Severe Traumaand Hemorrhagic Shock

Rainer Lenhardt, M.D., MBAAssociate Professor

Vice-Chair for Clinical AffairsDirector, NeuroSciences/Anesthesia Critical Care Unit

Department of AnesthesiologyUniversity of Louisville

Louisville, Kentucky

LESSON OBJECTIVES 5.Upon completion of this lesson, the reader 6.should be able to:1. Describe the classification of hemorrhage 7.

in trauma patients.2. Define massive transfusion in trauma 8.

resuscitation.3. Describe common patterns of clinical 9.

presentations of trauma hemorrhage.4. Identify hypothermia as a major com- 10.

ponent of ongoing hemorrhage in trauma.

Explain the lethal triad in severe trauma.Describe the coagulopathy of acutetrauma shock.Discuss the impact on acidosis with mas-sive bleeding.Explain damage control surgery anddamage control resuscitation.List all relevant blood products used inmassive transfusion.Discuss the necessity to implement a mas-sive transfusion protocol.

Current Reviews for Nurse Anesthetists designates this lessonfor 1 CE contact hour in Clinical pharmacology/therapeutics.

IntroductionSevere trauma is the leading cause of mor-

tality in patients under the age of 45. Two rea-sons account for the majority of these deaths:traumatic brain injury and hemorrhagic shock.Mortality can occur early, within 24 hours aftersevere trauma, or late, some days after the trau-matic event. The most common cause of earlymortality is exsanguination and the subsequenthemorrhagic shock; the mortality of patients whodevelop hemorrhagic shock is about 50% in theprehospital phase and nearly 80% in the operatingroom. In contrast, after the first 24 hours, trau-matic brain injury replaces hemorrhage as the

leading cause of trauma-related mortality. Earlyhypotension, the amount of hemorrhage, multipleorgan failure and infection are all predictors oflate mortality (Table 1). Early hypotension isdefined as a systolic blood pressure less than 90mmHg in the prehospital phase or in the emer-gency room. The amount of blood loss is the vol-ume of hemorrhage as measured by blood pres-sure and the number of blood units replaced.Multiple organ failure is a direct consequence ofprotracted organ hypoperfusion. Infection mostlypresents as sepsis or severe pneumonia withdevelopment of acute respiratory distress syn-drome (ARDS).

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Early resuscitation of severely traumatizedpatients is of paramount importance to assure thebest possible outcome. Resuscitation comprisesdamage control surgery and damage controlresuscitation. The trauma surgeon performsdamage control surgery and focuses on surgicalhemostasis. The surgeon's efforts are supportedby damage control resuscitation, meaning therestoration of circulating intravascular volume.This includes the administration of blood productsand the treatment of coagulopathy, acidosis, andhypothermia. In most cases, massive transfusionis necessary and a massive infusion protocol mustbe initiated to treat the impending hemorrhagicshock.

Classification of HemorrhageAccording to the American College of Surgeons,

hemorrhage is broken down into the following fourclasses (Table 2):• Class I hemorrhage involves loss of up to 15%

of the circulating blood volume. There is typ-ically no change in vital signs and fluid resus-citation is not usually necessary.

• Class II hemorrhage involves loss of 15-30%of the circulating blood volume. A patient isoften tachycardic with a narrowing of the pulsepressure. Peripheral vasoconstriction ensues.Volume resuscitation with crystalloids is re-quired. Blood transfusion is not typically re-quired.

• Class III hemorrhage involves loss of 30-40%of the circulating blood volume. The patient'sblood pressure drops, the heart rate increases,peripheral perfusion—such as capillary refill—worsens, and the mental status worsens. Fluidresuscitation with crystalloid and blood trans-fusion are usually necessary.

• Class IV hemorrhage involves loss of > 40% ofthe circulating blood volume. The limit of thebody's compensation is reached making bloodtransfusion mandatory.

Table 1Markers for Late Mortality

Early hypotension defined assystolic blood pressure < 90 mmHgVolume of hemorrhage as measuredby blood pressure and the numberof blood units replacedMultiple organ failure (MOF)Infections such as pneumonia andsepsis

Table 2Classification of Hemorrhage

Class I hemorrhage blood loss < 15%

Class II hemorrhage blood loss 15-30%

Class III hemorrhage blood loss 30-40%

Class IV hemorrhage blood loss > 40%•* blood transfusion mandatory

Patients with class IV hemorrhage are subject tomassive transfusion.

Massive transfusion has been defined as the lossof 50% of the circulating blood volume in 3 hours orless. Another definition is the administration ofmore than 10 units of packed red blood cells (PRBC)within 24 hours. For example, a male patient witha hematocrit of 40% has a red blood cell (RBC)volume of 2000 ml, which is the equivalent of 10units of PRBC.

Early mortality is mainly caused by trau-matic hemorrhage and traumatic braininjury or a combination of both.

Clinical Presentationof Trauma Hemorrhage

Most trauma patients present to the emergencyroom with a mild or moderate trauma score cor-responding to class I-III hemorrhage. These patientsare usually in a hypercoagulable state. However, asmall portion of patients suffer severe trauma andrequire massive blood transfusion (Class IV hem-orrhage). This small segment of trauma patientsaccounts for 75% of the overall blood utilization andis typically hypocoagulable.

Evidence suggests that patients with severetrauma and massive hemorrhage have some coag-ulopathy when admitted to the hospital. This coag-ulopathy occurs very early in about 25^ of admittedpatients. This condition is referred to as acutecoagulopathy of trauma shock (ACoTS). ACoTS isnot a simple dilution coagulopathy that occurs ininjured patients, but a complex problem with mul-tiple factors. The key initiators to the process ofACoTS are shock and hypoperfusion. Besides earlycoagulopathy, shock causes acidosis and hypo-thermia. The combination of coagulopathy,acidosis, and hypothermia is called the lethaltriad as illustrated in Figure 1. The lethal triadis associated with a significant increase of mor-tality.

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CoagulopathyAcute coagulopathy of trauma shock is charac-

terized by activation of protein C and hyperfibrin-olysis. As hemorrhagic shock advances, excessiveactivation of coagulation ensues. This results in thedevelopment of disseminated intravascular coag-ulation (DIG) and the exaggerated generation ofthrombin and fibrin with consumption of plateletsand coagulation factors.

In addition to the consumption of coagulationfactors and platelets, coagulation factors are lostdirectly through hemorrhage. Frequently, earlyblood loss is replaced by crystalloids, colloids and(RBCs). This replacement promotes dilution ofcoagulation factors thereby further reducing theability to form blood clots.

Even if fresh frozen plasma (FFP) has beenordered early in the treatment of hemorrhage, ittakes about 20-30 minutes to thaw FFP before itcan be infused. This delay may result in additionalreduction in coagulation factors.

AcidosisHemorrhagic shock leads to hypoperfusion of

body tissues, causing a switch from aerobic to an-aerobic cellular metabolism because of the lack ofoxygen transfer to the tissues. Anaerobic metabo-lism causes accumulation of lactic acid. This lacticacidosis induces a drop in pH and increases negativebase excess values. Depending on the degree of baseexcess, acidosis is classified as mild, moderate, orsevere acidosis (Table 3).

Acidosis impairs essential parts of thehemostatic proce - - . :sis inhibits the activityof coagulation enzyme complexes on lipid surfaces.When pH is reduced from 7.4 to 7.0, the activity levelof Factor Vila is reduced by 9CKt, factor Vila/tissuefactor (TF) complex is reduced by 55%, and pro-

Figure 1. The Lethal Triad

Table 3Classification of Acidosis

as Defined by Base Deficit Values

Mild: -3to-5mEq/LModerate: -6 to -9 mEq/LSevere: less than -10 mEq/L

thrombin activation by factor Xa/factor Va complexis reduced by 70%. Acidemia also leads to increaseddegradation of fibrinogen.

Increased levels of plasminogen activator caus-ing hyperfibrinolysis further enhance dysregulationof coagulation. Thus, blood clots once formed may bedissolved again and contribute to ongoing bleeding.Furthermore, acidosis contributes to a change in theshape of platelets. Thrombocytes become sphericaland lose their pseudopodia. This change causes animpaired capacity of platelets to adhere to vascularinjuries.

Overall, acidosis causes an impairment of throm-bin formation, which can be seen as one of the majorreasons for the ongoing coagulopathic bleeding. It isimportant to note that correction of acidemia per sedoes not reverse the coagulopathy.

Markers for late mortality are early hypo-tension, volume of hemorrhage, multipleorgan failure, and infections such as pneu-monia and sepsis.

HypothermiaHypothermia, which occurs frequently during

severe trauma, is associated with an increased riskof uncontrolled bleeding and increased mortality.Hypothermia impairs platelet function, includingplatelet adhesion, aggregation, and thrombin gen-eration. In addition, the function of enzymes in-volved in the coagulation cascade is reduced by 10%,when the temperature drops by 1°C.

Also, fibrinolysis is altered in a temperature-dependent manner. In elective surgery, blood loss isincreased by 16% during mild hypothermia (35°C).In contrast to acidosis-related coagulopathy, bleed-ing problems secondary to hypothermia are rever-sible with normalization of the temperature. Thissuggests that inadvertent hypothermia should beprevented and treated aggressively.

Damage Control ResuscitationPatients with life-threatening hemorrhage

should be identified as early as possible. Typically,these patients have penetrating and blunt trauma.Trauma can occur in the abdominal cavity or the

Curr Rev Nurs Anesth 34(4):37-48, 2011 41

thorax. A combination of thoraco-abdominal traumawith major extremity trauma always triggers mas-sive hemorrhage. Severely injured patients present-ing with deep hemorrhagic shock, signs of ongoingbleeding, and coagulopathy are subject to damagecontrol surgery and damage control resuscitation.Often patients present with inaccessible major ana-tomic injury and the need for time-consuming pro-cedures concomitant with major injury outside theabdomen. This acute state prompts damage controlsurgery as part of the resuscitation efforts.

Three Components of Damage Control Resus-citation

Three components comprise the resuscitationefforts. First, an abbreviated resuscitative lapa-rotomy or thoracotomy for control of bleeding isundertaken. This procedure is followed by restitu-tion of blood flow where necessary and simultan-eously there is an ongoing effort to control contam-ination. The primary surgery should be achieved asquickly as possible without spending unnecessarytime on traditional organ repairs that can be de-ferred to a later time. The abdomen, thorax, orboth are packed, and temporary closure is performed.After hemodynamic and metabolic stabilization, thepatient is taken back to the operating room forremoval of packs and definitive surgical repair.When the patient is admitted to the emergency room,damage control resuscitation is started immediatelyand continues throughout surgery and postoperativecritical care.

The damage control resuscitation per-formed by the anesthesia provider in the oper-ating room consists of two components: hypo-tensive resuscitation and hemostatic resusci-tation.

The lethal triad consists of hypothermia,acidosis, and coagulopathy and is assoc-iated with a significant increase in mor-tality.

Hypotensive Resuscitation. During hypoten-sive resuscitation, low volumes of fluids are admin-istered to achieve a safe but below normal bloodpressure until operative control of bleeding can beestablished. The goal is to minimize rebleedingby avoiding dislodging newly formed bloodclots while tissue perfusion is maintained.This process is also referred to as permissive hypo-tension. However, the low-volume approach has itslimits. It is contraindicated in traumatic braininjury and spinal injuries. Likewise, elderly patientsand patients with chronic hypertension might nottolerate permissive hypotension.

Hemostatic Resuscitation. Hemostatic resus-citation is started simultaneously with hypotensive

resuscitation. It involves aggressive delivery of bloodproducts, which begins prior to any laboratory-defined anemia or coagulopathy. Blood componentsare given early in the resuscitation process to restoreboth perfusion and normal coagulation function,while minimizing crystalloid use. Restricting in-fusion of crystalloids prevents further dilutionof already deficient coagulation factors.

The following blood components must be avail-able to successfully perform massive transfusion:red blood cells (RBCs), fresh frozen plasma (FFP),platelet concentrate, cryoprecipitate, and, undercertain circumstances, factor Vila. As an alternativeto blood components, whole fresh blood can be in-fused. Auto-transfusion devices like cell savers areuseful to reduce the transfusion of allogenic RBCs.

Damage control resuscitation is per-formed by rewarming the core, by correct-ing the acid-base imbalance, by correctingthe coagulopathy, and by optimizing theventilation and hemodynamic status.

Blood Components for Massive TransfusionRed Blood Cells. RBCs are the most utilized

component during massive transfusion. RBCs havea hematocrit of about 55% and a volume of about355 ml. If time allows, RBCs should be typed andcrossed for the patient. If transfusion must bestarted immediately, 0 negative blood should beadministered. RBCs are stored at refrigerator tem-peratures. Thus, they need to be rewarmed duringtransfusion. All rapid infusion devices used duringmassive transfusion automatically warm blood com-ponents to core body temperature. This preventsfurther aggravation of inadvertent hypothermia.

The primary functional role of RBCs is to serveas an oxygen carrier to the tissues due to theircontent of hemoglobin. Erythrocytes also play animportant role in hemostasis. They allow for mar-ginalization of platelets towards the capillary walland endothelium. They also modulate the functionalresponsiveness of activated platelets and supportthrombin generation.

A hemoglobin value of 7-9 g/dL (70-90 g/L)should be maintained during massive transfusion.In patients with a history of cardiac disease, thetransfusion trigger should be set at hemoglobinvalues < 10 g/dL (100 g/L).

Fresh Frozen Plasma Each unit of FFP comesat a volume of 200 mL. FFP contains all clottingfactors, including fibrinogen. FFP must be compat-ible with A, B, and 0 blood types; AB is the universaltype since it lacks anti-A and anti-B antibodies.

FFP is stored at -30°C. It takes about 20 min-utes to thaw a unit of FFP to get it ready for use.After thawing, the activity of labile clotting factors(such as factor V and VIII) decline gradually. FFP

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,

can be thawed and stored at 4°C for 24 hours to beavailable for immediate use without losing most ofits hemostatic capacity.

Platelets. Thrombocytes are offered as randomdonor platelets, which are pooled from multipledonors, or single donor platelets separated by apher-esis; the volume of a single donor unit equals thevolume of 4-6 units of random donor platelets.

Platelets are stored at room temperature and arestirred during storage to prevent clotting. Plateletshave a very short shelf life of five days. Each sixpack of random donor platelets or one apheresis unitwill increase the platelet count by about 20,000/uL,provided there is no further blood loss. A plateletcount of more than 50,000/uL should be the goalduring massive transfusion. Thus, the transfusiontrigger for platelets should be a platelet count below50,000/uL. Below this, platelet function decreasesexponentially. If degradation products are increasedor if there is evidence of DIG, a platelet countbelow 75,000/uL should act as transfusion trigger.Patients with concomitant traumatic brain injuryshould be given a transfusion if their platelet countis less than 100,000/uL.

Current data suggest to use a FFP:RBC:plateleticryoprecipitate ratio of 1:1:1:1 inmassively transfused patients.

Fibrinogen (Cryoprecipitate). Fibrinogen isa protein normally synthesized in the liver. Fibrin-ogen plays a crucial role in the final steps of thecoagulation process. During progressive blood loss,fibrinogen appears to represent the coagulationfactor first reaching a critical low threshold level.The decrease in fibrinogen may emerge before thedevelopment of significant thrombocytopenia. Inaddition, hemodilution with colloid plasma expand-ers predisposes patients to the development of afunctional fibrinogen deficiency.

Cryoprecipitate is derived from pooled humanplasma. It contains factor \TII, fibronectin, vonWillebrand factor, factor Xin, and fibrinogen.Cryoprecipitate will raise critical levels of fibrinogenduring massive bleeding. Ten single bags of cryo-precipitate derived from units of whole blood typ-ically raise the patient's plasma fibrinogen level by60 to 100 mg/dL (1.8 to 2.9 umol/L).

Typically, 10 units of Cryoprecipitate are admin-istered during massive transfusion. Repeat dosesare guided by laboratory assessment of fibrinogenlevels.

Recombinant Factor Vila. Factor VII is oneof the central proteins in the coagulation cascade.Factor VII is produced in the liver and is Vitamin Kdependant. The role of factor VII is to initiate theprocess of coagulation (the extrinsic pathway) inconjunction with tissue factor (TF). TF is found onthe outside of blood vessels so it is normally not

exposed to the bloodstream. When a vessel injuryoccurs, factor VII binds to TF and is activated tofactor Vila.

Factor Vila is used in treatment of massivehemorrhage. It is effective in reducing blood trans-fusion requirements modestly in blunt trauma cases.In combat casualties with massive transfusion re-quirements, the early use of factor Vila was assoc-iated with decreased transfusion requirements.

The rationale for the use of factor VIIA inhemorrhage is that it will only induce coagulation inthose sites where TF is also present. Using factorVila during massive transfusion is an off-labeltreatment. However, this treatment has beenimplemented in both military and civilian massivetransfusion protocols. The indication in traumacenters may thus be major bleeding persisting inblunt trauma despite standard attempts to controlbleeding and best-practice use of blood components.When the administration of factor VII is considered(see Table 4), platelet levels should be >50,000/uLand fibrinogen levels should be at least 50 to 100mg/dL (1.5 to 2.4 umol/L).

What Is theOptimal Ratio of Blood Products

in Massive Transfusion?Historically, patients with major bleeding from

traumatic injury were treated with an FFP to RBCratio of 1:3. FFP was recommended if the PTT was1.5 times the control value or the INR was > 2. Theinitial recommended dose was 10-15 mL/kg FFP. Inaddition, crystalloids and colloids were given in largequantities.

Although there are no prospective, randomizedcontrolled trials about the optimal ratio of bloodproducts available, a large number of retrospectiveanalyses in civilian and military trauma patients hasdemonstrated an increased survival rate with higherratios of FFP to RBC (FFP:RBC). Since then, trans-fusion guidelines suggest an "aggressive" ratio of 1:1(FFP:RBC). This ratio is complemented by one unit

Table 4Factor Vila Can Be Used If

Surgical approach is promising tostop surgical bleedingBest-practice use of blood productsis warranted with RBCs, platelets,FFP, cryoprecipitate/fibrinogenresulting in:• Hct above 24%• Platelets > 50,000/uL• Fibrinogen > 50 to 100 mg/dL

(1.5 to 2.4 umol/L)

Curr Rev Nurs Anesth 34(4):37-48, 2011 43

of pooled platelets and 10 units of cryoprecipitate.All blood products should be given early in the courseof damage control resuscitation. At the same time,the administration of crystalloids should be mini-mized. Factor VII is very expensive and should onlybe used in a civilian setting when all other bloodproducts have been given and surgical bleeding iscontrolled, but a coagulopathy continues.

Massive Transfusion ProtocolsGroups that have developed a massive trans-

fusion protocol (MTP) for severe hemorrhage reportthat an algorithmic, proactive, multidisciplinaryapproach is more effective than treatment based onthe case-by-case discretion of each provider. Severalarticles have compared transfusion practices beforeand after implementation of an MTP. Some articlesshowed a clear decline of mortality, while others didnot. Despite this controversy about a reduction inmortality after severe hemorrhage, it seems prudentto implement an MTP, because blood product useand blood bank charges decrease significantly afterMTP implementation. This finding may be a con-sequence of a more rapid and organized delivery ofblood products, which may lead to more rapid controlof coagulopathy and decreased volumes of crystal-loids. See Table 5 for a simple example of an MTP.

A massive transfusion protocol (MTP)should be adopted by centers routinelytaking care of critically injured patients.

SummaryA small portion of civilian trauma victims will

require massive transfusion. This group of patientsis likely to be coagulopathic on admission to thehospital. Early damage control surgery and damagecontrol resuscitation should be initiated.

Damage control resuscitation includes the ad-ministration of FFP and RBC in a 1:1 ratio withadditional early administration of platelets and cryo-precipitate. Simultaneously, aggressive treatmentof acidosis and hypothermia is a mainstay of dam-age control resuscitation. Factor VII may be usedto further reduce coagulopathy. Administration ofcrystalloids should be minimized, and the patient'ssystolic pressure should be kept at around 90 mmHg,

Table 5Example of a

Massive Transfusion Protocol (MTP)

• 6 units of plasma• 6 units of PRBCs• 6 packs of platelets• 10 units of cryoprecipitate

^

if no concurrent traumatic brain injury has beendiagnosed.

The implementation of an MTP reduces hospitalcosts and may improve outcome in hemorrhagingpatients. An MTP should be a multidisciplinaryprotocol tailored to the resources of the institutionand the needs of the community.

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Dente CJ: Early predictors of massive transfusion inpatients sustaining torso gunshot wounds in a civilianlevel I trauma center. J Trauma 2010; 68(2): 298-304.

Johansson PI: Hemostatic resuscitation for massivebleeding: the paradigm of plasma and platelets—areview of the current literature. Transfusion 2010; 50(3):701-10.

Nascimento B: Clinical review: fresh frozen plasmain massie bleedings—more questions than answers.Crit Care 2010; 14(1):202.

Nunez TC: Creation, implementation, and maturationof a massive transfusion protocol for the exsanguinat-ing trauma patient. J Trauma 2010; 68(6):1498-505.

Nunez TC: Transfusion therapy in hemorrhagic shock.Curr Opin Crit Care 2009; 15(6):536-41.

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