analysis, AHT mechanism was associated with greater odds (odds ratio [95% CI]) of poor outcome (death and new impairment) at hospital discharge (4.4 [2.2-8.9]), short-term (2.7 [1.5-4.9]), and long-term timepoints (2.4 [1.2-4.8]; p < 0.05). CONCLUSIONS: In patients younger than 3 years old admitted to the PICU after TBI, the AHT mechanism-vs. aTBI-is associated with greater odds of poor outcome in the follow-up period through to ~5 years postdischarge. New impairment occurred in multiple domains and only AHT patients further declined in FSS over time.

Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

OBJECTIVES: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. DESIGN: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). SETTING: Eighteen ICUs participated in ICU-RESUS. PATIENTS: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation. CONCLUSIONS: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome.

EMERGENCE OF A TECHNOLOGY-DEPENDENT PHENOTYPE OF PEDIATRIC SEPSIS IN A LARGE CHILDREN'S HOSPITAL.

ABSTRACT: Objective: To investigate whether pediatric sepsis phenotypes are stable in time. Methods: Retrospective cohort study examining children with suspected sepsis admitted to a Pediatric Intensive Care Unit at a large freestanding children's hospital during two distinct periods: 2010-2014 (early cohort) and 2018-2020 (late cohort). K-means consensus clustering was used to derive types separately in the cohorts. Variables included ensured representation of all organ systems. Results: One thousand ninety-one subjects were in the early cohort and 737 subjects in the late cohort. Clustering analysis yielded four phenotypes in the early cohort and five in the late cohort. Four types were in both: type A (34% of early cohort, 25% of late cohort), mild sepsis, with minimal organ dysfunction and low mortality; type B (25%, 22%), primary respiratory failure; type C (25%, 18%), liver dysfunction, coagulopathy, and higher measures of systemic inflammation; type D (16%, 17%), severe multiorgan dysfunction, with high degrees of cardiorespiratory support, renal dysfunction, and highest mortality. Type E was only detected in the late cohort (19%) and was notable for respiratory failure less severe than B or D, mild hypothermia, and high proportion of diagnoses and technological dependence associated with medical complexity. Despite low mortality, this type had the longest PICU length of stay. Conclusions: This single center study identified four pediatric sepsis phenotypes in an earlier epoch but five in a later epoch, with the new type having a large proportion of characteristics associated with medical complexity, particularly technology dependence. Personalized sepsis therapies need to account for this expanding patient population.

Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.