Are we over activating Massive Hemorrhage Protocols in Pediatric Patients?

Dylan Grimm¹, Laurence Delorme¹, Eric Fagan¹, Na Li ², Mark McVey^3,4, Suzanne Beno^5,6, Elaine Leung^7,8, Lani Lieberman^9,10, Troy Thompson¹¹, Katerina Pavenski¹², Jeannie Callum¹³, Kimmo Murto^14,15

¹Queen’s University, Faculty of Medicine, Kingston, ON; ²Centre for Health Informatics, University of Calgary, Calgary, AB; ³Hospital for Sick Children, Toronto, ON; ⁴Assistant Professor, University of Toronto, Department of Anesthesiology & Pain Medicine, Toronto, ON; ⁵Associate Professor, University of Toronto, Department of Pediatrics, Division of Emergency Medicine, Toronto, ON; ⁶Hospital for Sick Children, Toronto, ON; ⁷Assistant Professor, University of Ottawa Department of Pathology and Laboratory Medicine, Division of Hematology and Transfusion Medicine, Ottawa, ON; ⁸Children’s Hospital of Eastern Ontario (CHEO), Ottawa, ON; ⁹Assistant Professor, University of Toronto, Department of Laboratory Medicine & Pathology, Toronto, ON; ¹⁰University Health Network: Toronto General Hospital, Toronto, ON; ¹¹Ontario Regional Blood Coordinating Network, Toronto, ON; ¹²Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; ¹³Professor, Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON; ¹⁴Associate Professor, University of Ottawa, Department of Anesthesiology & Pain Medicine, Ottawa, ON; ¹⁵CHEO Research Institute, Ottawa, ON.

Hemorrhage is the leading cause of preventable death within the first 24 hours after trauma in children and adults. In May 2021, the Ontario Regional Blood Coordinating Network (ORBCoN) disseminated the first provincial pediatric and adult evidence-based massive-hemorrhage-protocol (MHP) and associated toolkit content including recommendations for 8 quality improvement (QI) metrics.^1,2 The initial QI data have provided insight on MHP trends in Ontario hospitals, and highlighted differences between adult and pediatric MHP activations.
MHP activation data and 28 day follow-up from 8 Ontario hospitals including 2 pediatric tertiary care centers was retrospectively collected (January 2019-May 2022). Patient demographics, mortality rates and 8 MHP QI metrics were entered in REDCap© data-collection-tool, and differences between adult versus pediatric MHP quality metrics were assessed.

In total, 363 MHP activations were reported and available for comparison (44 pediatric, 319 adult) (Table 1). Hemorrhage from traumatic injury accounted for most activations in children (59%) and adults (40%). Analysis of the QI metrics (Table 2) showed children were more likely to experience MHP over-activation (66 vs. 39%, p=0.002; correct activation defined as blood component requirements of adults>6 RBC units; children> 40 ml/kg, or death due to bleeding within first 24-hours) and less likely to experience a delay in RBC transfusion (4.5 vs 13%, p=0.003 (defined as > 15 minutes from protocol activation). Both cohorts reported ≥ 20% of patients had delayed tranexamic acid (TXA) administration and both cohorts had 11% of patients with uncorrected hypothermia at MHP termination. RBC over-transfusion (Hgb>110 g/L at MHP termination) was common and reported in 45% and 31% of children and adults, respectively, and 9.1% and 16% in children and adults reported blood component wastage.

MHP over-activation was more common in children compared with adults, with pediatric patients tending to see more unecessary activations as well as over-transfusions. One possible explanation is that hemorrhagic shock in pediatric patients may have a delayed onset or be more challenging to diagnose. However, these concerns should be balanced against transfusion risks, including hyperkalemia, hypoglycemia, and circulatory overload. In both cohorts, timely administration of TXA and management of hypothermia should be improved, as both have been shown to improve mortality in hemorrhage.

One limitation of this analysis is low numbers of pediatric MHP activations. However, at the time of this newsletter publication, there will be approximately 1700 MHP activations collected in the RedCAP® system, around 100 of which are expected to be pediatric activations. The data analysis is ongoing. The MHP QI metrics system is a valuable tool to identify the areas of improvement, with an overall goal of improving outcomes in patients receiving MHP.

Table 1. Demographics of pediatric and adult massive hemorrhage protocal activation cohorts

Table 2: Comparison of pediatric with adult massive hemorrhage protocol quality indicators, years 2019-2022

References:

1. Callum JL, Yeh CH, Petrosoniak A, et al. A regional massive hemorrhage protocol developed through a modified Delphi technique. CMAJ. 2019;7(3):E546-E561.
2. Cope S, Callum J, Pavenski K, et al. Ontario’s Massive Hemorrhage Toolkit. Transfus Med Rev. 2022;36(1):67.
3. Holcomb JB, Moore EE, Sperry JL, et al. Evidence-Based and Clinically Relevant Outcomes for Hemorrhage Control Trauma Trials. Ann Surg. 2021;273(3):395-401.
4. Leonard JC, Josephson CD, Luther JF, et al. Life-Threatening Bleeding in Children: A Prospective Observational Study. Crit Care Med. 2021;49(11):1943-1954.

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