The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient

Abstract

The recognition and management of life-threatening hemorrhage in the polytrauma patient poses several challenges to prehospital rescue personnel and hospital providers. First, identification of acute blood loss and the magnitude of lost volume after torso injury may not be readily apparent in the field. Because of the expression of highly effective physiological mechanisms that compensate for a sudden decrease in circulatory volume, a polytrauma patient with a significant blood loss may appear normal during examination by first responders. Consequently, for every polytrauma victim with a significant mechanism of injury we assume substantial blood loss has occurred and life-threatening hemorrhage is progressing until we can prove the contrary. Second, a decision to begin damage control resuscitation (DCR), a costly, highly complex, and potentially dangerous intervention must often be reached with little time and without sufficient clinical information about the intended recipient. Whether to begin DCR in the prehospital phase remains controversial. Furthermore, DCR executed imperfectly has the potential to worsen serious derangements including acidosis, coagulopathy, and profound homeostatic imbalances that DCR is designed to correct. Additionally, transfusion of large amounts of homologous blood during DCR potentially disrupts immune and inflammatory systems, which may induce severe systemic autoinflammatory disease in the aftermath of DCR. Third, controversy remains over the composition of components that are transfused during DCR. For practical reasons, unmatched liquid plasma or freeze-dried plasma is transfused now more commonly than ABO-matched fresh frozen plasma. Low-titer type O whole blood may prove safer than red cell components, although maintaining an inventory of whole blood for possible massive transfusion during DCR creates significant challenges for blood banks. Lastly, as the primary principle of management of life-threatening hemorrhage is surgical or angiographic control of bleeding, DCR must not eclipse these definitive interventions.

Keywords: coagulopathy; endotheliopathy; hemorrhage; macrocirculation; microcirculation; oxygen transport; polytrauma; resuscitation; shock.

Figure 1

(A) OHD curve which relates the saturation of Hgb (y-axis) to the degree of partial pressure of oxygen to which Hgb is exposed (x-axis). The pO₂ that saturates ½ of Hgb is referred to as p50, which in this example p50 = 27 mmHg. The p50 is the conventional measure of affinity of Hgb for oxygen. The lower the p50 the higher the affinity of Hgb for oxygen. The ‘steep’ portion of the oxyHgb dissociation curve is in the range of pO₂ that exists in systemic capillaries (thus a small decrease in systemic capillary pO₂ can result in the release of large amounts of oxygen for diffusion to, and uptake by cells). As shown in the figure, several factors increase the affinity of Hgb for oxygen (leftward shift; ↓p50) or decrease affinity (rightward shift; ↑p50). Biochemically, H+ is a heterotropic allosteric inhibitor of Hgb, whereas O₂ is a homeotropic allosteric activator of Hgb. (B) Hypothermia and acidosis have opposing effects on p50. Lower temperature shifts the curve to the left increasing Hgb affinity for oxygen and decreasing offloading in capillaries; low pH (increase in H+) decreases the affinity of Hgb for oxygen (Bohr effect) increasing oxygen availability to reverse anaerobic metabolism. A trauma patient may be, and often is hypothermic and acidotic (and coagulopathic). Whether there is a significant change in p50 can be calculated using the Hill–Langmuir equation. (C): Hypothetical oxygen transport variables of a normal subject (Temp = 37 °C; p50 = 25 mmHg) and a subject with hypothermia (Temp = 31 °C; p50 = 20 mmHg), before and after compensation. The p50 at 31 °C and pH = 7.4 is calculated using the Hill–Langmuir equation. A venous blood gas is obtained through a Swan Catheter introducer (7.5Fr) with the tip in the superior vena cava reveals in the hypothermic subject, central venous oxygen saturation (ScvO₂) = 85%. This reflects the fact that hypothermia increases the affinity of Hgb for oxygen, shifting the Hgb dissociation curve to the left. A ScvO₂ of 85% would imply only 15% of the delivered 1000 mL of oxygen (DO₂) prior to compensation is being offloaded, which is approximately 150 mL/min, well below VO₂ (250 mL/min). The hypothermic patient can compensate by increasing cardiac output and hence DO₂. Assume that stroke volume is unchanged (although a well-known consequence of tachycardia is a reduction in stroke volume), and cardiac output increases by an increase in heart rate (HR) from 72 beats/min to 120 beats/min (a 40% increase in HR causing a substantial increase in myocardial oxygen demand).

Figure 2

DO_{2 CRIT} defines shock. As DO₂ (solid black line) decreases secondary to a fall in cardiac output, drop in Hgb concentration, or both, O₂ER (solid grey line) increases to maintain VO₂ constant until extraction is maximized. At this point, designated as DO_{2 CRIT} (also referred to as the anaerobic threshold), VO₂ begins to decrease with further decreases in DO₂. When DO₂ > DO_{2 CRIT} t, VO₂ is flow-independent; when DO₂ < DO_{2 CRIT}, VO₂ becomes flow-dependent. In addition, DO_{2 CRIT} is associated with the onset of lactate formation and accumulation. Thus, shock can be defined conceptually as the presence of DO₂ less than DO_{2 CRIT}, producing a reduction in VO₂. Normal DO₂ = 800 mL O₂/min/m²; normal VO₂ = 200 mL O₂/min/m²; normal O₂ER = 25%.

Figure 3

Pathways of plasminogen activation and inhibition. Plasminogen is synthesized by and released from the liver. To be activated to plasmin, plasminogen initially binds to lysine residues exposed on fibrin. The generation of plasmin from its precursor, plasminogen is achieved by the plasminogen activators, tissue-type type plasminogen activator (tPA), and urokinase (not depicted). Protien C, once activated by thrombin bound to thrombomodulin blocks PAI-1, the major inhibitor of tPA; therefore thrombin, through activated protein C, can promote fibrinolysis. However, thrombin-thrombimodulin interactions can also inhibit fibrinolysis through activation of TAFI (thrombin-activatable fibrinolysis inhibitor). Plasmin once formed can also cleave plasma prekallikrein (Fletcher factor) and Hageman factor (FXII) and in turn plasminogen can be activated to plasmin by these proteases. Furthermore, plasmin, can activate the complement factors, C5 and C3, while on the other hand, it can itself be inhibited by the C1-inhibitor, thereby providing a natural means to regulate this process. Excessive plasmin formation can result in hyperfibrinolysis, which increases the risk of bleeding. Tranexamic acid (TXA) blocks lysine-dependent interactions and therefore inhibits binding of plasminogen to and transfusion requirements. Plasminogen receptors located on the surface of immune cells also contain C-terminal lysine the surface of fibrin and misfolded proteins. Plasmin also activates other substrates with pro-inflammatory potential including TGF-β, a neurotrophic agent brain-derived neurotropic factor, and other proteases like the matrix metalloproteinases.

Figure 4

Thromboelastography (TEG^®). (A) Schematic presentation of different viscoelastic tracings reflecting states of the coagulation system compared with normal. (B) Basic viscoelastic tracing with measured parameters and limits of normal for thromboelastography, correlated with different elements of the coagulation system (R = reaction time, K = clot formation time, angle, MA = maximum amplitude, Ly30 = percent clot lysis 30 m after MA). Viscoelastic k-time and angle correlate to some degree with fibrinogen concentration. However, the agreement between these parameters and fibrinogen levels determined by standard von Clauss assay is not sufficiently strong to be useful clinically. To overcome this limitation with TEG, the specific contributions of fibrinogen and platelets to clot strength can be determined with additional reagents (TEG; Functional Fibrinogen [Haemonetics Corp, Niles, IL, USA]). Using TEG, additional measures of clot strength can be computed. Coagulation index (CI; black arrow) is derived from R, k-time, angle, and MA, with a CI >+3.0 suggesting a hypercoagulable state and CI <−3.0 suggesting coagulopathy. The shear elastic module strength, designated G, is a computer-generated quantity that reflects an integrated measure of clot strength. Conceptually, G is considered the most informative parameter of clot strength because it reflects the contributions of the enzymatic and platelet components of hemostasis. Abbreviations: rTEG, rapid thromboelastography; DIC, disseminated intravascular coagulation; EPL, estimated percent lysis; FFP, fresh frozen plasma; Cryo, cryoprecipitate; Plts, platelets; TXA, tranexamic acid.