MECHANICAL HEMORRHAGE CONTROL
In addition to blood replacement, DCR strategies also focus on limiting blood loss with hemorrhage control devices and adjunctive pharmaceutical therapies. Availability and usefulness of interventions are determined by the type of injury and location of bleeding. Effective tourniquets (e.g., Combat Application Tourniquet, Special Operations Forces Tactical Tourniquet) have been developed for extremity injury and may be responsible for saving more wounded service members in Iraq and Afghanistan than any other single medical intervention. Junctional (axillary, neck, and groin) hemorrhage, previously a nearly intractable problem, can now be treated with approved junctional tourniquets (e.g., Combat Ready Clamp, SAM® Junctional Tourniquet, Junctional Emergency Treatment Tool) and the XSTAT™ device, which injects absorbent sponges into deep wounds to tamponade bleeding.58-60 Superficial wounds are amenable to novel and effective hemostatic dressings (e.g., Combat Gauze or Celox/Celox Rapid gauze).
Truncal internal hemorrhage is non-compressible and is the subject of intensive research. Resuscitative Endovascular Occlusion of the Aorta (REBOA) has emerged as a technique for truncal hemorrhage control. The newest device available does not require fluoroscopic guidance and has become widely available; in expert hands on teams with appropriate training, REBOA may improve survival from non-compressible truncal hemorrhage. There is no 24-hour outcome data on the use of REBOA in the combat environment. Teams that use this technique should be submitting clinical data to the JTS in order to better understand this capability and how it effects outcomes from hemorrhage. The ideal application of REBOA in the combat environment is evolving, but the technique, when used appropriately, has the potential to significantly improve outcomes from non-compressible truncal hemorrhage. Currently, REBOA use is supported for austere surgical teams, and teams that have an immediate surgical capability are using REBOA. See the JTS REBOA for Hemorrhagic Shock CPG. 61-67
PHARMACOLOGIC ADJUNCTS
Hemostatic pharmaceutical adjuncts to limit blood loss are another subject of considerable investigation.
Tranexamic acid (TXA) is the only therapy in this class that has been found to reduce mortality in a large Randomized Controlled Trial (RCT). Strong evidence demonstrates a significant improvement in survival following the early use of TXA, but only when given within 3 hours of injury.68,69 Significant trauma-- in particular, penetrating trauma with hemorrhage--has been associated with coagulopathy, in part secondary to the activation of fibrinolysis.1,70 Such hyperfibrinolysis occurs in the most severely injured patients (approximately 4% of trauma patients in major civilian U.S. trauma centers) and portends poor outcomes.9,71 Anti-fibrinolytic agents, including TXA, have been used to decrease bleeding and to reduce the need for blood transfusions in coronary artery bypass grafting, orthotopic liver transplantation, hip and knee arthroplasty, obstetrics, and other surgical settings. The safety and efficacy of using TXA to treat trauma patients was evaluated in a large randomized, placebo-controlled clinical trial The Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage (CRASH-2).72 In this trial, 20,211 adult trauma patients in 274 hospitals in 40 countries with, or at risk of, significant bleeding (HR>110, SBP<90, clinical judgment) were randomized to either TXA or placebo. The authors reported that TXA use resulted in a statistically significant reduction in the relative risk of all-cause mortality of 9% (14.5% vs.
%, RR 0.91, CI 0.85-0.97; p = 0.0035). It was in this group of most severely injured patients that use of TXA was associated with the greatest reduction in risk of death.
A registry-based study of combat-injured troops receiving blood in Afghanistan (January 2009 - December 2010) demonstrated a decreased mortality with TXA use in this population. The TXA group was more severely injured (ISS: 25.2±16.6 vs. 22.5±18.5; p<0.001), required more blood (11.8±12.1 vs. 9.8±13.1 pRBC units; p<0.001), had a lower Glasgow Coma Score (7.3±5.5 vs. 10.5±5.5; p<0.001) and initial systolic blood pressure (112±29.1 vs. 122.5±30.3 mmHg), but also had a lower unadjusted mortality than the no-TXA group (17.4% vs. 23.9%; p=0.028). In the massive transfusion cohort (N=321; 24-hour transfusion: 21.9±14.7 pRBC; 19.1±13.3 FFP and 3.5±3.2 apheresis platelet units), mortality was also lower in the TXA group compared to the no-TXA group (14.4% vs. 28.1%; p=0.004). In a multivariate regression model, TXA use in the massive transfusion cohort was independently associated with survival (odds ratio: 7.28; 95% confidence interval: 3.02-17.32). A subsequent larger retrospective analysis of TXA use outcomes in military casualties documented an increased rate of venous thromboembolism in patients receiving TXA.73 Estimates of TXA effects on mortality suggested that an adequately powered study would likely observe an effect size in line with CRASH-2 findings.
This survival benefit associated with TXA supports its use in conjunction with damage control resuscitation following combat injury. This association is most prominent in those requiring massive transfusion.14,74 In casualties at high risk of hemorrhagic shock, TXA reduces mortality IF GIVEN WITHIN THREE (3) HOURS of injury, optimal use of TXA requires that it be given as soon as possible when indicated rather than suggesting that TXA administration any time within 3 hours after injury is acceptable.75,76 TXA given empirically greater than 3 hours post-injury increases the risk of mortality. For eligible casualties, 2 grams of TXA should be administered IV or IO. (See next section Recognition of Patients Requiring DCR to determine eligible casualties.) TXA is ideally administered in 100 ml of normal saline over 10 minutes, but faster administration in more concentrated form can be considered. Administration of undiluted TXA by slow IV push (given over 10 minutes) is acceptable if supplies or tactical situation prevents 100mL IV infusion.77 It should be noted that rapid infusion of TXA has been infrequently associated with transient hypotension. Although Lactated Ringer’s (LR) solution is compatible with TXA, its use should be avoided in this setting since the mixing of calcium containing LR with blood products in chaotic resuscitation settings may cause clotting of blood products and thromboembolic phenomena. Normal saline and PlasmaLyte A are the only crystalloid solutions compatible with blood products
CAUTION: Do not mix medications and blood products in the same IV line. Use a separate line or flush well between giving medications and blood products.
Hypocalcemia is a problem in most actively bleeding trauma patients on presentation, and administration of even one unit of citrated blood product can further lower ionized calcium to levels approaching critical values (<0.9mmol/l). One gram of calcium IV/IO should be given to patients in hemorrhagic shock during or immediately after transfusion of the first unit of blood product and with ongoing resuscitation after every 4 units of blood products. At a minimum, one gram of calcium should be administered after no more than 4 units of blood product have been infused to avoid citrate toxicity. Ideally, ionized calcium should be monitored and calcium should be given for ionized calcium less than 1.2mmol/L. This should be done at the first level of care capable of monitoring these patients, typically a Role 2 equivalent or above. Appropriate calcium solutions should otherwise be administered per protocol for signs and symptoms of hypocalcemia (e.g., prolonged QTc, ventricular arrhythmias, decreased cardiac output/cardiovascular collapse, coagulopathy, tetany, laryngospasm, seizures, and paresthesia)
CAUTION: Calcium gluconate is safer for peripheral use. Calcium chloride may cause severe skin necrosis if extravasation occurs through a partially dislodged IV or IO catheter. The risk of bone necrosis with IO injection of calcium chloride is not known. When using peripheral IV or IO access, use extreme caution to ensure the device is in good intravascular position and no extravasation occurs.
Note that hypomagnesemia is also common in trauma patients and is worsened by citrate- containing blood products. Hypomagnesemia may contribute to increased cardiac irritability and risk of fatal arrhythmias. Consideration should be given to replacing magnesium in the setting of severe hypocalcemia and massive transfusion.4,78-80
The use of rFVIIa is no longer recommended in most trauma patients since it has not been shown to reduce mortality and may increase risk of adverse events.81-85