Patient sex and outcomes in children with life-threatening hemorrhage.

BACKGROUND: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies. STUDY DESIGN AND METHODS: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses. RESULTS: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. CONCLUSION: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age.

Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.

Cryoprecipitate for the treatment of life-threatening hemorrhage in children.

BACKGROUND: Hypofibrinogenemia is an important risk factor for poor outcomes in children with severe bleeding. There is a paucity of data on the impact of cryoprecipitate transfusion on outcomes in pediatric patients with life-threatening hemorrhage (LTH). STUDY DESIGN AND METHODS: This secondary analysis of a multicenter prospective observational study of children with LTH investigated subjects who were categorized by receipt of cryoprecipitate during their resuscitation and according to the etiology of their bleeding: trauma, operative, and medical. Bivariate analysis was performed to identify variables associated with 6-h, 24-h, and 28-day mortality. Cox Hazard regression models were generated to adjust for potential confounders. RESULTS: Cryoprecipitate was transfused to 33.9% (152/449) of children during LTH. The median (Interquartile range) time to cryoprecipitate administration was 108 (47-212) minutes. Children in the cryoprecipitate group were younger, more often female, with higher BMI and pre-LTH PRISM score and lower platelet counts. After adjusting for PRISM score, bleeding etiology, age, sex, RBC volume, platelet volume, antifibrinolytic use and cardiac arrest, cryoprecipitate administration was independently associated with lower 6-h mortality, Hazard Ratio (95% CI), 0.41 (0.19-0.89), (p = 0.02) and 24-h mortality, Hazard Ratio (95% CI), 0.46 (0.24-0.89), (p = 0.02). CONCLUSION: Cryoprecipitate transfusion to children with LTH was associated with reduced early mortality. A prospective randomized trial is needed to determine if cryoprecipitate can improve outcomes in children with LTH.

Epsilon aminocaproic acid is associated with acute kidney injury after life-threatening hemorrhage in children.

BACKGROUND: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). STUDY DESIGN AND METHODS: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life-threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. RESULTS: Of 448 children included, median (interquartile range) age was 7 (2-15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety-three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty-seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre-LTH, and total weight-adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0-10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. CONCLUSION: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients.

Parent perceptions of emergent blood transfusion in children.

BACKGROUND: RhD-negative blood products are in chronic short supply leading to renewed interest in utilizing RhD-positive blood products for emergency transfusions. This study assessed parental perceptions of emergency RhD-positive blood use in children. METHODS: A survey of parents/guardians was conducted on their tolerance of transfusing RhD-positive blood to RhD-negative female children ≤17 years old at four level 1 pediatric hospitals. RESULTS: In total, 621 parents/guardians were approached of whom 378/621 (61%) completed the survey in its entirety and were included in the analysis. Respondents were mostly females [295/378 (78%)], White [242/378 (64%)], had some college education [217/378 (57%)] and less than $60,000 annual income [193/378 (51%)]. Respondents had a total of 547 female children. Most children's ABO [320/547 (59%)] and RhD type [348/547 (64%)] were not known by their parents; of children with known RhD type, 58/186 (31%) were RhD-negative. When the risk of harm to a future fetus was given as 0-6%, more than 80% of respondents indicated that they were likely to accept RhD-positive blood transfusions on behalf of RhD-negative female children in a life-threatening situation. The rate of willingness to accept emergent RhD-incompatible blood transfusions significantly increased as the potential survival benefit of the transfusion increased. CONCLUSION: Most parents were willing to accept RhD-positive blood products on behalf of RhD-negative female children in an emergency situation. Further discussions and evidence-based guidelines on transfusing RhD-positive blood products to RhD-unknown females in emergency settings are needed.

Blood component ratios in children with non-traumatic life-threatening bleeding.

BACKGROUND AND OBJECTIVES: In paediatric trauma patients, there are limited prospective data regarding blood components and mortality, with some literature suggesting decreased mortality with high ratios of plasma and platelets to red blood cells (RBCs) in massive transfusions; however, most paediatric massive transfusions occur for non-traumatic aetiologies and few studies assess blood product ratios in these children. This study's objective was to evaluate whether high blood product ratios or low deficits conferred a survival benefit in children with non-traumatic life-threatening bleeding. MATERIALS AND METHODS: This is a secondary analysis of the five-year, multicentre, prospective, observational massive transfusion epidemiology and outcomes in children study of children with life-threatening bleeding from US, Canadian and Italian medical centres. Primary interventions were plasma:RBC and platelets:RBC (high ratio ≥1:2 ml/kg) and plasma and platelet deficits. The primary outcome was mortality at 6 h, 24 h and 28 days. Multivariate logistic regression models were used to determine independent associations with mortality. RESULTS: A total of 222 children were included from 24 medical centres: 145 children (median [interquartile range] age 2.1 years [0.3-11.8]) with operative bleeding and 77 (8.0 years [1.2-14.7]) with medical bleeding. In adjusted analyses, neither blood product ratios nor deficits were associated with mortality at 6 h, 24 h or 28 days. CONCLUSION: This paper addresses a lack of prospective data in children regarding optimal empiric massive transfusion strategies in non-traumatic massive haemorrhage and in finding no decrease in mortality with high plasma or platelet to RBC ratios or lower deficits supports an exploratory analysis for mortality.

Doubly structured sparsity for grouped multivariate responses with application to functional outcome score modeling.

This work is motivated by the need to accurately model a vector of responses related to pediatric functional status using administrative health data from inpatient rehabilitation visits. The components of the responses have known and structured interrelationships. To make use of these relationships in modeling, we develop a two-pronged regularization approach to borrow information across the responses. The first component of our approach encourages joint selection of the effects of each variable across possibly overlapping groups of related responses and the second component encourages shrinkage of effects towards each other for related responses. As the responses in our motivating study are not normally-distributed, our approach does not rely on an assumption of multivariate normality of the responses. We show that with an adaptive version of our penalty, our approach results in the same asymptotic distribution of estimates as if we had known in advance which variables have non-zero effects and which variables have the same effects across some outcomes. We demonstrate the performance of our method in extensive numerical studies and in an application in the prediction of functional status of pediatric patients using administrative health data in a population of children with neurological injury or illness at a large children's hospital.

Cost analysis of hospitals performing continuous albuterol in non-intensive care settings.

OBJECTIVE: To compare hospital costs and resource utilization for pediatric asthma admissions based on the hospitals' availability of continuous albuterol aerosolization administration (CAA) in non-intensive care unit (ICU) settings. METHODS: We conducted a retrospective cohort study of children ages 2-17 years admitted in 2019 with a principal diagnosis of asthma using the Pediatric Health Information System. Hospitals and hospitalizations were categorized based on location of CAA administration, ICU-only versus general inpatient floors. Hospitals preforming CAA in an intermediate care unit were excluded. We calculated total cost, standardized unit costs and rates of interventions. Groups were compared using Chi-Square, t-test and Wilcoxon rank-sum test as indicated. A log linear mixed model was created to evaluate potential confounders. RESULTS: Twenty-one hospitals (7084 hospitalizations) allowed CAA on the floor.Twenty-four hospitals (6100 hospitalizations) allowed CAA in the ICU-only. Median total cost was $4639 (Interquartile Range (IQR) $3060-$7512) for the floor group and $5478 (IQR $3444-$8539) for the ICU-only group (p < 0.001) (mean cost difference of $775 per patient). Hospitalization costs were $4,726,829 (95% CI $3,459,920-$5,993,860) greater for the children treated at hospitals restricting CAA to the ICU. We observed higher standardized laboratory, imaging, clinical and other unit costs, along with higher use of interventions in the ICU-only group. After adjustment, we found that ICU stay and hospital LOS were the main drivers of cost difference between the groups. CONCLUSIONS: There was cost savings and decreased resource utilization for hospitals that performed CAA on the floor. Further studies exploring variations in asthma management are warranted.

Using Billing Codes to Create a Pediatric Functional Status e-Score for Children Receiving Inpatient Rehabilitation.

OBJECTIVE: Provide proof-of-concept for development of a Pediatric Functional Status eScore (PFSeS). Demonstrate that expert clinicians rank billing codes as relevant to patient functional status and identify the domains that codes inform in a way that reliably matches analytical modeling. DESIGN: Retrospective chart review, modified Delphi, and nominal group techniques. SETTING: Large, urban, quaternary care children's hospital in the Midwestern United States. PARTICIPANTS: Data from 1955 unique patients and 2029 hospital admissions (2000-2020); 12 expert consultants representing the continuum of rehabilitation care reviewed 2893 codes (procedural, diagnostic, pharmaceutical, durable medical equipment). MAIN OUTCOME MEASURES: Consensus voting to determine whether codes were associated with functional status at discharge and, if so, what domains they informed (self-care, mobility, cognition/ communication). RESULTS: The top 250 and 500 codes identified by statistical modeling were mostly composed of codes selected by the consultant panel (78%-80% of the top 250 and 71%-78% of the top 500). The results provide evidence that clinical experts' selection of functionally meaningful codes corresponds with codes selected by statistical modeling as most strongly associated with WeeFIM domain scores. The top 5 codes most strongly related to functional independence ratings from a domain-specific assessment indicate clinically sensible relationships, further supporting the use of billing data in modeling to create a PFSeS. CONCLUSIONS: Development of a PFSeS that is predicated on billing data would improve researchers' ability to assess the functional status of children who receive inpatient rehabilitation care for a neurologic injury or illness. An expert clinician panel, representing the spectrum of medical and rehabilitative care, indicated that proposed statistical modeling identifies relevant codes mapped to 3 important domains: self-care, mobility, and cognition/communication.

Prehospital Recognition and Management of Pediatric Sepsis: A Qualitative Assessment.

BACKGROUND AND PURPOSE: Sepsis is a life-threatening disease in children and is a leading cause of morbidity and mortality. Early prehospital recognition and management of children with sepsis may have significant effects on the timely resuscitation of this high-risk clinical condition. However, the care of acutely ill and injured children in the prehospital setting can be challenging. This study aims to understand barriers, facilitators, and attitudes regarding recognition and management of pediatric sepsis in the prehospital setting. METHODS: This was a qualitative study of EMS professionals participating in focus groups using a grounded theory-based design to gather information on recognition and management of septic children in the prehospital setting. Focus groups were held for EMS administrators and medical directors. Separate focus groups were held for field clinicians. Focus groups were conducted via video conference until saturation of ideas was reached. Using consensus methodology, transcripts were coded in an iterative process. Data were then organized into positive and negative factors based on the validated PRECEDE-PROCEED model for behavioral change. RESULTS: Thirty-eight participants in six focus groups identified nine environmental factors, 21 negative factors, and 14 positive factors pertaining to recognition and management of pediatric sepsis. These findings were organized into the PRECEDE-PROCEED planning model. Pediatric sepsis guidelines were identified as positive factors when they did exist and negative factors when they were complicated or did not exist. Six interventions were identified by participants. These include raising awareness of pediatric sepsis, increasing pediatric education, receiving feedback on prehospital encounters, increasing pediatric exposure and skills training, and improving dispatch information. CONCLUSION: This study fills a gap by examining barriers and facilitators to prehospital diagnosis and management of pediatric sepsis. Using the PRECEDE-PROCEED model, nine environmental factors, 21 negative factors, and 14 positive factors were identified. Participants identified six interventions that could create the foundation to improve prehospital pediatric sepsis care. Policy changes were suggested by the research team based on the results of this study. These interventions and policy changes provide a roadmap for improving care in this population and lay the groundwork for future research.

Pediatric Emergency Care Coordination in EMS Agencies: Findings of a Multistate Learning Collaborative.

BACKGROUND: In 2017, the Health Resources and Services Administration's Maternal Child and Health Bureau's Emergency Medical Services for Children program implemented a performance measure for State Partnership grants to increase the percentage of EMS agencies within each state that have designated individuals who coordinate pediatric emergency care, also called a pediatric emergency care coordinator (PECC). The PECC Learning Collaborative (PECCLC) was established to identify best practices to achieve this goal. This study's objective is to report on the structure and outcomes of the PECCLC conducted among nine states. METHODS: This study used quantitative and qualitative methods to evaluate outcomes from the PECCLC. Participating state representatives engaged in a 6-month collaborative that included monthly learning sessions with subject matter experts and support staff and concluded with a two-day in-person meeting. Outcomes included reporting the number of PECCs recruited, identifying barriers and enablers to PECC recruitment, characterizing best practices to support PECCs, and identifying barriers and enablers to enhance and sustain the PECC role. Outcomes were captured by self-report from participating state representatives and longitudinal qualitative interviews conducted with representative PECCs at 6 and 18 months after conclusion of the PECCLC. RESULTS: During the 6-month collaborative, states recruited 341 PECCs (92% of goal). Follow up at 5 months post-collaborative revealed an additional recruitment of 184 for a total of 525 PECCs (142% of the goal). Feedback from state representatives and PECCs revealed the following barriers: competition from other EMS responsibilities, budgetary constraints, lack of incentive for agencies to create the position, and lack of requirement for establishing the role. Enablers identified included having an EMS agency recognition program that includes the PECC role, train-the-trainer programs, and inclusion of the PECC role in agency licensure requirements. Longitudinal interviews with PECCs identified that the most common activity associated with their role was pediatric-specific education and the most important need for PECC success was agency-level support. CONCLUSION: Over the 6-month Learning Collaborative, nine states were successful in recruiting a substantial number of PECCs. Financial and time constraints were significant barriers to statewide PECC recruitment, yet these can be potentially addressed by EMS agency recognition programs.

Impact of Race and Ethnicity on Emergency Medical Services Administration of Opioid Pain Medications for Injured Children.

BACKGROUND: Treatment with analgesics for injured children is often not provided or delayed during prehospital transport. OBJECTIVE: Our aim was to evaluate racial and ethnic disparities with the use of opioids during transport of injured children. METHODS: We conducted a prospective study of injured children transported to 1 of 10 emergency departments from July 2019 to April 2020. Emergency medical services (EMS) providers were surveyed about prehospital pain interventions during transport. Our primary outcome was the use of opioids. We performed multivariate regression analyses to evaluate the association of patient demographic characteristics (race, ethnicity, age, and gender), presence of a fracture, EMS provider type (Advanced Life Support [ALS] or non-ALS) and experience (years), and study site with the use of opioids. RESULTS: We enrolled 465 patients; 19% received opioids during transport. The adjusted odds ratios (AORs) for Black race and Hispanic ethnicity were 0.5 (95% CI 0.2-1.2) and 0.4 (95% CI 0.2-1.3), respectively. The presence of a fracture (AOR 17.0), ALS provider (AOR 5.6), older patient age (AOR 1.1 for each year), EMS provider experience (AOR 1.1 for each year), and site were associated with receiving opioids. CONCLUSIONS: There were no statistically significant associations between race or ethnicity and use of opioids for injured children. The presence of a fracture, ALS provider, older patient age, EMS provider experience, and site were associated with receiving opioids.

Use of Antifibrinolytics in Pediatric Life-Threatening Hemorrhage: A Prospective Observational Multicenter Study.

OBJECTIVES: To assess the impact of antifibrinolytics in children with life-threatening hemorrhage. DESIGN: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four children's hospitals in the United States, Canada, and Italy. PATIENTS: Children 0-17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol. INTERVENTION/EXPOSURE: Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2-15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 [95% CI, 0.09-0.93]; p = 0.04 and adjusted odds ratio, 0.45 [95% CI, 0.21-0.98]; p = 0.04, respectively). CONCLUSIONS: Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage.

Implementation of an Automated Sepsis Screening Tool in a Children's Hospital Emergency Department: A Cost Analysis.

OBJECTIVE: To determine the effect of implementation of an automated sepsis screening tool on the median cost of affected patient encounters. STUDY DESIGN: This retrospective cohort study used propensity score-matched comparison groups to assess the difference in median cost for comparable affected patient encounters before and after the implementation of an automated sepsis screening tool in a large US children's hospital emergency department (ED) with >90 000 annual visits. All patient encounters in 2018 impacted by the automated sepsis screening tool were included and compared with a propensity score-matched comparison group drawn from patient encounters in 2012 that might have been affected by the screening tool had it been active at that time. The main outcome was the change in the median cost for comparable affected patient encounters. RESULTS: The overall median cost for those affected by an automated sepsis screening tool decreased by 21.2%, from $6454 (IQR, $968-$21 697) to $5084 (IQR, $802-$16 618). The median cost for encounters with an associated International Classification of Diseases sepsis code decreased by 51.1%, from $58 685 (IQR, $32 224-$134 895) to $28 672 (IQR, $16 796-$60 657). CONCLUSIONS: The median cost for comparable patient encounters decreased with implementation of an automated sepsis screening tool in the pediatric ED. Costs were decreased even more substantially for patients with sepsis. In addition to improving outcomes, an automated sepsis screening tool appears to be at least cost-effective and may be cost-saving, an incentive for more widespread use of this technology.

Association of Economic Recession and Social Distancing With Pediatric Non-accidental Trauma During COVID-19.

INTRODUCTION: There has been concern that the incidence of non-accidental trauma (NAT) cases in children would rise during the COVID-19 pandemic due to the combination of social isolation and economic depression. Our goal was to evaluate NAT incidence and severity during the pandemic across multiple US cities. METHODS: Multi-institutional, retrospective cohort study comparing NAT rates in children <18 y old during the COVID-19 pandemic (March-August 2020) with a recent historical data (January 2015-February 2020) and during a previous economic recession (January 2007-December 2011) at level 1 Pediatric Trauma Centers. Comparisons were made in local and national macroeconomic indicators. RESULTS: Overall rates of NAT during March-August 2020 did not increase compared to historical data (P = 0.8). Severity of injuries did not increase during the pandemic as measured by Glasgow Coma Scale (GCS) (P = 0.97) or mortality (P = 0.7), but Injury Severity Score (ISS) slightly decreased (P = 0.018). Racial differences between time periods were seen, with increased proportions of NAT occurring in African-Americans during the pandemic (P < 0.001). NAT rates over time had low correlation (r = 0.32) with historical averages, suggesting a difference from previous years. Older children (≥3 y) had increased NAT rates during the pandemic. Overall NAT rates had low inverse correlation with unemployment (r = -0.37) and moderate inverse correlation with the stock market (r = -0.6). Significant variation between sites was observed. CONCLUSIONS: Overall NAT rates in children did not increase during the COVID-19 pandemic, but rates were highly variable by site and increases were seen in African-Americans and older children. Further studies are warranted to explore local influences on NAT rates.

Transfusion Ratios and Deficits in Injured Children With Life-Threatening Bleeding.

OBJECTIVES: To assess the impact of plasma and platelet ratios and deficits in injured children with life-threatening bleeding. DESIGN: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four childrens hospitals in the United States, Canada, and Italy. PATIENTS: Injured children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under activation of massive transfusion protocol. INTERVENTION/EXPOSURE: Weight-adjusted blood product volumes received during the bleeding event were recorded. Plasma:RBC ratio (plasma/RBC weight-adjusted volume in mL/kg) and platelet:RBC ratio (platelet/RBC weight-adjusted volume in mL/kg) were analyzed. Plasma deficit was calculated as RBC mL/kg - plasma mL/kg; platelet deficit was calculated as RBC mL/kg - platelet mL/kg. MEASUREMENTS AND MAIN RESULTS: Of 191 patients analyzed, median (interquartile range) age was 10 years (5-15 yr), 61% were male, 61% blunt mechanism, and median (interquartile range) Injury Severity Score was 29 (24-38). After adjusting for Pediatric Risk of Mortality score, cardiac arrest, use of vasoactive medications, and blunt mechanism, a high plasma:RBC ratio (> 1:2) was associated with improved 6-hour survival compared with a low plasma:RBC ratio (odds ratio [95% CI] = 0.12 [0.03-0.52]; p = 0.004). Platelet:RBC ratio was not associated with survival. After adjusting for age, Pediatric Risk of Mortality score, cardiac arrest, and mechanism of injury, 6-hour and 24-hour mortality were increased in children with greater plasma deficits (10% and 20% increased odds of mortality for every 10 mL/kg plasma deficit at 6 hr [p = 0.04] and 24 hr [p = 0.01], respectively); 24-hour mortality was increased in children with greater platelet deficits (10% increased odds of 24-hr mortality for every 10 mL/kg platelet deficit [p = 0.02)]). CONCLUSIONS: In injured children, balanced resuscitation may improve early survival according to this hypothesis generating study. Multicenter clinical trials are needed to assess whether clinicians should target ratios and deficits as optimal pediatric hemostatic resuscitation practice.

A Novel Use of NEMSIS to Create a PECARN-Specific EMS Patient Registry.

Background: Research networks need access to EMS data to conduct pilot studies and determine feasibility of prospective studies. Combining data across EMS agencies is complicated and costly. Leveraging the National EMS Information System (NEMSIS) to extract select agencies' data may be an efficient and cost-effective method of providing network-level data. Objective: Describe the process of creating a Pediatric Emergency Care Applied Research Network (PECARN) specific NEMSIS data set and determine if these data were nationally representative. Methods: We established data use agreements (DUAs) with EMS agencies participating in PECARN to allow for agency identification through NEMSIS. Using 2019 NEMSIS version 3.4.0 data for EMS events with patients 18 years old and younger, we compared PECARN NEMSIS data to national NEMSIS data. Analyzed variables were selected for their ability to characterize events. No statistical analyses were utilized due to the large sample, instead, differences of ±5% were deemed clinically meaningful. Results: DUAs were established for 19 EMS agencies, creating a PECARN data set with 305,188 EMS activations of which 17,478 (5.7%) were pediatric. Of the pediatric activations, 17,140 (98.1%) were initiated through 9-1-1 and 9,487 (55.4%) resulted in transport by the documenting agency. The national data included 36,288,405 EMS activations of which 2,152,849 (5.9%) were pediatric. Of the pediatric activations 1,704,141 (79.2%) were initiated through 9-1-1 and 1,055,504 (61.9%) were transported by the documenting agency. Age and gender distributions were similar between the two groups, but the PECARN-specific data under-represents Black and Latinx patients. Comparison of EMS provider primary impressions revealed that three of the five most common were similar with injury being the most prevalent for both data sets along with mental/behavioral health and seizure. Conclusion: We demonstrated that NEMSIS can be leveraged to create network specific data sets. PECARN's EMS data were similar to the national data, though racial/ethnic minorities and some primary impressions may be under-represented. Additionally, more EMS activations in PECARN study areas originated through 9-1-1 but fewer were transported by the documenting agency. This is likely related to the type of participating agencies, their ALS response level, and the diversity of the communities they serve.

Life-Threatening Bleeding in Children: A Prospective Observational Study.

OBJECTIVES: The purpose of our study was to describe children with life-threatening bleeding. DESIGN: We conducted a prospective observational study of children with life-threatening bleeding events. SETTING: Twenty-four childrens hospitals in the United States, Canada, and Italy participated. SUBJECTS: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included. INTERVENTIONS: Children were compared according bleeding etiology: trauma, operative, or medical. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours. CONCLUSIONS: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.

Cost Analysis of Emergency Department Criteria for Evaluation of Febrile Infants Ages 29 to 90 Days.

OBJECTIVE: To compare the medical costs associated with risk stratification criteria used to evaluate febrile infants 29-90 days of age. STUDY DESIGN: A cost analysis study was conducted evaluating the Boston, Rochester, Philadelphia, Step-by-Step, and PECARN criteria. The percentage of infants considered low risk and rates of missed infections were obtained from published literature. Emergency department costs were estimated from the Centers for Medicare and Medicaid Services. The Health Care Cost and Utilization Project databases were used to estimate the number of infants ages 29-90 days presenting with fever annually and costs for admissions related to missed infections. A probabilistic Markov model with a Dirichlet prior was used to estimate the transition probability distributions for each outcome, and a gamma distribution was used to model costs. A Markov simulation estimated the distribution of expected annual costs per infant and total annual costs. RESULTS: For low-risk infants, the mean cost per infant for the criteria were Rochester: $1050 (IQR $1004-$1092), Philadelphia: $1416 (IQR, $1365-$1465), Boston: $1460 (IQR, $1411-$1506), Step-by-Step $942 (IQR, $899-$981), and PECARN $1004 (IQR, $956-$1050). An estimated 18 522 febrile 1- to 3-month-old infants present annually and estimated total mean costs for their care by criteria were: Rochester, $127.3 million (IQR, $126.1-$128.5); Philadelphia, $129.9 million (IQR, $128.7-$131.1); Boston, $128.7 million (IQR, $127.5-$129.9); Step-by-Step, $ 126.6 million (IQR, $125.4-$127.8); and PECARN, $125.8 million (IQR, $124.6-$127). CONCLUSIONS: The Rochester, Step-by-step, and PECARN criteria are the least costly when evaluating infants 29-90 days of age with a fever.

Survey to inform trial of low-titer group O whole-blood compared to conventional blood components for children with severe traumatic bleeding.

BACKGROUND: Low-titer group O whole-blood (LTOWB) is being used for children with life-threatening traumatic bleeding. A survey was conducted to determine current LTOWB utilization and interest in participation in a randomized control trial (RCT) of LTOWB versus standard blood component transfusion in this population. STUDY DESIGN AND METHODS: Transfusion medicine (TM) directors and pediatric trauma directors at 36 US children's hospitals were surveyed by e-mail in June 2020. Hospitals were selected by participation in the Massive Transfusion Epidemiology and Outcomes in Children Study or being among the largest 30 children's hospitals by bed capacity per the Becker Hospital Review. RESULTS: The response rate was 83.3% (30/36) from TM directors and 88.9% (32/36) from trauma directors. The median of massive transfusion protocol activations for traumatic bleeding was reported as 12 (IQR 5.8-20) per year by TM directors. LTOWB was used by 18.8% (6/32) of trauma directors. Survey responses indicate that 86.7% (26/30) of TM directors and 90.6% (29/32) of trauma directors either moderately or strongly agree that a LTOWB RCT is important to perform. About 83.3% (25/30) of TM directors and 93.8% (30/32) of trauma directors were willing to participate in the proposed trial. About 80% (24/30) of TM directors and 71.9% (23/32) of trauma directors would transfuse RhD+ LTOWB to male children, but fewer would transfuse Rh + LTOWB to females [20% (6/30) TM directors and 37.5% (12/32) of trauma directors]. CONCLUSIONS: A majority of respondents supported an RCT comparing LTOWB to component therapy in children with severe traumatic bleeding.