Hemorrhagic Shock Management in the ED

Shock is a state of inadequate cellular energy production that can be triggered by many causes. Both traumatic and nontraumatic causes of hemorrhage can lead to the development of hemorrhagic shock. Prompt recognition and attenuation of hemorrhage is paramount in preventing the onset or potentiation of hemorrhagic shock.[1]

In hemorrhagic shock, blood loss exceeds the body's ability to compensate and provide adequate tissue perfusion and oxygenation. This frequently is due to trauma, but it may result from spontaneous hemorrhage (eg, GI bleeding, childbirth), surgery, and other causes.

Most frequently, clinical hemorrhagic shock is caused by an acute bleeding episode with a discrete precipitating event. Less commonly, hemorrhagic shock may be seen in chronic conditions with subacute blood loss.

Physiologic compensation mechanisms for hemorrhage include initial peripheral and mesenteric vasoconstriction to shunt blood to the central circulation. This is augmented by progressive tachycardia. Invasive monitoring may reveal an increased cardiac index, increased oxygen delivery (ie, DO2), and increased oxygen consumption (ie, VO2) by tissues. Lactate levels, acid-base status, and other markers may provide useful indicators of physiologic status. Age, medications, and comorbid factors all may affect a patient's response to hemorrhagic shock.

Acute hemorrhage produces distinct physiologic responses depending on the magnitude and rate of hemorrhage. Hemorrhagic shock may be directly related to the initial injury but also may be exacerbated and complicated by a posttraumatic coagulopathy, termed acute traumatic coagulopathy.[1]

Failure of compensatory mechanisms in hemorrhagic shock can lead to death. Without intervention, a classic trimodal distribution of deaths is seen in severe hemorrhagic shock. An initial peak of mortality due to immediate exsanguination occurs within minutes of hemorrhage. Another peak occurs due to progressive decompensation after 1 to several hours. A third peak due to sepsis and organ failure occurs days to weeks later.

Understanding the pathophysiology of hemorrhagic shock is imperative in understanding current hemostatic and resuscitative strategies and is foundational to the development of new therapeutic options.[1]

Accidental injuries remain the leading cause of death in individuals 1-44 years of age.[7] Hemorrhagic shock is a leading cause of death among trauma patients.[8]  A majority of potentially preventable deaths after trauma are related to hemorrhage and occur early after injury, with the largest number of deaths occurring before hospital arrival. Approximately 25% of trauma deaths may be preventable through early medical and surgical interventions.[3]

Sparse data on the association between age and mortality in hemorrhagic shock show that in blunt hemorrhagic shock, mortality parallels increasing age, with the inflection point at 65 years. Multiple organ dysfunction score (MODS) and cardiac arrest uniformly predict mortality across all age groups. Craniotomy and thoracotomy are associated with mortality in middle age, whereas laparotomy is associated with mortality among the elderly.[9]

Injured patients with traumatic hemorrhagic shock often require resuscitation with transfusion of red blood cells, plasma, and platelets. Resuscitation with whole blood has been used in military settings, and its use is increasingly common in civilian practice.[10]

Sparse data on the association between age and mortality in hemorrhagic shock show that in blunt hemorrhagic shock, mortality parallels increasing age, with the inflection point at 65 years. Multiple organ dysfunction score (MODS) and cardiac arrest uniformly predict mortality across all age groups. Craniotomy and thoracotomy are associated with mortality in middle age, whereas laparotomy is associated with mortality among the elderly.[9]

A majority of potentially preventable deaths after trauma are related to hemorrhage and occur early after injury, with the largest number of deaths occurring before hospital arrival. Approximately one-fourth of trauma deaths may be preventable through early medical and surgical interventions. Interventions dedicated to bleeding control and hemostatic resuscitation have demonstrated merit in decreasing hemorrhagic injury mortality.[3]

Advancing these novel strategies to the casuality in the prehospital phase of care, particularly in tactical or austere environments, may prove beneficial for hemorrhage mitigation to temporize the window of survival to definitive care. Future studies of resuscitation and survival after traumatic injury must include analysis of prehospital deaths to fully understand the outcomes of early interventions.[3]

History taking should address the following:

• Specific details of the mechanism of trauma or other causes of hemorrhage are essential.

• A history of bleeding disorders and surgery should be obtained.

• Prehospital interventions, especially administration of fluids, and changes in vital signs should be noted. Emergency medical technicians and paramedics should share this information.

Findings at physical examination may include the following:

• Head, ears, eyes, nose, and throat: Sources of hemorrhage usually are apparent. Blood supply of the scalp is rich and can produce significant hemorrhage. Intracranial hemorrhage usually is insufficient to produce shock, except possibly in very young individuals.

• Chest:  Hemorrhage into the thoracic cavities (pleural, mediastinal, pericardial) may be discerned at physical examination. Ancillary studies often are required for confirmation. Signs of hemothorax may include respiratory distress, decreased breath sounds, and dullness to percussion. Tension hemothorax, or hemothorax with cardiac and contralateral lung compression, produces jugular venous distention and hemodynamic and respiratory decompensation. With pericardial tamponade, the classic triad of muffled heart sounds, jugular venous distention, and hypotension often is present, but these signs may be difficult to appreciate in the setting of an acute resuscitation.

• Abdomen: Injuries to the liver or spleen are common causes of hemorrhagic shock. Spontaneous rupture of abdominal aortic aneurysm (AAA) may cause severe intra-abdominal hemorrhage and shock. Blood irritates the peritoneal cavity; diffuse tenderness and peritonitis are common when blood is present. However, the patient with altered mental status or multiple concomitant injuries may not have the classic signs and symptoms at physical examination. Progressive abdominal distention in hemorrhagic shock is highly suggestive of intra-abdominal hemorrhage.

• Pelvis: Fractures can produce massive bleeding. Retroperitoneal bleeding must be suspected. Flank ecchymosis may indicate retroperitoneal hemorrhage.

• Extremities:  Hemorrhage from extremity injuries may be apparent, or tissues may obscure significant bleeding. Femoral fractures may produce significant blood loss.

• Nervous system: Agitation and combativeness may be seen at initial stages of hemorrhagic shock. These signs are followed by a progressive decline in level of consciousness due to cerebral hypoperfusion or concomitant head injury.

Coagulopathy may occur in severe hemorrhage. Fluid resuscitation, although necessary, may exacerbate coagulopathy. Sepsis and multiple organ system failure may occur days after acute hemorrhagic shock. Death may result.

Intravenous access and fluid resuscitation are standard. However, this practice has become controversial. For many years, aggressive fluid administration has been advocated to normalize hypotension associated with severe hemorrhagic shock. Studies of urban patients with penetrating trauma have shown that mortality increases with these interventions; study findings call these practices into question.[11, 12, 13]  

Resuscitation with crystalloid solutions has been shown to put patients with hemorrhagic shock at risk for marked acidosis and to iatrogenically worsen the lethal triad of coagulopathy, hypothermia, and acidosis. Lactated Ringer’s resuscitation has caused an increase in lactate levels, and normal saline has negatively affected the base deficit.[12, 13, 14, 15, 16, 17]  Reversal of hypotension prior to achievement of hemostasis may increase hemorrhage, dislodge partially formed clots, and dilute existing clotting factors. Findings from animal studies of uncontrolled hemorrhage support these postulates. These provocative results raise the possibility that moderate hypotension may be physiologically protective and should be permitted, if present, until hemorrhage is controlled. These findings should not yet be clinically extrapolated to other settings or etiologies of hemorrhage. The ramifications of permissive hypotension in humans remain speculative, and safety limits have not yet been established.

In a study of patients who received 7.5% NaCl (HS), 7.5% NaCl/6% Dextran 70 (HSD), or 0.9% NaCl (normal saline [NS]) in the prehospital setting, treatment with HS/HSD led to higher systolic blood pressure, sodium, chloride, and osmolarity at admission, whereas lactate, base deficit, fluid requirement, and hemoglobin levels were similar in all groups. HSD-resuscitated patients had higher international normalized ratio values at admission and greater hypercoagulability. Prothrombotic tissue factor was elevated in shock treated with NS but was depressed in both HS and HSD groups. HSD patients had the worst imbalance between procoagulation/anticoagulation and profibrinolysis/antifibrinolysis, resulting in increased hypocoagulability and hyperfibrinolysis.[13]

Damage control strategies play an important role in trauma management. One such strategy—hypotensive resuscitation—is being increasingly employed. A meta-analysis of literature and randomized controlled and cohort trials revealed significant benefits of hypotensive resuscitation relative to mortality in patients with traumatic hemorrhagic shock. It not only reduced the need for blood transfusions and the incidence of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction; it also caused a nonsignificant incidence of acute kidney injury (AKI).[18]

Laboratory studies are essential in the management of many forms of hemorrhagic shock. Baseline levels are determined frequently, but these infrequently change initial management after trauma.

Serial evaluations of the following can help guide ongoing therapy:

• CBC

• Prothrombin time and/or activated partial thromboplastin time

• Urine output rate (can help guide adequacy of perfusion)

• ABGs (levels reflect acid-base and perfusion status)

Lactate and base deficit are used at some centers to indicate the degree of metabolic debt. Clearance of these markers over time can reflect the adequacy of resuscitation.

Typed and cross-matched packed red blood cells should be ordered immediately based on clinical suspicion of hemorrhagic shock. Fresh frozen plasma and platelets may be required to correct or prevent coagulopathies that develop in severe hemorrhagic shock.

Cervical spine, chest, and pelvis radiographs are the standard screening images for severe trauma. Other radiographs may be indicated for orthopedic injuries.

Computed tomography (CT) can be used to image the appropriate region of suspected injury. CT scanning frequently is the method of choice for evaluating possible intra-abdominal and/or retroperitoneal sources of hemorrhage in stable patients (see the image below). Oral contrast material may not increase the diagnostic yield of abdominal CT scanning in blunt trauma. Scanning should not be delayed for administration of oral contrast material.[19]

CT scan of a 26-year-old man after a motor vehicle crash shows a significant amount of intra-abdominal bleeding.

Bedside abdominal ultrasonography can be very useful for rapid detection of AAA and free intra-abdominal fluid. Thoracic ultrasonographic findings can immediately confirm hemothorax or pericardial tamponade.

Directed angiography may be diagnostic and therapeutic. Interventional radiologists have had good success achieving hemostasis in hemorrhage caused by a variety of vessels and organs.

An ECG can be useful for detecting dysrhythmias and cardiac sequelae of shock.

Tissue oximetry using near-infrared spectroscopy (NIRS) shows promise for continuous noninvasive measurement of perfusion in hemorrhagic shock and other conditions.[20]

ADAMTS 13, sP-Selectin, and HSP27 have been investigated as potential prognostic markers in patients with hemorrhagic shock.[21]

Procedures

Tube thoracostomy is necessary in significant hemothorax with or without pneumothorax.

Central venous access facilitates fluid resuscitation and monitoring of central venous pressure and is necessary if peripheral intravenous access is inadequate or impossible to obtain.

Diagnostic peritoneal lavage is used to detect intra-abdominal blood, fluid, and intestinal contents. It is sensitive but is not specific for abdominal injury. It is not used to evaluate the retroperitoneum, which can hold significant hemorrhage, and it does not identify the source of hemorrhage.

Standard care consists of rapid assessment and expeditious transport to an appropriate center for evaluation and definitive care.

Intravenous access and fluid resuscitation are standard. However, this practice has become controversial. For many years, aggressive fluid administration has been advocated to normalize hypotension associated with severe hemorrhagic shock. Studies of urban patients with penetrating trauma have shown that mortality increases with these interventions; study findings call these practices into question.[11, 12, 13]

Resuscitation with crystalloid solutions has been shown to put patients with hemorrhagic shock at risk for marked acidosis and to iatrogenically worsen the lethal triad of coagulopathy, hypothermia, and acidosis. Lactated Ringer’s resuscitation, elevated lactate levels, and normal saline negatively affect the base deficit.[12, 13, 14, 15, 16, 17]

Reversal of hypotension prior to achievement of hemostasis may increase hemorrhage, dislodge partially formed clots, and dilute existing clotting factors. Findings from animal studies of uncontrolled hemorrhage support these postulates. These provocative results raise the possibility that moderate hypotension may be physiologically protective and should be permitted, if present, until hemorrhage is controlled. These findings should not yet be clinically extrapolated to other settings or etiologies of hemorrhage. The ramifications of permissive hypotension in humans remain speculative, and safety limits have not yet been established.

In a study of patients who received 7.5% NaCl (HS), 7.5% NaCl/6% Dextran 70 (HSD), or 0.9% NaCl (normal saline [NS]) in the prehospital setting, treatment with HS/HSD led to higher systolic blood pressure, sodium, chloride, and osmolarity at admission, whereas lactate, base deficit, fluid requirement, and hemoglobin levels were similar in all groups. HSD-resuscitated patients had higher international normalized ratio values at admission and greater hypocoagulability. Prothrombotic tissue factor was elevated in those with shock treated with NS but was depressed in both HS and HSD groups. HSD patients had the worst imbalance between procoagulation/anticoagulation and profibrinolysis/antifibrinolysis, resulting in increased hypocoagulability and hyperfibrinolysis.[13]

Bleeding associated with hemorrhagic shock is often seen in emergency medical services or in the intensive care unit. Identifying the origin of the bleeding and additional disorders helps to reveal the degree of hemorrhagic shock.[4]

Initial therapy until blood products are available needs to be differentiated to be effective in terms of hemodynamic stabilization and coagulation. Crystalloidal and colloidal solutions should be used carefully because these solutions bear risk within themselves. Treatment of acidosis and hypothermia can further reduce bleeding complications. Early and repeated monitoring of clotting should be performed simultaneously with shock therapy to permit specific treatment and substitution of coagulation factors if needed. Hemorrhagic shock therapy should be continued until bleeding is stopped.[4]

Direct the management of hemorrhagic shock toward optimizing perfusion and delivery of oxygen to vital organs.

Diagnose and treat the underlying hemorrhage rapidly and concurrently with shock management.

Initiate supportive therapy, including oxygen administration, monitoring, and establishment of intravenous access (eg, 2 large-bore catheters in peripheral lines, central venous access). Optimize intravascular volume and oxygen-carrying capacity. In addition to crystalloids, some colloid solutions, hypertonic solutions, and oxygen-carrying solutions (eg, hemoglobin-based emulsions, perfluorocarbon emulsions) are used or are being investigated for use in hemorrhagic shock.

Blood products are often required in severe hemorrhagic shock. Replacement of lost components using red blood cells (RBCs), fresh frozen plasma (FFP), and platelets may be essential. The ideal ratio of RBCs to FFP remains undetermined. Combat experience has suggested that aggressive use of FFP may reduce coagulopathies and improve outcomes.[15, 22]

Determination of the site and etiology of hemorrhage is critical for guiding further interventions and definitive care.

Control of hemorrhage may be achieved in the ED, or control may require consultations and special interventions.

In an Australian study of long-term outcomes of patients with major trauma who received massive transfusions, massive transfusion was independently associated with unfavorable outcomes. Among massively transfused patients, the authors found no significant change in measured outcomes over the study period, with a persistent 23% mortality in hospital, a 52% unfavorable GOSE (Glasgow Outcome Score—extended) at 6 months, and a 44% unfavorable GOSE at 12 months.[14]

Optimal management of trauma-related hemorrhagic shock begins at the point of injury and continues throughout all hospital settings.[5]

Resuscitation of the critically ill patient with fluid and blood products is one of the most widespread interventions in medicine. This is especially relevant for trauma patients, as hemorrhagic shock remains the most common cause of preventable death after injury. Consequently, the study of the ideal resuscitative product for patients in shock has become an area of great scientific interest and investigation. The pendulum has swung toward increased utilization of blood products for resuscitation. However, pathogens, immune reactions, and the limited availability of this resource remain a challenge for clinicians. Technological advances in pathogen reduction and innovations in blood product processing will allow us to increase the safety profile and efficacy of blood products, ultimately for the benefit of patients.[2]

Consult a general or specialized surgeon, a gastroenterologist, an obstetrician-gynecologist, an interventional radiologist, and others as required.

The fourth edition of the guideline on management of major bleeding and coagulopathy following trauma, by the pan-European Multidisciplinary Task Force for Advanced Bleeding Care in Trauma, includes the following[6] :

• Early imaging (ultrasonography or contrast-enhanced CT) should be used for detection of free fluid in patients with suspected torso trauma.

• CT assessment should be provided for hemodynamically stable patients.

• Low initial Hb should be considered an indicator for severe bleeding associated with coagulopathy.

• Repeated Hb measurements should be used as a laboratory marker for bleeding, as an initial Hb value in the normal range may mask bleeding.

• Serum lactate and/or base deficit measurements are sensitive tests to estimate and monitor the extent of bleeding and shock.

• Repeated monitoring of coagulation, using a traditional laboratory determination (prothrombin time [PT], activated partial thromboplastin time [APTT], platelet counts, and fibrinogen) and/or a viscoelastic method, should be provided.

• Target systolic blood pressure is 80-90 mm Hg until major bleeding has been stopped in the initial phase following trauma without brain injury.

• In patients with severe traumatic brain injury (TBI) (GCS ≤8), mean arterial pressure ≥80 mm Hg should be maintained.

• Fluid therapy using isotonic crystalloid solutions should be initiated in the hypotensive patient with bleeding trauma.

• Excessive use of 0.9 % NaCl solution should be avoided.

• Hypotonic solutions such as lactated Ringer’s solution should be avoided in patients with severe head trauma.

• Use of colloids should be restricted due to adverse effects on hemostasis.

• Target Hb is 7-9 g/dL.

• In initial management of patients with expected massive haemorrhage, one of the following strategies should be used: Plasma (FFP or pathogen-inactivated plasma) should be provided at a plasma-to-RBC ratio of at least 1:2 as needed, with fibrinogen concentrate and RBC according to Hb level.

• Tranexamic acid should be administered as early as possible to the trauma patient who is bleeding or is at risk of significant hemorrhage, at a loading dose of 1 g infused over 10 minutes, followed by an IV infusion of 1 g over 8 hours.

• Tranexamic acid should be administered to the bleeding patient with trauma within 3 hours after injury.

• Protocols for treatment of bleeding patients should consider administration of the first dose of tranexamic acid en route to the hospital.

• If a plasma-based coagulation resuscitation strategy is used, plasma (FFP or pathogen-inactivated plasma) should be administered to maintain PT and APTT < 1.5 times normal control values.

• Plasma transfusion should be avoided in patients without substantial bleeding.

• If a concentrate-based strategy is used, treatment with fibrinogen concentrate or cryoprecipitate should be provided if significant bleeding is accompanied by viscoelastic signs of a functional fibrinogen deficit or a plasma fibrinogen level less than 1.5-2.0 g/L.

• Initial fibrinogen supplementation of 3-4 g is used, which is equivalent to 15-20 single donor units of cryoprecipitate or 3-4 g of fibrinogen concentrate. Repeat doses must be guided by viscoelastic monitoring and laboratory assessment of fibrinogen levels.

• Platelets should be administered to maintain a platelet count above 50 × 109/L.

• Platelet count above 100 × 109/L should be maintained in patients with ongoing bleeding and/or TBI.

• Initial dose is 4-8 single platelet units or 1 apheresis pack.

Achievement of hemostasis, fluid resuscitation, and use of blood products are the mainstays of treatment. Pressor agents may be useful in some settings (eg, spinal shock), but these agents should not be substitutes for adequate volume resuscitation and blood product replacement.

Tranexamic acid (TXA) is an inexpensive antifibrinolytic drug that promotes blood clotting by preventing blood clots from breaking down. It has been shown to reduce mortality in trauma patients with uncontrolled hemorrhage.[23] Further studies are planned to determine specific recommendations for TXA administration.

Trauma remains a leading cause of death, and hemorrhage is the leading cause of preventable trauma deaths. Resuscitation strategies in trauma have changed dramatically over the last 20 years.[24]

Management of traumatic hemorrhagic shock has evolved, with increasing emphasis on damage control resuscitation principles.[25]

In the pre-damage control resuscitation (DCR) era, we used large-volume crystalloid resuscitation and packed red blood cells as primary resuscitative fluids. Now, a 1:1:1 ratio of packed red blood cells, fresh plasma, and platelets with minimal crystalloids is the preferred resuscitative strategy (DCR era). As we have changed how we resuscitate patients, the detrimental effects associated with large-volume resuscitation have also changed.[24]

Class Summary

These agents augment both coronary and cerebral blood flow during the low-flow state associated with shock.

Dopamine (Intropin)

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on dose. Lower doses predominantly stimulate dopaminergic receptors that in turn produce renal and mesenteric vasodilation. Higher doses produce cardiac stimulation and renal vasodilation

Norepinephrine (Levophed)

Used in protracted hypotension following adequate fluid volume replacement. Stimulates beta1-adrenergic and alpha-adrenergic receptors, which, in turn, increase cardiac muscle contractility and heart rate, as well as vasoconstriction; result is increased systemic BP and coronary blood flow.

Vasopressin (Pitressin)

Provides vasopressor and ADH activity. Increases water resorption at distal renal tubular epithelium (ADH effect) and promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects); however, vasoconstriction also is increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.

Epinephrine (Adrenalin, Bronitin)

Used for hypotension refractory to dopamine. Alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.