Massive Transfusion in Pediatric Patients on Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Massive Transfusion in Children (MATIC) Study.

Few data describe pediatric patients who receive massive transfusion for life-threatening hemorrhage (LTH) while on extracorporeal membrane oxygenation (ECMO). We present a retrospective secondary analysis of a multicenter prospective observational study to describe resource utilization and mortality in pediatric patients with LTH while on ECMO. Children who were on ECMO during an LTH were compared to children with LTH who were not on ECMO. Primary outcomes were volumes of blood products administered and 28 day mortality. Comparisons were assessed by two-sided Fisher's exact test or Wilcoxon rank sum test. A total of 449 children, including 36 on ECMO, were included. Compared to those not on ECMO, children on ECMO received a higher volume of blood products (110 [50-223] vs. 59 [28-113]) ml/kg, p = 0.002) and were more likely to receive antifibrinolytic therapy (39% vs. 10%, p < 0.001). Blood product ratios were similar. Extracorporeal membrane oxygenation patients had higher 28 day mortality (64% vs. 35%, p = 0.001), although 24 hour mortality was similar (17% vs. 23%, p = 0.5). In conclusion, children on ECMO with LTH experience high resource utilization and 28 day mortality. Studies are needed to identify children at risk for LTH and to evaluate ECMO-specific treatment strategies.

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.

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.

Identifying Children at Risk for Maltreatment Using Emergency Medical Services' Data: An Exploratory Study.

The objective of this study was to use natural language processing to query Emergency Medical Services (EMS) electronic health records (EHRs) to identify variables associated with child maltreatment. We hypothesized the variables identified would show an association between the Emergency Medical Services encounter and risk of a children maltreatment report. This study is a retrospective cohort study of children with an EMS encounter from 1/1/11-12/31/18. NLP of EMS EHRs was conducted to generate single words, bigrams and trigrams. Clinically plausible risk factors for child maltreatment were established, where presence of the word(s) indicated presence of the hypothesized risk factor. The EMS encounters were probabilistically linked to child maltreatment reports. Univariable associations were assessed, and a multivariable logistic regression was conducted to determine a final set of predictors. 11 variables showed an association in the multivariable modeling. Sexual, abuse, chronic condition, developmental delay, unconscious on arrival, criminal activity/police, ingestion/inhalation/exposure, and <2 years old showed positive associations with child maltreatment reports. Refusal and DOA/PEA/asystole held negative associations. This study demonstrated that through EMS EHRs, risk factors for child maltreatment can be identified. A future direction of this work include developing a tool that screens EMS EHRs for households at risk for maltreatment.

Pediatric emergency department visits for pedestrian injuries in relation to the enactment of Complete Streets policy.

Introduction: This study aimed to evaluate the rate of pediatric emergency department (ED) visits for pedestrian injuries in relation to the enactment of the Complete Streets policy. Methods: The National Complete Streets policies were codified by county and associated with each hospital's catchment area and date of enactment. Pedestrian injury-related ED visits were identified across 40 children's hospitals within the Pediatric Health Information System (PHIS) from 2004 to 2014. We calculated the proportion of the PHIS hospitals' catchment areas covered by any county policy. We used a generalized linear model to assess the impact of the proportion of the policy coverage on the rate of pedestrian injury-related ED visits. Results: The proportion of the population covered by Complete Streets policies increased by 23.9%, and pedestrian injury rates at PHIS hospitals decreased by 29.8% during the study period. After controlling for years, pediatric ED visits for pedestrian injuries did not change with increases in the PHIS catchment population with enacted Complete Streets policies. Conclusion: After accounting for time trends, Complete Streets policy enactment was not related to observed changes in ED visits for pedestrian injuries at PHIS hospitals.

Decision-making for pediatric cervical spine imaging after blunt trauma: Investigating team dynamics in the emergency department.

Objective: Cervical spine imaging decision-making for pediatric traumas is complex and multidisciplinary. Implementing a risk assessment tool has the potential to reduce variation in these decisions and unnecessary radiation exposure for pediatric patients. We sought to determine how emergency department-trauma team dynamics may affect implementation of such a tool. Methods: We interviewed (pediatric and general emergency physicians, trauma surgeons, neurosurgeons, orthopedic surgeons and ED nurses at 21 hospitals to ascertain how team dynamics affect the pediatric cervical spine imaging decision-making process. Data were coded following a framework-driven deductive coding process and thematic analysis was used. Results: Forty-eight physicians, advanced practice providers, and nurses from 21 hospitals (inclusive of three US regions, trauma levels I-III, and serving towns/cities of various population sizes) were interviewed. Overall, emergency physicians and trauma surgeons indicate being generally responsible for pediatric cervical spine imaging decisions. Conflict often occurs between these specialties due to differential weighting of concerns for missing an injury versus avoiding radiation exposure. Participants described a lack of trust and unclear roles regarding ownership for the final imaging decision. Nurses commonly described low psychological safety that prohibits them from participating in the decision-making process. Conclusions: Implementation of a standardized risk assessment tool for cervical spine trauma imaging decisions must consider perspectives of both emergency medicine and trauma. Policies to define appropriate use of standardized tools within this team environment should be developed.

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.

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.

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.

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.

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.

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.

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.

Pediatric traumatic hemorrhagic shock consensus conference recommendations.

ABSTRACT: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

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.

Pediatric traumatic hemorrhagic shock consensus conference research priorities.

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock. METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting. RESULTS: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area. CONCLUSION: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock.