Outcomes in polytrauma depend not only on prompt recognition of occult shock and early source control of bleeding but on having a standardized massive hemorrhage protocol (MHP) that enables rapid and coordinated delivery of lifesaving blood products and medications.1,2 Observational data suggest that every one-minute delay in administering the first blood product to the exsanguinating polytrauma patient is associated with a 5 percent increase in mortality.3
Explore This IssueACEP Now: Vol 40 – No 05 – May 2021
Historically, the definition of massive transfusion protocol is the administration of 10 units of red cells over 24 hours. This definition, however, is inadequate for short ED stays.4 And it’s not just transfusion. We also have to initiate a series of adjacent and often crucial actions simultaneously. MHP places the emphasis on the early, timely administration of blood products, ancillary medications such as tranexamic acid, precise clinical and laboratory monitoring and targets, temperature control, and hemorrhage control.
7 Ts of Massive Hemorrhage Protocol
The decision to activate an MHP should be guided by clinical judgment, decision tools, and response to early management. There is no one clinical or laboratory finding that accurately predicts the need to activate an MHP. Nonetheless, there are three time periods during which activation of an MHP should be considered: prehospital, ED arrival, and intra-resuscitation. During the prehospital period, a concerning mechanism of injury such as a fall from three stories or a shock index (heart rate/systolic blood pressure) ≥1 should trigger the consideration for an MHP activation.5
When the patient arrives to the trauma bay, clinical judgment, clinical decision tools, and pitfall conditions should be considered. A Revised Assessment of Bleeding and Transfusion (RABT) score ≥2 has been shown to be more accurate than the Airway, Breathing, and Circulation (ABC) score in predicting the need for massive transfusion.6 RABT assigns one point each for shock index >1, pelvic fracture, positive Focused Assessment with Sonography for Trauma (FAST), and penetrating injury. Pitfall conditions that may lower the threshold for activating an MHP include those patients who are elderly, those taking anticoagulant medications or dual antiplatelet therapy, and those taking medications that may blunt hemodynamic response to hemorrhage such as a beta blockers.
The third time period to consider activation of an MHP is during resuscitation. Resuscitation intensity has been suggested as a trigger; specifically, if there has been a requirement of three units of any combination of crystalloids or blood products to maintain adequate tissue perfusion, we might call this an “intense” resuscitation.7 I recommend a 2:1:1 ratio of red cells to plasma to platelets. This is based on my interpretation of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial, which found no significant mortality difference at one or 30 days between those patients who received a 1:1:1 ratio versus a 2:1:1 ratio.8 The 2:1:1 ratio may allow for faster administration of blood products since plasma takes time to thaw and can therefore be a rate-limiting bottleneck. Hence, our goal should be to have four units of uncrossmatched red cells at the bedside in under 10 minutes, with a rapid transfuser administering the blood product soon thereafter. If more blood product is required to maintain adequate tissue perfusion, then four units of plasma and four units of red cells should be transfused simultaneously thereafter. Benefits of this strategy are twofold: Administration of red cells is not delayed by plasma preparation (ie, labeling and thawing), and some patients will stabilize with red cells only.
While this strategy is familiar to North American trauma centers, some European centers favor a fibrinogen and prothrombin complex concentrates (PCCs)–first strategy. Small randomized trials suggest that using fibrinogen concentrate or cryoprecipitate with or without PCCs is at least as effective as the North American red cell/plasma strategy at 1:1, though larger trials are required to further corroborate these findings. 9 The benefits of the concentrate strategy are that blood products can be kept at room temperature in the trauma bay for rapid access, a blood group is not necessary, the need for AB plasma (often in short supply) is avoided, they are pathogen-reduced small volumes injected over minutes, and they do not cause transfusion-related acute lung injury—a not uncommon complication of red cell transfusions. A fibrinogen and PCCs-first strategy should be considered in rural hospital settings where blood products may not be immediately available.
Preparing yourself, your team, and your equipment is essential for optimizing care. Psychological preparation affects both individual and team performance.10 Visualization of complex tasks, deep breathing exercises, and positive self-talk can help focus.10 To ensure rapid delivery of blood products and bleeding source control, early notification and preparation of the extended team—including the ED team, laboratory team, blood bank, and surgical team—are recommended. Time permitting, briefing the ED team is important, based on the limited data gathered from paramedics, and should include prioritizing objectives and assigning roles with each team player and ensuring specific equipment is in place and ready. Adapting a shared mental model may improve team performance.10
A standardized order set for laboratory tests can help reduce cognitive burden and more rapidly identify potential coagulopathy and metabolic dysfunction caused by massive hemorrhage.11 Without a standardized order set, the most common laboratory tests that are omitted in the emergency department are calcium and fibrinogen. Calcium plays an important role in regulating coagulation and hemostasis. The citrate preservative in blood products binds to serum calcium, making it inactive. It is therefore important to monitor serum calcium and to consider administering supplemental calcium every three to four blood products that are administered. Fibrinogen is consumed in coagulopathies of trauma and diluted by the administration of blood products. It requires careful monitoring and replacement with cryoprecipitate or fibrinogen concentrate. Pregnant and postpartum patients with active hemorrhage tend to have lower fibrinogen levels compared to other patients, and they carry an increased risk for disseminated intravascular coagulation.12 It is thus imperative to have a low threshold to administer fibrinogen in the pregnant or postpartum polytrauma patient with massive hemorrhage.
To assess the trajectory of the trauma resuscitation, in addition to hemoglobin, fibrinogen, and lactate, international normalized ratio (INR) should be monitored. Elevated INR has been shown to predict poor outcomes in trauma patients; correcting it with fresh frozen plasma (FFP), with or without PCCs, is advised.13 If the patient with imminent life-threatening bleeding is known to be taking warfarin and an MHP has been activated, both FFP at a minimum ratio of 1:2 and 2,000 IU prothrombin concentrates, plus 10 mg of vitamin K, should be administered. It is not necessary to wait for the INR result before administering PCCs in this context.
4. Tranexamic Acid
Despite recent literature suggesting no benefit and potential harms in patients with massive gastrointestinal bleeding, in many centers, tranexamic acid (TXA) continues to be part of the standard order set for polytrauma patients based on the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage 2 (CRASH-2) trial.14,15 TXA administration is recommended for all trauma patients suspected of life-threatening hemorrhage within three hours of the time of injury who are deemed candidates for massive transfusion as well as for patients with initial systolic blood pressure <90 or heart rate (HR) >110. Observational data suggest that every 15-minute delay decreases its mortality benefit by 10 percent.16 An important exception for the administration of TXA in trauma patients is for isolated head injury. The CRASH-3 trial did not show a clinically significant benefit for early administration of TXA in these patients.17 For patients seen at nontrauma centers being prepared for transfer to one, if TXA is indicated, it is imperative that it be administered prior to transfer. The dose of TXA in the CRASH-2 trial was 1 g bolus followed by 1 g infusion over eight hours. However, subsequent observational data in trauma patients suggest that as much as half the time, the infusion of TXA after the initial 1 g bolus is not given at all.18 This may be because the infusion is associated with logistical problems of requiring a dedicated IV. This has led some experts to administer a one-time 2 g IV dose up-front to ensure all patients receive an adequate dose of TXA.
Hypothermia has been shown to increase mortality via worsening coagulopathy in trauma patients.19 It can result from prehospital environmental conditions, the trauma itself, or administration of blood products. It is important to monitor the patient’s rectal temperature during the initial ED assessment and at least every hour thereafter, depending on whether the patient presented to the ED hypothermic. To prevent hypothermia, remove wet clothing, place warm blankets, and administer warmed IV products.
Clinical, hematologic, and metabolic resuscitation targets are used to monitor patient tissue perfusion and response to resuscitation and for prognostication. Clinical targets to consider include HR <100, mean arterial pressure >55–70 (depending on baseline blood pressure), Glasgow Coma Scale >15 (if no head injury or intoxication), urine output >30 mL/hr, and normal inferior vena cava diameter/collapsibility on point-of-care ultrasound. Hematologic targets include serum hemoglobin >8 mmol/L, platelets >50 x 109/L (>100 in head injured patients), INR >1.8, and fibrinogen 1.5–2 g/L. Metabolic targets include pH >7.3, lactate <4 mmol/L, and serum calcium >1.15 mmol/L.2
The general requirements for termination of an MHP include reaching the clinical, hematologic, and metabolic targets described above. However, the decision to cease an MHP is often more nuanced, usually requiring collaboration between the emergency department and inpatient teams. A common pitfall is terminating an MHP at the first sign of hemodynamic stability, only to be hit with a second wave of hemorrhage and instability during transfer to the operating room. Peri-trauma vasoplegia may occur despite appropriate resuscitation.
Whether you work in a rural setting or a state-of-the-art trauma center, a standardized, protocolized approach using the “7 Ts” to massive hemorrhage in trauma patients will help your workflow and your patients.
A special thanks to Dr. Jeannie Callum, Dr. Barabara Haas, and Dr. Andrew Petrosoniak, whose expertise on an EM Cases podcast inspired this column.