Joshua M. Glazer and Kyle J. Gunnerson
Case Presentation
A previously healthy 35 year old male presented as a Level I trauma after a motor vehicle acci- dent in which he was the restrained driver. There was extensive intrusion on the front end of the vehicle requiring extrication of the patient.
Airbag did not deploy. He was reportedly hypo- tensive and confused in the field. An 18 gauge IV was placed and a 500 mL NS bolus initiated prior to arrival. In the Emergency Department, his initial vitals were significant for a heart rate of 140 and blood pressure of 72/48. Primary sur- vey demonstrated an intact airway, bilateral breath sounds, 2+ pulses in all four extremities, and a Glasgow Coma Score (GCS) of 11 with no obvious focal disability on full exposure. The patient was pale, had a large left-sided frontal scalp contusion, and had obvious bruising of the lower chest and right abdomen. A bedside Extended Focused Assessment with Ultrasound in Trauma (E-FAST) exam showed free fluid in Morison’s pouch (Fig. 4.1). The remaining
E-FAST views showed no evidence of hemo- pneumothorax, pericardial fluid, myocardial wall-motion abnormalities, or fluid in the sple- norenal or rectovesicular spaces. Trauma- protocol chest and pelvis x-rays were negative.
Question What is the optimal approach to man- agement of this patient’s presumed traumatic hemorrhagic shock; specifically, how should intravascular access, fluid resuscitation, hemody- namic end-points, and definitive therapy be prioritized?
Answer Hemostatic resuscitation prioritizing damage control surgery & massive transfusion.
This patient is exsanguinating, presumably secondary to traumatic intraabdominal injury, and demonstrating physiology consistent with decompensated hemorrhagic shock. Injury mech- anism and physical exam findings are also con- cerning for concurrent traumatic brain injury. As with all types of shock, prioritization is given to reversal of the inciting etiology and concurrent mitigation of tissue hypoperfusion caused by the precipitating shock state.
After confirming an intact airway and bilateral breath sounds, this patient’s management appro- priately focused on cardiovascular optimization and hemodynamic support. Two additional proxi- mal 16 gauge peripheral IV’s were placed. The crystalloids which were initiated in the field were discontinued. Non-crossed O+ packed red blood
J.M. Glazer
Emergency Medicine, University of Michigan Health System, Ann Arbor, MI, USA
K.J. Gunnerson (*)
Emergency Medicine, Internal Medicine and Anesthesiology, Division of Emergency Critical Care, University of Michigan Health System,
Ann Arbor, MI, USA
e-mail: [email protected]
4
cells, along with fresh frozen plasma and pooled platelets, were rapidly hand-delivered and infused in a 1:1:1 ratio per the institutional massive trans- fusion protocol. As he is within the 3-h window, tranexamic acid is administered to inhibit fibrino- lysis. Simultaneously, electrolytes were aggres- sively repleted and his acidosis corrected. A multidisciplinary Trauma team agreed on a mean arterial pressure goal of 75 mmHg in an effort to maintain cerebral perfusion pressure in the set- ting of probable traumatic brain injury, remaining cognizant to avoid overcorrection and resultant disruption of intrinsic/protective hemostatic mechanisms.
After initial evaluation/stabilization in the Emergency Department, the patient was trans- ported first for head CT, which did not show intracranial hemorrhage, then to the operating room for exploratory laparotomy. Damage con- trol surgery, including splenectomy and partial small bowel resection without reanastamosis, was performed. The patient was then trans- ferred to the ICU with an abdominal wound vacuum device in place. Hemodynamic optimi- zation was continued, utilizing a combination of blood products, pressors, and intravenous
fluids. Markers of tissue perfusion, including central venous oxygen saturations (ScvO2) and serial lactate levels, improved and the patient was taken back to the operating room for reanastamosis and closure.
Principles of Management Hypovolemic Shock
We will first review fundamentals of the manage- ment of hypovolemic shock regardless of etiol- ogy, then focus on elements unique to treating patients with hemorrhagic shock.
Establish Adequate IV Access
Flow rates achieved for potential life-saving fluid resuscitation depend on the device used. In agree- ment with Poiseuille’s law, the ideal cannula should be a short, large-bore (at least 18 g), and placed in a proximal large vein in the upper extremity. If a central venous catheter (CVC) is the only available access, the addition of a pres- sure bag makes a greater difference on flow rate than with an equivalent peripheral cannula [1].
However, in a resuscitation setting, intraosseous (IO) access has higher first pass success and shorter procedure times, making it preferable to CVC insertion if peripheral access cannot be rap- idly obtained [2]. Of the three approved IO sites (proximal tibia, distal tibia, proximal humerus), the humerus seems to be the superior site in terms of flow rates, drug delivery, and management of infusion pain [3].
Consider Physiologic Reserve
Young healthy individuals can maintain end- organ perfusion and normotension despite sig- nificant intravascular loss as a result of their ability to sustain cardiac output through: periph- eral vasoconstriction, compensatory tachycardia, and catecholamine surge. Thus, substantial tachycardia and cool extremities should be rec- ognized as markers of imminent decompensation and cardiovascular collapse in these individuals [4]. Conversely, systemic diseases (e.g. chronic kidney disease, hypertension, diabetes, cirrhosis,
Fig. 4.1 Extended Focused Assessment with Ultrasound in Trauma (E-FAST) scan showing free fluid surrounding the liver border in a polytrauma patient (Reproduced with permission of Huang and Fung)
chronic heart failure) and/or pharmacotherapies (e.g. alcohol, antihypertensives, anti- arrhythmics, β-blockers, steroids, insulin) can both limit phys- iological reserve and also delay detection of shock when patients do not manifest classic signs of hypovolemia.
Monitor Volume Responsiveness
Fundamentally, “fluid responsiveness” means that stroke volume (and thus cardiac output, given stable heart rate) will improve if fluids are administered. Administering fluid to a volume unresponsive patient can negatively affect car- diac output directly and has other potential side effects such as pulmonary edema, abdominal compartment syndrome, and cerebral edema.
Traditionally an increase in stroke volume of 10–15 % after receiving an adequate bolus (rapid infusion of at least 250 cc) is considered a posi- tive test of volume responsiveness [5]. Several techniques and technologies exist to help make this determination without actually administer- ing a volume expander, but each has its own unique challenges and limitations. Please refer to the “Undifferentiated Shock” chapter for a more detailed discussion.
Administer the Appropriate Fluid(s)
The ideal fluid used to replete intravascular depletion is very much dependent on the precipi- tating etiology. With gastrointestinal losses, thoughtful repletion of electrolytes is indicated.
With acute blood loss, sanguineous resuscitation is clearly preferable. Importantly, tissue perfu- sion and oxygen delivery are the goals, and that optimization of cardiac output and oxygen carry- ing capacity are the means.
Track Endpoints of Resuscitation
Normalization of vital signs alone is insuffi- cient evidence of resolution of shock; indeed, poor tissue perfusion can often persist and lead to ongoing accumulation of oxygen debt and tissue damage (see Fig. 4.2). More appro- priate markers, which account for perfusion of the microcirculation, include central venous oxygen saturation (ScvO2) and lactate clearance [6, 7].
Hemorrhagic Shock
Hemostatic resuscitation refers to the process of restoring and sustaining normal tissue perfusion to the patient presenting in uncontrolled hemor- rhagic shock, with an emphasis on preservation of effective clotting.
Expedite Anatomic Control of Bleeding Immediate control of ongoing hemorrhage is always the first priority. This may simply require direct pres- sure or other straightforward maneuvers for brisk external bleeds (e.g. staple closure for scalp wound or nasal pack for epistaxis). Depending on the source, however, Gastroenterology, Interventional Radiology, or Surgery consultation may be required for specific hemostatic interventions.
Utilize Damage Control Surgery
The initial surgery on a hemodynamically unsta- ble, actively bleeding patient should be focused on anatomic control of bleeding, with repair of less significant injuries or time-intensive proce- dures deferred. Once hemostasis is achieved, the patient is transferred to the intensive care unit for completion of resuscitation [8]. Subsequent oper- ative interventions are later performed once the patient is hemodynamically stable.
Allow for Permissive Hypotension
While the goal of resuscitation in general is to restore normal systemic oxygen delivery, during early resuscitation the advantage of reducing ischemia must be weighed against the iatrogenic prolongation of hemorrhage. Indeed, attempting to achieve normotension during active hemor- rhage consistently increases mortality [9, 10]. In penetrating trauma patients, resuscitation to a tar- get minimum MAP of 50 mmHg, rather than 65 mmHg, significantly decreases postoperative coagulopathy and lowers the risk of early postop- erative death and coagulopathy [11].
Correct and Reverse Augmenting Factors of Coagulopathy and Shock
In the exsanguinating patient, the so-called “lethal triad” of coagulopathy, acidosis, and hypothermia predict morality and must be corrected (see Fig. 4.3).
Several studies have demonstrated that patients with altered coagulation function at the time of hos- pital admission have substantially worse outcomes than similar patients who are not coagulopathic, even when controlling for degree of injury [12, 13].
Minimize Crystalloid Administration Indiscriminate fluid administration during uncon- trolled hemorrhage is associated with increased bleeding. Relative arterial hypertension caused by augmented cardiac output via the Frank- Starling relationship, forces more fluid out of the damaged circulation, and can “wash away” early clots. Furthermore, asanguineous crystalloids dilute the concentration of red cells, clotting fac- tors, and platelets, impairing both oxygen carry- ing capacity and the clotting cascade [14].
Exogenous fluids are also likely to be cooler than body temperature, contributing to hypothermia.
Finally, rapid administration of crystalloids dam- ages the endothelial glycocalyx, leading to increased extravasation [15].
Preserve Formed Clot with Antifibrinolytics
The CRASH-2 trial randomized 20,000 trauma patients worldwide to receive either placebo or tranexamic acid, and demonstrated a significant survival benefit with this therapy when administered within 3 h of injury. Interestingly, there was no dif- ference in transfusion requirements between the
Delivery dependent VO2
Delivery independent VO2
VO2 VO2
SVO2 OER Lactate
DO2crit
DO2 SVO2
OER Lactate
Fig. 4.2 The relationship between oxygen delivery and oxygen consumption in shock. When DO2 decreases to less than the value for critical delivery (DO2crit), oxygen con- sumption (VO2) is linearly dependent on the delivery of oxygen to the tissues (DO2). In the delivery-dependent region, oxygen extraction ratio is maximal and anaerobic metabolism increases with an associated increase in lactate and decrease in SVO2. This region to the left of DO2crit is
where oxygen debt starts to accumulate. DO2 = CaO2 × CO (normal range: 460–650 ml/min/m2); VO2 = CO × (CaO2 – CVO2) (normal range: 96–170 ml/min/m2); CaO2 (arterial oxygen content) = (Hb × 1.34 × SaO2) + (0.003 × PaO2);
CVO2 = (Hb × 1.34 × SVO2) + (0.003 × PVO2). CO cardiac output, PaO2 arterial oxygen tension, Hb hemoglobin.
SVO2 normal range: 70 % (±5 %) [34]
Fig. 4.3 The so-called “lethal triad” whereby the combi- nation of hypothermia, acidosis, and coagulopathy con- tribute toward mortality in hemorrhagic shock. Iatrogenic etiologies for worsening hemorrhage include use of crys- talloids and packed red blood cells (PRBC). Both directly worsen hypothermia if not warmed and contribute to dilu- tional coagulopathy, the latter if platelets and fresh frozen plasma are not concurrently infused
groups, suggesting that tranexamic acid may have effects in addition to antifibrinolysis. The earlier the drug was administered, the more positive the effect [16].
Replace Losses via Transfusion Therapy In the setting of brisk hemorrhage, the ideal fluid of choice is fresh whole blood (FWB). Blood provides the intravascular volume expansion needed to increase cardiac output, the red blood cells necessary for oxygen carrying capacity, and contains the platelets and clotting factors which enable hemostasis [17]. Importantly, hemoglobin and hematocrit do not change in acute hemorrhage; indeed, these measurements reflect concentrations of red blood cell content, and will not be affected until compensatory fluid shifts from the intra- and extra-cellular spaces dilute the blood.
Evidence Contour
Several aspects regarding the management of hypovolemic and hemorrhagic shock remain without clear consensus.
Hypovolemic Shock
The ideal fluid for hypovolemic shock secondary to asanguineous losses should reliably expand intravascular volume; have a sustained effect without accumulation in tissues, and replete whole-body deficits, while minimizing side- effects (electrolyte disturbances, third-spacing, acidosis, hemodilution) and cost. Unfortunately, no such fluid exists; so much debate exists sur- rounding which “non-ideal” fluid to use.
Normal Saline vs Balanced Solutions Normal saline has traditionally been the most widely-used crystalloid in the United States.
Increasing evidence, however, suggests that exces- sive chloride loads are associated with negative outcomes. Among patients with systemic inflam- matory response syndrome (SIRS), chloride- restrictive fluid resuscitation is associated with
lower in-hospital mortality [18]. Furthermore, implementation of a chloride- restrictive resusci- tation is associated with a significant decrease in the incidence of acute kidney injury and use of renal replacement therapy [19]. Commercially available chloride-restrictive fluids include the crystalloids Lactated Ringers and Plasma-Lyte, as well as the colloids albumin and several syn- thetic gelatin- or hydroxyethyl starch (HES)- based preparations.
Role of Albumin
The Saline versus Albumin Fluid Evaluation (SAFE) study showed no significant difference in rate of death or development of organ failure among ICU patients randomized to normal saline or albumin resuscitation. Subgroup analysis sug- gests that use of albumin in patients with trau- matic brain injury was associated with a significant increase in rate of death at 2 years while albumin is associated with a significant decrease in the rate of death at 28 days in patients with severe sepsis [20].
Use and Timing of Pressors
Even in patients with “pure” hypovolemic shock, vasopressors can and should be used as a bridge while volume is infused and then titrated off as the volume deficit is overcome [21]. The aim is to preserve coronary perfusion pressure (CPP) (aor- tic diastolic pressure (ADP) – pulmonary artery wedge pressure (PAWP)) and thus prevent isch- emic injury and secondary cardiogenic shock.
Many experts suggest that a target ADP of 35–40 mmHg is likely adequate; however, in patients with preexisting conditions that increase baseline PAWP (e.g. pulmonary hypertension), the ADP goal should be correspondingly increased [22, 23].
Hemorrhagic Shock
Adequately powered clinical trials addressing the question of optimal resuscitation of massively bleeding patients are lacking. Instead, a large num- ber of retrospective studies and systematic reviews concerning this topic have been published,
although the interpretation of the currently avail- able data differs substantially. Figure 4.4 demon- strates a theoretical framework for the treatment of hemorrhagic shock. Figure 4.5 incorporates this information with logistical considerations neces- sary for implementing an institutional massive transfusion protocol.
Massive Transfusion Protocol
Studies of both military and civilian trauma patients have demonstrated that those receiving high ratios of both fresh frozen plasma (FFP) and platelets (PLT) to red blood cells (RBC) have the highest survival, suggesting that the ideal transfusion ratio
is 1:1:1 FFP:PLT:RBC. However, close inspection of many of these studies reveals important limita- tions in their interpretation, namely a prominent effect of survivor bias [24]. While the optimal mas- sive transfusion protocol ratio remains elusive, it does appear that an early and more balanced approach to transfusion is associated with improved outcomes [25].
Ionized Calcium Repletion
Hypocalcemia can complicate massive transfu- sion as a result of the citrate anticoagulant in blood products (FFP&PLT > PRBC). Formation and stabilization of fibrin polymers is dependent
Monitoring
Anti- fibrinolytics
Transfusion therapy
Anatomic control
30 min Uncontrolled hemorrhage
Control of hemorrhage Additional RBC based off Hgb level Goal-directed VHA-guided transfusion
VTE prophylaxis Tranexamic acid according to CRASH2 and/or VHA
Correct: Temp, Ca2+, K+, PaO2, PaCO2 Start of
hemorrhage Hemostasis
Ratio 1: 1: 1
RBC: FFP: PLT
60 min Time
Shock Reversal: pH, lactate, ScvO2
Fig. 4.4 One reasonable algorithm for treatment of hem- orrhagic shock incorporating principles of hemostatic resuscitation. Of primary importance is anatomic control of bleeding. Concurrently, goal-directed transfusion of blood products and anti-fibrinolytics are administered to preserve cardiac output, oxygen carrying capacity, and the ability to form and preserve clots. As with any shock state correction of electrolyte abnormalities, hypothermia, and
oxygenation/ventilation issues is indicated while tracking endpoints of resuscitation including serum pH, lactate, and ScvO2. RBC red blood cells, FFP fresh frozen plasma, PLT platelets, Hgb hemoglobin, VHA viscoelastical hemostatic assay, VTE venous thromboembolism, Ca2+
serum calcium, K+ serum potassium, PaO2 partial pressure of oxygen in blood, PaCO2 partial pressure of carbon dioxide in blood, ScvO2 central venous oxygen saturation
on ionized calcium; additionally, decreased intra- cellular calcium concentration negatively affects all platelet-related activities. Equally importantly, myocardial contractility and systemic vascular resistance are compromised at low ionized cal- cium levels. Taking into account beneficial car- diovascular and coagulation effects, ionized calcium levels should be maintained above 0.9 mmol/l [26].
Point-of-Care Monitoring the Hemostatic System
Conventional laboratory tests of coagulation are insensitive in detection acquired coagulopathy or in guiding procoagulant therapy [27].
Viscoelastical hemostatic assays (VHAs), includ- ing thrombelastography (TEG®) and rotational thrombelastometry (ROTEM®), provide rapid
information regarding platelet aggregation, clot strengthening, fibrin cross-linking, and fibrinoly- sis, and thus more accurately assess global hemo- static potential. Goal-directed transfusion utilizing VHAs have been reported to reduce bleeding, significantly diminish transfusion requirements, and improve outcomes in cohort studies [28].
Invasive Non-surgical Hemorrhage Control
In moribund or arresting patients with exsanguinat- ing noncompressible hemorrhage in the chest, abdomen, or pelvis, resuscitative thoracotomy has traditionally been the intervention of choice in the emergent setting. Unfortunately, after controlling for relatively easily reversible causes of traumatic obstructive shock (tension pneumothorax and
Intravenous access – 2 large bore IVs and Centrol Venous Cath Labs: T&S, CBC, Plts, INR, PT, PTT, Fibrinogen, Electrolytes, BUN/Creatinine, ionized calcium
Continual monitoring: VS, U/O, Acid-base status Aggressive re-warning
Prevent / Reverse aicdosis
Correct hypocalcemia: CaGluconate or Cacl Target goal ionized calcium 1.2 –1.3 If use CaCl 1 gm, give slowly IV Repeat lab testing to evaluate coagulopathy Stop crystallcid - avoid dilutional coagulopathy
Cell salvage
Heparin reversal: Protamine 1mg IV/100 U heparin
Warfarin reversal: Vitamin K 10 mg IV; Consider Prothromin Comp Chronic Renal Failure + VW Factor; DDAVP 0.3 mg/kg IV x 1 dose Consider antifibrinoclytics:
Tranexamic acid 1 gm bolus plus infusion 1 gm over 8 hrs Arricar 5 gm IV bolus then 1 gm/hr IV infusion
Anesthesia pager *****
Additional help Other considerations:
Appropriate Initial Interventions:
Rapid Response Team pager *****
General Guidelines for Lab-based Blood Component Replacement in Adults:
Product RBCs FFP Platelets
Cryoprecipitate Fibrinogen <
100 Two 5-packs
Cryoprecipitate
Notify BB & return any unused blood ASAP
Resume standard orders D/C MTP Electronic order
Stop MTP
Repeat Labs
Consider rFVIIa If persistent coagulopathy 90 m/kg dose YES
NO Hemostasis &
resolution of coagulopathy?
Clinical Contact calls BB at
***** for another MTP pack
** MD can adjust pack based on labs PRN Provides name of clinical contact person to Blood Bank (BB)
Clinical Team Activates MTP & Designates Clinical Contact Adult: 4U RBCs in <4 hours and ongoing bleeding
Identify and Manage Bleeding
Massive Transfusion Protocol (MTP)
(Surgery, Angiographic Embolization, Endoscopy)
Clinical Contact phones Blood Bank (BB) at ***- **** and:
Provides MR#, sex, name, location of patient
Records name of BB contact, calls if location/contact information changes Sends person to pick up the cooler
Ensures that MTP protocol elcetronic order is entered
BB Prepares MTP Pack; Transfuse as 1:1:1 Ratio MTP Pack: 6U RBCs; 4U FFp ; One (1) 5-pack Platelets
CBC, Platelets INR/PT, PTT Fibrinogen AbG (Ionized Calcium, Potassium, Lactate, Hematocrit)
< 100,000 One 5-pack Plts INR > 1.5 4 units FFP No threshold MD discretion Threshold Dose
Trauma Chief pager *****
General Guidelines for Lab-based Blood Component Replacement in Adults:
Fig. 4.5 An institutional Massive Transfusion Protocol detailing the initial stabilization steps, necessary contact information, relevant electronic medical record orders,
component blood products, and triggers for activation and deactivation