There is some data to support the use of small volumes of crystalloid such that the deleterious effects of volume overload are avoided while maintaining both macro- and microperfusion in patients who present with class I/II hemorrhage. However, large-volume crystalloid resuscitation in the face of exsanguinating hemorrhage has been shown macroscopically to cause edema of the gut, myocardium, and skeletal muscles, compartment syndrome, and acute respiratory distress syndrome and microscopically to induce tissue hypoxia and free-radical injury leading to derangements of cellular, metabolic, and immune functions. Meanwhile, the traditional approach to blood component transfusion for class III/IV hemorrhagic shock wherein one unit of fresh frozen plasma (FFP) was transfused for every six units of packed red blood cells (PRBCs) and one unit of platelets transfused for every ten units of PRBCs has been shown to result in acidosis, hypothermia, and coagulopathy. When this so-called lethal triad occurs, diffuse hemorrhage continues despite operative control at the injury site(s) and often results in death. Therefore, large-volume crystalloid infusion has largely been replaced by blood product transfusion in fixed ratios of red blood cells/plasma/platelets approaching 1:1:1 or 1:1:2 as evidenced by the Pragmatic Randomized Optimal Plasma and Platelet Ratios (PROPPR) trial which did not show 24 h or 30-day mortality differences between these ratios. Even when ratios are maintained, increasing volume of crystalloid is a predictor of mortality. Finally, the mortality benefits of an established protocol with a balanced ratio of blood products with minimization of crystalloid infusion, even if not 1:1:1, have also been shown as such a protocol mitigates delays in access to blood products and ensures correct ratios at whatever level they have been agreed upon.

Colloids (typically 5 % albumin or 6 % hetastarch) and hypertonic fluids (7.5 % saline with or without 6 % dextran) have been sought as alternatives to crystalloids for their higher oncotic pressure and hypertonicity, but numerous studies failed to show any mortality advantage of these fluids. Similarly, given that blood component therapy suffers from lack of donors, storage issues, and risks of transfusion, various hemoglobin solutions that would provide the benefits of blood transfusion, in particular with regard to oxygen-carrying capacity, without the risks and with longer shelf lives were created and tested. Unfortunately, none have shown the mortality benefit hoped for, and some have been associated with significant adverse effects including higher mortality.

If an injured patient has evidence of intact perfusion as measured by normal blood pressure or evidence of end-organ perfusion (intact mental status, palpable radial pulse), he/she does not need to be aggressively resuscitated or transfused. In recent years, a number of approaches to determining need for massive transfusion, retrospectively defined by most as the need for ≥10 unit PRBCs in the first 24 h after injury, have been tested.

The Trauma-Associated Severe Hemorrhage (TASH) and the Assessment of Blood Consumption (ABC) scores are the most widely used. However, the former was derived from a cohort of blunt trauma patients and consists of a relatively complicated calculation utilizing seven weighted variables (systolic blood pressure, sex, hemoglobin, focused assessment for the sonography of trauma (FAST), heart rate, base excess (BE), and extremity or pelvic fractures) to predict need for massive transfusion. The possible range of scores is between 0 and 28, where each point corresponds to increased risk, and 100 % of patients with a score ≥27 require massive transfusion. Conversely, ABC accounts for mechanism of injury (penetrating vs. blunt) and is simpler to derive. It also includes systolic blood pressure ≤ 90 mmHg on emergency room (ER) arrival, heart rate ≥120 bpm on ER arrival, and positive FAST, where each parameter equals 1 point and 85 % of patients with a score of ≥2 will require massive transfusion. Application of such scores to MTP practices will streamline resource utilization and clinical decision-making at the bedside when patients are not in obvious class III or IV hemorrhagic shock.

Trauma-induced coagulopathy (TIC) occurs when the body’s hemostatic mechanisms at the cellular level become deranged in the face of massive exsanguination. Thrombus can no longer form and uncontrolled hemorrhage, not just from the site(s) of injury, occurs. TIC occurs in 10–34 % of injured patients and has been associated with increased mortality. While early research suggested that high-volume crystalloid infusion and wide blood product ratios were causative factors, it appears that these approaches to resuscitation were actually exacerbating, rather than inducing, post-injury coagulopathy which has been attributed to increased activation of activated protein C, hyperfibrinolysis, and platelet dysfunction due to injury itself. Therefore, in addition to limiting (in the case of crystalloids) or modulating (in the case of blood product ratios) these exacerbating factors as detailed above, efforts to identify and ameliorate TIC have also emerged.

Traditional approaches to measuring coagulopathy are either impractical (e.g., bleeding time is difficult to measure in a patient undergoing interventions in the trauma bay for hemodynamic compromise; serum laboratory data even if stat can take up to 2 h to return) or not reliable (e.g., platelet count does not reflect platelet function; fibrinogen, prothrombin time, and partial thromboplastin time each only reflect one aspect of the coagulation cascade) for patients presenting with hemorrhagic shock; therefore, point-of-care testing of whole-blood viscoelasticity has been developed. The two most widely studied in trauma are thromboelastography (TEG) and rotational thromboelastometry (ROTEM). TEG and ROTEM will show which part(s) of the coagulation cascade is impaired. While the validity of these measures has not definitely been proven in a prospective manner, TEG and ROTEM results allow assessment of adequacy of clotting factors, platelet function, and fibrinolysis. A detailed discussion of the interpretation of TEG and ROTEM is beyond the scope of this chapter; however, Fig. 7.1 provides a schematic of how a TEG or ROTEM result might be interpreted to guide resuscitation. Importantly, normal TEG or ROTEM does not rule out bleeding. Rather, it confirms normal coagulation cascade. A number of centers have reported using TEG or ROTEM in the trauma bay to guide resuscitation with specific blood components, cryoprecipitate, concentrated clotting factors, and pharmacologic adjuncts rather than blindly following a prescribed ratio of blood components for patients in hemorrhagic shock. Based on current evidence, these point-of-care tests should be considered in conjunction with MTPs.

Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine that inhibits fibrinolysis. It is indicated for primary hyperfibrinolysis. The effectiveness of TXA in the face of “significant hemorrhage” was measured in the large clinical trial Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2). The study found that administering 1 gm of TXA within 3 h of onset of bleeding as a bolus over 10 min and then providing a maintenance dose of 1gm infused over the next 8 h reduced all-cause mortality from 16 to 14.5 % (RR 0.91, 95 % CI 0.85–0.97) without increasing thrombotic events. Since this study was published, administering TXA in concert with an MTP has been widely adopted. These reports support including TXA in modern-day MTPs for patients who present within 3 h of onset of bleeding.

Pharmacologic coagulopathy, in particular in the era of novel oral anticoagulants, is also a concern in the resuscitation approach after penetrating trauma. Pharmacologic coagulopathy should be considered based on patient history, if known; and, in certain cases, TEG or ROTEM might provide a clue regarding which class of anticoagulant a patient is on if the history is unknown (see Fig. 7.1). Reversal strategies for various anticoagulants differ and should be immediately implemented in an exsanguinating trauma patient. While a detailed discussion of reversal of pharmacologic coagulopathy is beyond the scope of this chapter, common recommendations for oral anticoagulants are listed in Table 7.2. As with MTPs, protocolization of reversal of common anticoagulants may expedite hemorrhage control.