Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations

Robert T Russell; Joseph R Esparaz; Michael A Beckwith; Peter J Abraham; Melania M Bembea; Matthew A Borgman; Randall S Burd; Barbara A Gaines; Mubeen Jafri; Cassandra D Josephson; Christine Leeper; Julie C Leonard; Jennifer A Muszynski; Kathleen K Nicol; Daniel K Nishijima; Paul A Stricker; Adam M Vogel; Trisha E Wong; Philip C Spinella

doi:10.1097/TA.0000000000003805

. Author manuscript; available in PMC: 2024 Jan 1.

Published in final edited form as: J Trauma Acute Care Surg. 2022 Oct 17;94(1):S2–S10. doi: 10.1097/TA.0000000000003805

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Recommendations

Robert T Russell ¹, Joseph R Esparaz ¹, Michael A Beckwith ², Peter J Abraham ³, Melania M Bembea ⁴, Matthew A Borgman ⁵, Randall S Burd ⁶, Barbara A Gaines ⁷, Mubeen Jafri ⁸, Cassandra D Josephson ⁹, Christine Leeper ¹⁰, Julie C Leonard ¹¹, Jennifer A Muszynski ¹², Kathleen K Nicol ¹³, Daniel K Nishijima ¹⁴, Paul A Stricker ¹⁵, Adam M Vogel ¹⁶, Trisha E Wong ¹⁷, Philip C Spinella ¹⁸

¹Department of Surgery, Division of Pediatric Surgery, University of Alabama at Birmingham, Children’s of Alabama, Birmingham, AL

²Department of Surgery, Division of Pediatric Surgery, University of Michigan, Ann Arbor, MIS

³Department of Surgery, University of Alabama at Birmingham, Birmingham, AL

⁴Division of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD

⁵Department of Pediatrics, Brooke Army Medical Center, Uniformed Services University

⁶Division of Trauma and Burn Surgery, Children’s National Hospital, Washington, DC

⁷Department of Surgery, University of Pittsburgh School of Medicine, UPMC Children’s Hospital, Pittsburgh, PA.

⁸Division of Pediatric Surgery, Doernbecher Children’s Hospital, Oregon Health and Science University, Portland, OR

⁹Departments of Pathology and Laboratory Medicine and Pediatrics, Emory University School of Medicine, Atlanta, GA

¹⁰Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA.

¹¹Department of Pediatrics, Division of Emergency Medicine, The Ohio State University College of Medicine, Nationwide Children’s Hospital, Columbus, OH

¹²Division of Critical Care Medicine, The Ohio State University College of Medicine, Nationwide Children’s Hospital, Columbus, OH

¹³Department of Pathology and Laboratory Medicine, The Ohio State University College of Medicine Nationwide Children’s Hospital, Columbus, OH.

¹⁴Department of Emergency Medicine, University of California, Davis School of Medicine, Sacramento, CA.

¹⁵Department of Anesthesiology and Critical Care, The Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA

¹⁶Divisions of Pediatric Surgery and Critical Care, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX.

¹⁷Division of Pediatric Hematology and Oncology and Department of Pathology, Oregon Health & Science University, Portland, OR

¹⁸Department of Surgery and Critical Care Medicine, University of Pittsburgh Medical Center. Pittsburgh, PA.

Author Contributions: RR, JE, MB, and PA reviewed abstracts and full-text articles for the topic literature reviews. RR, MMB, MAB, DN, PS, AV, CL and MJ drafted portions of the manuscript and RR synthesized the manuscript. All authors reviewed the reviewed, edited, and approved the manuscript prior to final submission.

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Corresponding Author: Robert T. Russell, MD, MPH, University of Alabama at Birmingham, Children’s of Alabama, 1600 7^th Avenue South, Suite 300, Birmingham, AL 35233, 205-638-9699, robert.russell@childrensal.org

PMCID: PMC9805499 NIHMSID: NIHMS1841015 PMID: 36245074

Summary

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 (PTHSCC) 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 six specific topics: 1) blood products and fluid resuscitation for hemostatic resuscitation, 2) utilization of pre-hospital blood products, 3) use of hemostatic adjuncts, 4) tourniquet use, 5) pre-hospital airway and blood pressure management, 6) conventional coagulation tests or thromboelastography-guided resuscitation.

A total of 21 recommendations are detailed in this manuscript: 2 clinical recommendations, 14 expert consensus statements and 5 good practice statements. The statement, the panel’s voting outcome, 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 PTHSCC systematically evaluated the literature, developed clinical recommendations, expert consensus and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Level of Evidence:

N/A

Keywords: trauma, pediatrics, hemorrhage, consensus

Media Summary:

Hemorrhagic shock remains a preventable cause of death in pediatric trauma patients. Based on systematic literature reviews, this manuscript discusses clinical recommendations, expert consensus statements, and good practice statements for the care of pediatric patients in traumatic hemorrhagic shock.

Graphical Abstract

graphic file with name nihms-1841015-f0001.jpg

Introduction

Trauma is the leading cause of pediatric mortality, potential years of life lost, and a significant medical cost in the developed world.^{1, 2} Thirty day mortality in children with traumatic hemorrhagic shock is 36–50% compared to 20–25% reported in adults.^{3, 4} An estimated 1,000–2,000 preventable traumatic deaths in children per year after injury occur in the United States due to inadequate or delayed care.⁵ Recent retrospective and prospective observational studies indicate that transfusion strategies (limiting crystalloid, appropriate transfusion ratios, and use of whole blood) and intravenous hemostatic adjunct therapies can reduce morbidity and mortality in children with traumatic hemorrhagic shock.^6–9 For this reason, hemostatic strategies represent a key target for standardization and subsequent investigation. However due to the lack of high-quality clinical trials to guide practice, hemostatic resuscitation strategies and the utilization of global assays of hemostasis for goal directed therapy are highly variable across sites.^{10, 11} There is also a lack of agreement upon critical definitions of pediatric massive transfusion, definition of coagulopathy and critical common data elements required for clinical trial design. To address these challenges, we organized a multidisciplinary team of experts and key stakeholders to: 1) develop consensus statements on best practice in resuscitation strategies for pediatric trauma patients experiencing hemorrhagic shock based on the current literature, 2) create a strategy, in collaboration with implementation experts, for adaptive dissemination and implementation into clinical and research environments, and 3) develop future research priorities for studying resuscitation practices for pediatric traumatic hemorrhagic shock and foster collaboration in pursuit of improved clinical care for these patients.

Methods

The methodology for the Pediatric Traumatic Hemorrhagic Shock Consensus Conference (PTHSCC) follow the standards set by the Institute of Medicine for developing comprehensive evidence-based recommendations. When evidence was lacking, the panel developed expert consensus statements and good practice statements for decision making in pediatric trauma patients experiencing hemorrhagic shock. The complete methods are in Appendix A and the good practice statements in Appendix B.

Clinical Recommendations (n=2) and Expert Consensus Statements (n= 14):

1). Blood products and fluid resuscitation in pediatric traumatic hemorrhagic shock

1.1: In traumatically injured children in hemorrhagic shock, we suggest prioritizing the use of blood products over the use of crystalloids for resuscitation. Consensus Panel Expertise, 100% agreement (n=16), median 9, IQR: 8–9.

Rationale:

During and after the Vietnam War, crystalloids and colloids replaced blood as the primary initial resuscitative solution for hemorrhagic shock. This change was in part due to logistic difficulties of using blood and the infectious disease risks of blood products. The shift to crystalloids was supported by research performed by Carrico et al. indicating that the interstitial compartment or “third space” needed to be resuscitated with 1 to 2 liters of crystalloids to perfuse the tissues. This research further recommended that the transfusion of whole blood (WB) would only be indicated if hemodynamic instability persisted following administration of crystalloids.¹² To the detriment of patients with severe bleeding, misinterpretation of these data contributed to overuse of crystalloids before any blood product were administered. When used in practice, this approach could result in dilutional coagulopathy and severe interstitial edema. A shift from early blood product administration to a preference for early crystalloid and colloid use led to an increase in acute respiratory distress syndrome, abdominal compartment syndrome, multiorgan failure, and anasarca in intensive care units (ICUs).¹³

These outcomes were predicted by Shoemaker in 1976¹⁴ when he challenged the notion that the interstitial compartment required resuscitation. He instead emphasized the need for whole blood (WB) to treat significant bleeding when the hematocrit fell below 30%. The overuse of crystalloids continued despite a call for changes in practice recommended by Moore and Shires as early as 1967. In an editorial, Moore and Shires state, “blood should still be replaced during major operative surgery as it is lost. The use of balanced salt solutions appears to be a physiological adjunct to surgical trauma, not a substitute for blood.” Subsequent research has demonstrated that a crystalloid-based resuscitation strategy leads to higher inflammation and vascular permeability compared to WB.¹⁴

Data supporting the use of blood products instead of crystalloids in children include a multicenter prospective observational study performed from April 2018 to Sept 2019.¹⁵ In this study of 712 children from 24 trauma centers, each crystalloid bolus after the first was incrementally associated with an increased odds of more mechanical ventilation and intensive care unit days and longer hospital stays. A longer time to initiate the first transfusion was also associated with more mechanical ventilation days. In another retrospective study of 512 children admitted to combat support hospitals between 2007 and 2016, the authors evaluated the association of high crystalloid use (> 40ml/kg in 24 hours) for patients receiving high or low plasma:RBC ratios (1:2 threshold).¹⁶ In children who received a high ratio of plasma:RBCs and low crystalloid volume, there was an independent association with improved survival (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.04–11.24). In contrast, children with a high ratio of plasma:RBCs with high crystalloid volumes was not associated with improved survival (OR 0.61; [ 0.28–1.29]). The authors concluded that the high crystalloid volume negated the potential survival benefit of high plasma:RBC ratios in children with severe traumatic bleeding.

A secondary analysis of the PAMPer trial showed similar findings. This study of injured adults compared four groups of patients based on prehospital resuscitation with PRBC and plasma, plasma only, PRBC only, and crystalloid only. For patients with severe traumatic bleeding, they found that the exclusive use of crystalloids worsened survival compared to the partial use of blood products in the prehospital resuscitation phase.¹⁷ A second RCT in adults with severe traumatic injury showed the use of crystalloids in the prehospital phase of resuscitation decreased the risk of survival compared to not using any crystalloids or blood products.¹⁸

Pediatric and adult data supports the association of crystalloids with worse outcomes and the increased and early use of blood products (whole blood or balanced approach) with improved survival. These data support our recommendation suggesting the prioritization of blood products over crystalloids for the resuscitation of traumatic hemorrhagic shock in children.

1.2: In traumatically injured children in hemorrhagic shock, the use of low titer (≤ 200 Ig G) group O whole blood might be considered if available over individual blood components (RBC, plasma, and platelets) for resuscitation. Clinical Recommendation, conditional recommendation, very low certainty of evidence, 94% agreement (n=16), Median 8.5, IQR: 7.75–9.

Rationale:

When compared to individual blood components in a balanced ratio, low titer group O whole blood (LTOWB) is more potent due to less anticoagulants, less preservatives increasing hemoglobin, platelet concentrations, and coagulation factors.¹⁹ In addition, storage of platelets at 4°C may also make LTOWB more hemostatic. In addition, whole blood causes less dilutional coagulopathy and less hypocalcemia due to the increased citrate when transfusing multiple blood components.²⁰ Due to the exclusive use of a group O product, whole blood may be safer than use of components by preventing transfusion of incompatible ABO unit(s) that may lead to a fatal hemolytic reaction due to human error.²¹ In addition, the storage of whole blood at 4°C reduces the risk of bacterial contamination that exists with the use of platelets stored at room temperature.²² Finally, whole blood has logistic advantages due to the need to only dispense one product from the blood bank and administer one product at the bedside instead of dispensing and administering individual blood components.

Using LTOWB instead of individual blood components in children more rapidly provides RBCs, plasma and platelets to children with severe traumatic bleeding, more effectively resolves shock and coagulopathy,²³ is associated with less total amount of blood products administered and mechanical ventilation days,²⁴ and is independently associated with increased 72 hour (OR 0.23; [0.08–0.70]), and 28 day mortality (OR 0.41; [ 0.23–0.98]) in a single center retrospective study.⁸

Adult data indicates the use of LTOWB compared to individual blood components is independently associated with improved 24 hour and 28 day survival and is also associated with less (40–60%) total blood products administered.^25–27 Data from studies performed on children and adults suggest no increased risk of hemolysis in non-group O recipients and no increase in any other adverse outcomes to include organ failure.^28–30

1.3: In traumatically injured children in hemorrhagic shock, when utilizing blood component resuscitation, we suggest targeting high plasma:RBC ratios (1:1) to minimize the plasma deficit. Consensus Panel Expertise, 100% agreement (n=16), median 9, IQR: 8–9.

Rationale:

Children with life threatening hemorrhage from traumatic injuries develop shock due to hypoperfusion. This hypoperfusion causes endothelial injury with loss of the glycocalyx and increased endothelial permeability. The endothelial injury leads to inflammation which can further exacerbate endothelial injury and lead to the production of increased activated protein C and tissue plasminogen activator directly causing trauma induced coagulopathy. While this pathophysiology has been mainly described in adults, there is data indicating it may also occur in children.^31–33 Differences in hemostasis mechanisms between children and adults will require additional study to establish whether these mechanisms are also observed in children.³⁴ To address the shock, endothelial, immune and hemostatic dysfunction, a balanced resuscitation with plasma and RBCs may be optimal because plasma may repair the endothelium and mitigate capillary leak and improve intravascular volume. Plasma may also improve hemostasis by providing coagulation factors for patients who have developed a consumptive coagulopathy. These potential effects of plasma may improve intravascular volume, reduce extravascular edema and bleeding which can all lead to improved oxygen delivery.

A two-year retrospective review of the pediatric trauma quality improvement program (TQIP) supports that the increased plasma:RBC ratios minimize plasma deficit. In this study of over 500 massively transfused children, the plasma:RBC ratio, as a continuous variable, was associated with improved 24-hour mortality (OR 0.47; [0.28–0.80]). In this same study, a plasma:RBC ratio > 1:1 was also independently associated with reduced 24-hour mortality (OR 0.48; [0.26–0.88]). In a multi-institutional prospective observational study that included 191 children with traumatic injury and life-threatening hemorrhage, there was an independent association with a plasma:RBC ratio of > 1:2 with improved 24-hour survival (OR 0.36; [0.13–0.99]). When the plasma deficit (RBC ml/kg – plasma ml/kg) was analyzed, an increased deficit was also associated with increased 24 hour mortality (OR 1.2; [1.05–1.3]).⁴ Additional publications that do not report an association of increased plasma:RBC ratios with improved outcomes have significant limitations to include the lack of adjusted analyses and small sample size or single center studies.^{27, 35, 36} Adult data supporting the use of high ratios targeting 1:1 include the PROPPR trial that reported reduced death from bleeding at 24 hours and improved time to cessation of bleeding.³⁷ The PAMPer trial also reported improved survival when plasma was used early in the prehospital phase of resuscitation.³⁸

1.4: In traumatically injured children in hemorrhagic shock, when utilizing blood component resuscitation, targeting a high platelet to RBC weight-based ratio of 1:1 to minimize the platelet deficit is suggested. Consensus Panel Expertise, 100% agreement (n=16), median 8, IQR: 7–9.

Rationale:

Platelet dysfunction occurs early in traumatic blood failure in adults and the transfusion of platelets may reverse it.³⁷ The importance of the platelets within hemostasis is another reason to hypothesize that the use of platelets may reduce bleeding and improve outcomes. In addition, in vitro and animal evidence suggest that platelet transfusion may repair the injured endothelium, which could also improve outcomes.^{39, 40}

Data supporting the early use of platelets in children was also published in the aforementioned multi-institutional prospective observational study in children with life threatening bleeding. In this study, a platelet deficit (RBC ml/kg – platelet ml/kg) was independently associated with increased mortality at 24 hours (OR 1.1 [1.05–1.2]) but there was no survival advantage associated with the platelet: RBC ratio.⁴ A plausible explanation for this may be that the deficit more accurately reflects the lack of balance between platelets and RBCs more than a ratio which does not incorporate the magnitude of the imbalance. Additional adult data supporting the early use of platelets, a secondary analysis of PROPPR trial focusing on platelet transfusions, demonstrated improved survival in these patients who achieved a more balanced resuscitation.⁴¹

2). Pre-hospital blood products use in pediatric traumatic hemorrhagic shock

2.1: In traumatically injured children in hemorrhagic shock, it is reasonable to consider prehospital transfusion by out-of-hospital EMS for injured children based on product availability and clinical judgement. Consensus Panel Expertise, 100% agreement (n=16), median 8, IQR: 8–8.25.

Definition for purpose of this recommendation:

Out-of-hospital EMS is defined as all medical care for a trauma patient that occurs in a non-health care setting, including scene response and interhospital transfer.

Rationale:

Death due to bleeding most often occurs early after injury.⁴² Delays in time to transfusion are associated with increased mortality and increased time to hemostasis.⁴³ The rationale for prehospital transfusion is to shift resuscitation earlier to address blood loss, mitigate shock and coagulopathy, and ultimately reduce mortality and morbidity for injured patients.

Little high-quality evidence has defined the optimal approach to fluid resuscitation and transfusion by out-of-hospital EMS in children with hemorrhagic shock. The management of acute life-threatening bleeding has been studied almost exclusively in adult trauma, where early blood product use by out-of-hospital EMS providers has become an accepted and common practice. In military^44–46 and civilian^{38, 47} adult cohorts, the use of blood products as the first resuscitative fluid has been associated with improved survival. No studies to date have reported survival benefits of prehospital blood product transfusion in children.

The transfusion of blood products by out-of-hospital EMS providers is feasible and safe.^{48, 49} Data show that the LTOWB⁴⁹, red blood cells and plasma⁴⁸ under pediatric dosing protocols is feasible, acceptable to providers, and not associated with adverse transfusion-related events.⁵⁰ Only two studies have compared outcomes between matched pediatric cohorts who received blood products prehospital versus in-hospital. These studies are limited by sample size and moderate bias due to outcome measurement and confounding.^{50, 51} Though the studies were not adequately powered to detect a difference in mortality; authors did report that the prehospital transfusion groups did receive less in-flight crystalloid, had higher admission fibrinogen levels, and faster time to normalization of the international normalized ratio (INR).⁵¹ This recommendation has to take into account the ability of blood products and comfort level of the practice of regional Emergency Medical Services. However, the above literature suggests that there is evidence that this can be organized and safely utilized in pediatric trauma patients with hemorrhagic shock.

3). Use of tranexamic acid and other hemostatic adjuncts in pediatric traumatic hemorrhagic shock

3.1: In traumatically injured children with hemorrhagic shock, the empiric use of tranexamic acid within 3 hours of injury might be considered. Clinical Recommendation, conditional recommendation, very low certainty of evidence, 80% agreement (n=15), median 7, IQR: 7–8.

Rationale:

Fibrinolytic dysregulation is an important mechanism in traumatic coagulopathy that consists of a spectrum ranging from excessive breakdown (hyperfibrinolysis), physiologic fibrinolysis, and fibrinolytic shutdown. Injury to the vascular bed with endothelial disruption initiates a complex interaction between the endothelium, platelets, and coagulation factors ultimately resulting in thrombin generation and cross-linking of fibrin monomers. This interaction results in the formation of a mature clot, seals the area of vascular injury, and leads to hemostasis. Fibrinolysis is a physiologic process occurring in parallel with fibrin cross-linking to prevent the extension of this process beyond the injury. During injury, this process can turn from physiologic to pathologic to increased or reduced fibrinolysis, which have both been associated with high mortality.⁵² This increases the importance of timely identification and treatment of fibrinolytic dysregulation in trauma patients. Tranexamic acid (TXA), an antifibrinolytic agent, has been extensively studied in adult trauma trials in an effort to improve outcomes in patients with hyperfibrinolysis.^53–55 We did not identify any randomized clinical trials evaluating TXA in severely injured children. There were five observational studies (four retrospective and one prospective study) that compared empiric TXA use versus no TXA, controlling for confounders. Three of the studies were in civilian settings and two in combat settings. One combat associated paper evaluated a registry of 766 children of 9% received TXA.⁷ Using propensity score match analysis, they found that TXA was independently associated with a lower odds of mortality (OR 0.87; [0.85–0.89]). The second combat study, also evaluated a registry of children receiving massive transfusion, demonstrated that TXA use was associated with a lower odds of mortality (OR 0.35; [0.12–0.99]).⁵⁶ A prospective observational study of children with life-threatening bleeding showed that antifibrinolytic agents (TXA or aminocaproic acid) were associated with decreased 6 and 24 hour mortality (6 hour: adjusted OR 0.29; [0.09–0.93]; 24 hour: aOR 0.45; [0.21–0.98]) compared to those that received no antifibrinolytic agent ⁵⁷ Two retrospective studies did not find an association between TXA use and improved outcomes. One study evaluated a large administrative trauma database in Japan with a propensity matched analysis of children who did and did not receive TXA.⁵⁸ They found no difference in mortality between groups. However, based on a low mean ISS of 10, they may not have identified pediatric population most at risk for hemorrhagic shock. The second retrospective study evaluated massively transfused injured children and compared patients who received TXA to those who did not.⁵⁹ They found no mortality difference between groups, but this study had a small sample size (n=48).

There is strong evidence for empiric TXA in severely injured adults. The CRASH-2 randomized control trial randomized over 20,000 injured adults.⁶⁰ Compared to placebo, TXA decreased death from bleeding by one-third if given within 3 hours from injury. Several additional prospective adult randomized studies also have found a strong correlation of TXA administration with survival if given soon after injury, including when given to head injured patients.^61–63

3.2: In traumatically injured children with hemorrhagic shock, we recommend the use of tranexamic acid over aminocaproic acid when an antifibrinolytic agent is being considered. Consensus Panel Expertise, 93% agreement (n=15), median 8, IQR: 7–9.

Rationale:

No high-quality studies comparing TXA to aminocaproic acid have been published in a pediatric trauma population. However, a much broader body of adult and pediatric trauma and surgical literature exist to show the efficacy and safety of TXA than for aminocaproic acid.^{7, 53, 55, 56, 64–66} In addition, some data suggest an association between acute kidney injury and aminocaproic acid use in all children with life threatening bleeding.⁵⁷

3.3: In traumatically injured children with hemorrhagic shock, there is insufficient evidence for the empiric use of prothrombin concentrate. Consensus Panel Expertise, 93% agreement (n=15), median 9, IQR: 7–9.

Rationale:

Prothrombin complex concentrate (PCC), contains either three or four of the vitamin K-dependent coagulation factors (II, IX, X, and sometimes VII), and may be an alternative approach, to FFP, for correction of coagulopathy.⁶⁷ Although the literature is limited, adult literature in both trauma and operative settings support the administration of PCC to bleeding patients to reverse coagulopathy.^{68, 69} No high-quality studies evaluating the use PCC in a pediatric trauma population were identified. In a small retrospective study of a mixed pediatric population with only half experiencing trauma, PCC was found to improve INR but had no effect on outcomes.⁷⁰ While PCC is commonly used as a reversal agent in bleeding associated with vitamin K antagonists or direct oral anticoagulants, there is little clinical or physiologic evidence that PCC has any benefit as an empiric treatment for traumatically injured children in hemorrhagic shock.

3.4: In traumatically injured children with hemorrhagic shock, there is insufficient evidence that the use of viscoelastic monitoring to guide antifibrinolytic therapy improves patient outcomes. Consensus Panel Expertise, 94% agreement (n=16), median 7, IQR: 7–8.25.

Rationale:

Several studies have identified that children with hyperfibrinolysis have a higher mortality after injury.^{71, 72} Given this observation and the understanding of the antifibrinolytic effects of TXA, researchers would suggest that those children with hyperfibrinolysis should be identified and targeted for TXA.⁷³ Some pediatric trauma centers may utilize VEM to evaluate trauma patients for coagulopathy and fibrinolysis in addition to conventional coagulation testing. However, the selective use of TXA based on VEM has not been studied in children and the limited adult studies for rapid-thromboelastography (r-TEG) guided TXA administration have failed to show a clear benefit.⁷⁴ Until additional literature evaluates the specific utilization of VEM prior to and following administration of TXA in pediatric patients with different postinjury fibrinolysis subtypes, we cannot recommend use of VEM in this setting.

3.5: In traumatically injured children with hemorrhagic shock, there is insufficient evidence for the empiric use of fibrinogen supplementation (cryoprecipitate or fibrinogen concentrates). Consensus Panel Expertise, 87% agreement (n=15), median 7, IQR: 7–8.

Rationale:

No studies were identified supporting the empiric use of fibrinogen or cryoprecipitate in pediatric hemorrhagic trauma. There have been several adult studies investigating the use of fibrinogen supplementation, however a meta-analysis of these studies failed to show a mortality benefit.⁷⁵

3.6: In traumatically injured children with hemorrhagic shock, we suggest the replacement of fibrinogen in the setting of hypofibrinogenemia. Consensus Panel Expertise, 87% agreement (n=16), median 8, IQR: 8–9.

Rationale:

It is established that fibrinogen is an essential substrate for clot formation, and that low fibrinogen can lead to severe bleeding whether congenital or acquired.³¹ In the setting of trauma, low fibrinogen is essentially due to consumption. Most trauma centers will screen patients for hypofibrinogenemia, particularly during a massive transfusion, and correct if the fibrinogen level is below 150 mg/dL.⁷⁶ Low fibrinogen levels can be corrected either by the administration of fibrinogen concentrate or cryoprecipitate. VEM has been used to identify low fibrinogen, based on prolonged R time, low alpha angle, or low maximum amplitude. Rotational thromboelastometry can also be utilized. A pediatric study is underway studying early fibrinogen concentrate in pediatric patients presenting with a FIBTEM (extrinsically activated thromboelastometric test with cytochalasin D) A5 of <=10.⁷⁷ This study may provide us additional guidance for using of fibrinogen in pediatric trauma patients.

4). Use of tourniquets in pediatric traumatic hemorrhagic shock

4.1: In traumatically injured children with exsanguinating extremity hemorrhage, we recommend the use of commercially available tourniquets by individuals with training. Consensus Panel Expertise, 88% agreement (n=16), median 9, IQR: 7.75–9.

Rationale:

In the past, the use of tourniquets for exsanguinating extremity hemorrhage has had mixed impact on outcomes, mainly related to inappropriate applications by untrained responders. In earlier military conflicts, challenges with delays in reaching definitive care led to complications including the risk of limb loss.^{78, 79} Recent adult military experience with quicker transport times and enhanced training among soldiers/first responders showed a clear survival advantage among those with tourniquet use.⁸⁰ These data along with a dramatic increase in mass casualty events have influenced a paradigm shift among first responders in civilian settings toward tourniquet use.^81–84 Education of first responders has been advanced by a committed effort by the American College of Surgeons “Stop the Bleed’ program. Concerns remain regarding the applicability of combat adult practice with relation to children in civilian settings.

In these elective settings, tourniquet complications were found to occur in 0.4% to 1.4% of patients, with most injuries involving soft tissue or nerve damage.⁸⁵

Our review of available evidence for the use of tourniquets in exsanguinating extremity hemorrhage in children yielded six manuscripts: four from a military setting^86–89 and two evaluating a civilian experience.^{90, 91} These studies showed decreased crystalloid administration, decreased transfusion requirements and a survival advantage for children treated with tourniquets, particularly when applied before the onset of shock. There were no significant complications from tourniquet use. In the studies evaluated, challenges still exist with tourniquet use including tourniquet overuse, improper tourniquet application and a need for more standardized training.⁹⁰

5). Pre-hospital intubation and blood pressure management in pediatric traumatic hemorrhagic shock

5.1: In traumatically injured children with hemorrhagic shock, we suggest against a permissive hypotension strategy and suggest resuscitation goals that optimize end organ perfusion and adequate oxygen delivery. Consensus Panel Expertise, 93% agreement (n=15), median 7, IQR: 7–8.5.

Rationale:

Although some reports in the adult trauma literature suggest a potential benefit of permissive hypotension ^{92, 93}, this has become more controversial.^{94, 95} In pediatric trauma patients, there was insufficient evidence to evaluate this strategy. However, there is a widely accepted paradigm that children a significant ability to compensate until very late stages of hemorrhagic shock.⁹⁶ In Advanced Trauma Life Support (ATLS), the American College of Surgeons Committee on Trauma reports that a child has a low but normal blood pressure starting after 30% blood volume loss and experiences hypotension only after 45% blood volume loss.⁹⁷ Furthermore, a rigorous definition of permissive hypotension in pediatric patients could not be identified in the literature. Finally, in addition, injured children with hypotension may have a concomitant head injury for which permissive hypotension would not be a recommended strategy.

6). Resuscitation and use of hemostatic monitoring for pediatric traumatic hemorrhagic shock

6.1: In traumatically injured children with hemorrhagic shock, we suggest an initial empiric resuscitation approach utilizing massive transfusion protocols and balanced blood product administration. Consensus Panel Expertise, 94% agreement (n=16), median 9, IQR: 7–9.

Rationale:

In severely injured adult trauma patients, empiric hemostatic resuscitation using balanced blood products or whole blood as part of a massive transfusion protocol (MTP) is standard of care.^{98, 99} Although there have been many studies evaluating massively transfused children, a paucity of studies have critically examined the benefits of MTP implementation and use in children.¹⁰⁰ Three single center, retrospective studies specifically evaluated the impact of massive transfusion protocols on outcomes. A 2011 study compared 33 pre-MTP to 22 post-MTP children from a three-year period. The pre- and post-MTP groups included 31 and 16 trauma patients, respectively. Overall, there was no difference in mortality amongst the group even though the post-MTP implementation patients were more severely injured as assessed by injury severity score (ISS). The post-MTP group received more blood products and experienced less thromboembolic complications.¹⁰¹ A second 2011 study compared 53 MTP patients to 49 non-MTP patients over a two-year period. There were no differences in baseline characteristics including ISS. The MTP group received plasma earlier and received a more balanced resuscitation, but no difference in mortality was observed.¹⁰² Finally, a 2016 study compared 125 pre-MTP to 115 post-MTP implementation patients over a ten-year period. Despite the post-MTP cohort being more severely injured, there was no difference in mortality. Post-MTP patients received plasma and platelet transfusions earlier and in a more balanced ratio with red blood cells.¹⁰³ These studies suggest that massive transfusion protocols are safe and may provide benefit in the resuscitation of severely injured pediatric trauma patients in hemorrhagic shock.

6.2: In traumatically injured children with hemorrhagic shock, following empiric initial resuscitation, a goal directed resuscitation strategy to optimize hemostasis and correct coagulopathy is suggested. Consensus Panel Expertise, 100% agreement (n=15), median 8, IQR: 7.5–9.

Rationale:

A goal directed hemostatic resuscitation strategy to optimize hemostasis and correct coagulopathy is overwhelmingly recommended and supported by high quality evidence in traumatically injured adult patients.^{98, 99} We were unable to identify a pediatric-focused study that directly compared a goal directed approach to a non-goal directed approach following initial resuscitation with a MTP. However, eight studies were identified describing the use of measures of hemostasis in the resuscitation of injured children. These studies illustrate the importance of assessing abnormalities in coagulation during the trauma resuscitation and early hospital course. Additionally, the identification and management of acute traumatic coagulopathy in pediatric trauma centers is further detailed in the American College of Surgeons Committee on Trauma’s most recent iteration of the Resources for Optimal Care of the Injured Patient.¹⁰⁴ During the resuscitation process, tachycardia, hypotension, and clinical and laboratory markers of impaired end organ perfusion begin to resolve when hemodynamic stability is established. Continued administration of blood products as part of a massive transfusion protocol for hemodynamic resuscitation may be inefficient, costly, and potentially harmful. A transition to a more targeted approach for blood product administration to correct specific coagulation parameters is reasonable.

6.3: In traumatically injured children with hemorrhagic shock, adjunctive viscoelastic monitoring when available is suggested. Consensus Panel Expertise, 100% agreement (n=15), median 8, IQR: 7–9.

Rationale:

In children, studies have shown that abnormalities in VEM parameters correlate with conventional coagulation tests (CCT) abnormalities, injury severity, and mortality.^{105, 106} Studies in children have shown that compared to CCT, VEM parameters were more closely correlated with needing a life-saving intervention and mortality.^{105, 106} A retrospective, multicenter study compared outcomes in children before and after implementing a VEM-based resuscitation strategy. Using propensity score matching, the authors found that patients that received a VEM-based resuscitation strategy had more timely results, received less 24-hour red blood cell and plasma volumes, were less coagulopathic after 24 hours, and had less total hospital days. There was no difference in mortality.¹⁰⁷

Viscoelastic monitoring (VEM), including both thromboelastography (TEG) and rotational thrombelastometry (ROTEM), provide accurate and comprehensive depictions of traumatically injured adults coagulation profiles in hemorrhagic shock.¹⁰⁸ VEM provides more timely results compared to CCT.^{109, 110} Randomized prospective studies in severely injured adults receiving an MTP-based resuscitation for hemorrhagic shock showed reduced morbidity and mortality in patients that received a VEM-based resuscitation.¹¹⁰ We believe that utilization of VEM may aid in resuscitation of children in hemorrhagic shock, but as noted in recommendation 3.4, we do not believe there is sufficient data in children to utilize VEM for monitoring fibrinolysis or directing administration of TXA.

Conclusion

The Pediatric Traumatic Hemorrhagic Shock Consensus Conference aimed to provide guidance and recommendations for the resuscitation of traumatically injured children in hemorrhagic shock. Despite the lack of or low quality of the literature in the pediatric population, our expert panel has reached agreement on clinical recommendations, consensus and good practice statements to guide clinicians in care for these patients.

Supplementary Material

Appendix B

Appendix B: Good Practice Statements

NIHMS1841015-supplement-Appendix_B.docx^{(39.9KB, docx)}

Supplement

Supplemental Digital Content

PTHSCC Supplement to the Methods

Supplemental Table 1. Hierarcy of Language utilized in Statements and Recommendations

Supplemental Table 2. Pediatric Traumatic Hemorrhagic Shock Consensus Conference (PTHSCC): Search Strategies for Systematic Reviews

Supplemental Figure 1. PRISMA Diagrams for Systematic Reviews

Supplemental Table 3. Articles Included for Blood Products and Fluid Resuscitation for Hemostatic Resuscitation

Supplemental Table 4. Articles Included for Utilization of Pre-hospital Blood Products

Supplemental Table 5. Articles Included for Use of Hemostatic Adjuncts

Supplemental Table 6. Articles Included for Tourniquet Use

Supplemental Table 7. Articles Included for Pre-hospital Airway and Blood Pressure Management

Supplemental Table 8. Articles Included for Conventional Coagulation Tests or Thromboelastography-guided Resuscitation

NIHMS1841015-supplement-Supplement.docx^{(334.9KB, docx)}

Acknowledgements

We would like to acknowledge the support of the librarians at the Lister Hill Library of the Health Sciences at the University of Alabama at Birmingham: Megan Bell, Kay Smith, Jill Deaver, Geeta Malik, Rebecca Billings, and Paul Mussleman.

Funding Source:

National Institutes of Health (NIH): National Institute of Child Health & Human Development; R13HD102128 (RTR, PCS)

Footnotes

Author Disclosures: Dr. Spinella is a consultant for Secure Transfusion Services, Cerus, Haima, and Hemanext. He is the Co-Founder and Chief Medical Officer for Kalocyte. Dr. Leonard receives royalties from Up To Date^®.

Level of Evidence and Study Type: N/A

This manuscript is part of the supplement from the Pediatric Hemorrhagic Shock Consensus Conference was held in Birmingham, Alabama from April 22–24, 2022.

Social Media Handles: @russelrt132, @UABSurgery, @PhilSpinellaMD, @PittTTMRC

Hashtags: #Pediatrics, #Trauma, #Resuscitation, #Transfusion

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