EM@3AM: Systematic Approach to Massive Hemorrhage and Nuances in Special Patient Populations

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

General principles in the approach to massive hemorrhage

Definition of Massive Hemorrhage:

• Definitions of major hemorrhage include:
  • Loss of more than one circulating blood volume within 24 h, loss of 50% of total blood volume in < 3 h, or bleeding in excess of 150 mL/min.¹
• These values can be difficult to quickly assess and measure in a fast-paced clinical scenario. Determining whether a patient has massive hemorrhage or not should primarily be based on the “you will know it when you see it” approach.

Evaluation:

• Look for clear and obvious active bleeding.
• Remember the “SCALPR” mnemonic to identify locations of massive blood loss.
  • Scalp/Street
  • Chest
  • Abdomen
  • Long bones
  • Pelvis
  • Retroperitoneum

Lab Testing:

• CBC, PTT, PT/INR, Fibrinogen
• CMP, Mg, Phos, Ionized Ca, Lactate
• Type and Cross
• ABG or VBG
• Beta-hCG, if female of childbearing age
• Thromboelastography (TEG)/ rotational thromboelastometry (ROTEM) may be used for guided resuscitation of coagulopathy if available at your facility.
  • The usage of TEG remains controversial and studies evaluating its effectiveness in the setting of trauma and other medical presentations are ongoing.^2-5
  • If TEG usage is considered, it should only be employed following initial resuscitation of your bleeding patient.
  • For more information on TEG and ROTEM please refer to this previous post:
    • https://www.emdocs.net/thromboelastogram-teg-five-minute-primer-emergency-physician/

Imaging:

• X-ray
  • Obtain a chest x-ray and pelvis x-ray in the setting of trauma.
  • A chest x-ray can aid in quickly identifying hemothorax/pneumothorax. A pelvis x-ray can identify pelvic fractures, namely open book pelvic fractures that are prone to causing pelvic hemorrhage.
  • Obtain extremity imaging if suspicious for injury, as long bone fractures pose a potential source of hemorrhage.
• Ultrasound
  • Perform a Rapid Ultrasound for Shock and Hypotension (RUSH exam) for undifferentiated hypotension. (https://www.emdocs.net/rush-protocol/)
  • In the setting of trauma, perform an extended focused assessment with sonography in trauma (EFAST) exam in hemodynamically unstable patients.
• Computed Tomography Scan (CT Scan)
  • Stabilization of massive hemorrhage should occur prior to obtaining CT scan imaging.
  • What scans to order should be guided by clinical judgment.
  • In the setting of polytrauma, a multiphasic protocol should be used for best observation of bleeding in the arterial phase and solid abdominal organ injury in the homogeneous portal venous phase.⁶

Management:

• Obtain Source control
  • First step in massive hemorrhage management is to obtain source control.
  • Apply a tourniquet proximal to the wound until bleeding is controlled for extremity injuries with profuse bleeding. Consider a figure of 8 suture placement for hemorrhage control.
  • Reduce long bone fractures or apply a pelvic binder if an open book pelvic fracture is suspected, ensuring that the binder is placed over the greater trochanters. (https://www.emdocs.net/unstable-pelvic-trauma-patient-ed-presentations-evaluation-and-management/)
  • For non-extremity bleeding use direct pressure, a pressure dressing or consider packing a wound with TXA soaked gauze if appropriate.
  • Oftentimes source control for non-compressible hemorrhage and intracavitary hemorrhage cannot be obtained and you must proceed with stabilizing measures until definitive care by a specialist.
  • Many patients may require definitive management in the OR or IR suite so consider early engagement of these specialists.

• Obtain adequate IV access for rapid blood product administration
  • Prompt IV access is critical to a successful resuscitation.
  • If early IV access is difficult, place an intraosseous (IO) line  (https://www.emdocs.net/feelin-it-in-my-bones-a-review-of-intraosseous-access-in-the-emergency-department/ ) until more definitive IV access can be obtained.
    • The proximal tibia, humeral head, and sternum are the preferred sites in adults.
    • The distal femur, proximal tibia, and distal tibia are preferred sites for infants and neonates.
    • Blood can be pressure bagged through an intraosseous catheter. ⁷
  • Rapid administration of blood products is essential in the management of massive hemorrhage.
    • Per Poiseuille’s law, laminar flow will be greatest through a cylinder that is wide and short.⁸
    • In the earliest stages of hemorrhage resuscitation a decision must be made regarding what is the largest and most quickly obtained IV access. This will vary based on each individual physician and nursing team as well as vary by patient.
  • Rapid infusion systems, if available, should be used to administer blood products at maximum driving pressure, having the benefit of consistent high pressure (usually 300 mmHg) delivery. They also have the added benefit of providing warming for blood products which will aid in preventing hypothermia and coagulopathy. See Figure 1. and 2. for study data regarding flow rates with rapid infusion systems.
  • In accordance with Poiseuille’s law, the length of a standard 7f triple lumen central line will provide poor flow rates and should be avoided if more effective IV access can be obtained.

• Consider Initiation of your institution’s Massive Transfusion Protocol (MTP)
  • Initiate Massive transfusion protocol (MTP) when you anticipate multiple units of blood products will be needed to stabilize a hemorrhaging patient.
  • No single decision tool has yet been shown to be useful in determining when to initiate an MTP and should be guided by your clinical judgement and your institution’s guidelines. (https://www.emdocs.net/em-cases-the-7-ts-of-massive-hemorrhage-protocols/)
  • Avoid Crystalloid administration for massive hemorrhage as crystalloid administration >500 mL is associated with worse patient outcomes.⁹
  • Current best practice suggests a 1:1:1 administration of PRBC, Platelets, and FFP. Follow institutional guidelines regarding blood product administration ratios.¹⁰
  • O+ PRBC should be used for males >16 years of age and females >50 years of age. O- PRBC should be given to all others.¹¹
  • Administration of whole blood may be superior in early mortality when compared to balanced transfusion of individual components, but this is a controversial area of ongoing research. You should follow your institution’s MTP protocol.¹²
  • 1-2 grams calcium chloride or 3-6 grams calcium gluconate should be administered per MTP round as citrate, an anticoagulant added to blood products, works by chelating calcium. The amount of blood products per MTP round will vary based on your institutional specific protocol.
  • Blood products should be warmed to a maximum of 42℃ to prevent hypothermia and coagulopathy.¹³

• Resuscitation Strategies
  • Strongly consider placement of an arterial line for accurate blood pressure measurements as you provide blood product resuscitation.
  • The decision to terminate blood product administration will be based on multiple factors.
    • Lab tests such as hemoglobin will lag behind the clinical picture and thus should not be used to guide resuscitation.
  • Evaluate the patient’s MAP with a target goal of 60-65. Take this into consideration alongside your bedside evaluation of end organ perfusion and mental status.
  • Avoiding hypotension in traumatic brain injury patients is paramount.
  • While “permissive hypotension” may be a helpful strategy in some clinical scenarios, blood product resuscitation should generally continue for a MAP of 65 and clinical improvement such as improvement in mental status and distal extremity perfusion.¹⁴
  • Once the patient is stable, as assessed by vitals sign measurements and clinical evaluation, the need for ongoing blood product administration is best guided by a “restrictive strategy.”
    • A restrictive strategy is one in which transfusion of packed red blood cells (pRBC) is administered at a threshold of 7-8 g/dL or 8.5-10 g/dL in patients with acute coronary syndrome (ACS).¹⁵

• Avoid the “Diamond of Death” (Acidosis, Hypothermia, Coagulopathy, Hypocalcemia) (https://www.emdocs.net/emdocs-podcast-episode-102-hypocalcemia-in-trauma-and-the-diamond-of-death/)

• Avoid Acidosis
  • Acidosis impairs clot formation through multiple mechanisms.¹⁶
  • Provide adequate volume resuscitation as described above to correct the underlying cause of lactic acidosis.
  • In ventilated patients you can make ventilator adjustments, including an increased ventilation rate to compensate for a metabolic acidosis in order to normalize the patient’s pH.
• Avoid Hypothermia
  • Use warmed fluids using a rapid infuser to aid in preventing hypothermia.
  • Be mindful that after exposure of the patient during a primary survey, warm blankets or external warming devices are applied to warm the patient.
• Avoid Coagulopathy
  • In the early stages of resuscitation management draw a PTT, INR, Fibrinogen levels and a TEG or ROTEM, if available.
  • Balanced transfusion of packed red blood cells (PRBCs), platelets and fresh frozen plasma (FFP) in a 1:1:1 ratio is the current best practice to avoid inducing coagulopathy by large volume blood product administration.¹⁷
  • TEG and ROTEM are non-invasive tests that quantitatively measure the ability of whole blood to form a clot.¹⁸
  • Coagulopathy correction in massive hemorrhage as guided by these point of care tests may be effective in reduction of mortality and quantity of blood products used but is an area of ongoing research.¹⁹
  • Fibrinogen levels are another important factor in correcting coagulopathy and aiding in hemostasis. Normal fibrinogen levels are generally considered to range from 2.0 to 4.5 g/L. There is currently no clear consensus on Fibrinogen levels that necessitate fibrinogen replacement, with products such as cryoprecipitate, but current best practice is to replace fibrinogen at a minimum threshold of 1.5 to 2.0 g/L. More research is needed to elucidate a clear benefit to fibrinogen replacement with blood products such as cryoprecipitate.²⁰
  • PTT and INR levels in conjunction with careful history taking are important in identifying patients with underlying coagulopathy.
  • Reversal of anticoagulants and antiplatelet medications are an important step to correcting coagulopathy in actively hemorrhaging patients.
  • Review the reversal agent recommendations for various medication categories such as vitamin K antagonists, direct thrombin inhibitors, factor Xa inhibitors, and antiplatelet medications.(https://www.emdocs.net/reversal-of-anticoagulation/)

• Avoid Hypocalcemia
  • Hypocalcemia provokes coagulopathy, acidosis and worsening hemorrhage.²¹
  • Hypothermia and administration of citrate within packed red blood cells can both decrease ionized calcium levels in the blood leading to progressively worse coagulopathy.²²
  • Obtain ionized calcium levels during the initial phase of resuscitation of massive hemorrhage but do not wait for these levels to return in the setting of large volume blood product administration.
  • Provide 1-2 grams calcium chloride or 3-6 grams calcium gluconate should be administered per MTP round. The amount of blood products that constitutes one MTP round will vary slightly based on institution protocol.

Special Caveats

Hemorrhagic Shock in the Setting of Trauma

• Consider addressing Circulation prior to Airway in hemorrhagic shock in trauma, though both may require simultaneous intervention.
• Systematic approach to massive hemorrhage must be fit into the context of an overall ABCDE (ATLS) approach to trauma
• Tranexamic Acid (TXA) may reduce mortality in adult trauma patients.
  • Data from “The CRASH-2 Trial suggest that administration of TXA in adults with evidence of massive hemorrhage may reduce mortality.²³
  • In the CRASH-2 trial 1 gram TXA was administered as a 1 gram loading dose followed by 1 gram over 8 hours in adult patients with massive hemorrhage.
  • This administration practice raises concerns for compliance issues in daily practice.
  • It is reasonable to provide a 2 gram bolus of TXA during initial traumatic resuscitation in patients in whom you are concerned for massive hemorrhage.²⁴
  • It is also important to remember that TXA administration should occur within three hours of initial injury. The earlier it is given the better with the greatest reduction in deaths seen when TXA was given less than one hour from injury.²³
    • Do not give TXA if injury occurred greater than 3 hours from presentation. Administration of TXA in this scenario is associated with an increased risk of death from bleeding.²²

Postpartum Hemorrhage

• The American College of Obstetricians and Gynecologists Clinical Management Guidelines from 2017.²⁵
  • Defines postpartum hemorrhage as blood loss greater than or equal to 1000 mL of blood or blood loss with signs of hypovolemia within 24 hours of delivery
• Similar resuscitation strategies to other forms for hemorrhagic shock
• O- blood products unless type & screen has been performed
• TXA
  • Give as soon as possible relative to bleeding onset
  • 1g IV of over 10 min, with 2nd dose 30 min later if continual bleed OR bleed restarts within 24 hrs after 1st dose.²⁶
  • Early OB/GYN consultation for surgical evaluation
• “The 4 Ts” mnemonic for potential etiologies: Tone, Trauma, Tissue, and Thrombin
  • Tone
    • Uterine atony
      • 70-80% of postpartum hemorrhage
      • Interventions include uterine massage and bimanual compression
      • Oxytocin²⁷
        • First line drug
        • 20 IU in 1 L NS at 250 ml/hr
        • 80 IU in 500 cc NS wide open
        • 10 IU IM once
      • If hemorrhage control is inadequate despite uterine massage, TXA and Oxytocin then the following may be given as 2nd line agents:
        • Misoprostol
          • 600 mcg SL
          • 1000 mcg rectally
        • Methylergonovine
          • 2 mg IM every 2-4 hr
          • Relatively contraindicated in patients with preeclampsia or HTN
        • Carboprost
          • 250 mcg IM every 15 min
          • Avoid in patients with asthma
    •  Trauma
      • Genital lacerations
      • Examine for tears in vaginal, cervical, and perineal areas under good lighting and suction
    •  Tissue
      • Retained placental tissue
      • Abnormally adherent placenta
      • May require manual exploration of uterine cavity with sterile gloves, removal of placental fragments
    • Thrombin
      • Reverse any coagulopathies

Hemorrhage in ESRD

• Uremic bleeding is a common consequence of chronic kidney disease which results in significant morbidity and mortality.²⁸ Uremic patients are at increased risk of bleeding for many reasons. Uremia is thought to result in toxin accumulation that disrupts von Willebrand Factor (vWF) leading to platelets’ inability to bind appropriately. Please refer to this previous emDocs post covering bleeding in the patient with renal failure for further insight into causes and recognition of uremic bleeding.
• While dialysis itself will help in the setting of uremic bleeding, this is unlikely to be a feasible intervention in the setting of massive transfusion until stability is achieved. Listed below are treatment options and interventions for our bleeding uremic patients presenting emergently:
• If the bleeding is related to the patients dialysis access (fistula or shunt)
  • Start with direct pressure to the site of bleeding. This will often be small and no bigger than a few millimeters.
  • You may place a tourniquet above and below the dialysis access site to control bleeding. However this may result in thrombosis of the graft or fistula. Another option is to have an assistant hold pressure above and below the dialysis access as demonstrated here. However do not hesitate to use tourniquets if bleeding is severe and difficult to control. Fistula/graft thrombosis is much preferable to death from hemorrhage.
  • Also demonstrated in the above video is the placement of a figure of 8 suture. When using this approach to controlling bleeding from a dialysis access site it is important to use a non cutting needle.²⁹
  • When managing dialysis access associated bleeding, hemorrhage control with a tourniquet is the priority. Only after the bleeding is controlled should attempts be made to place a suture.
• Bleeding unrelated to dialysis access
  • Desmopressin/DDAVP
    • Desmopressin improves bleeding in uremic patients by mechanisms not fully understood. It likely increases the release of factor 8 vWF from the vascular endothelium and by doing so improves platelet aggregation.³⁰
    • Dose: 0.3 mcg/kg SC or IV but may be administered intranasally at 3 mcg/kg if IV access is unavailable.
  • Protamine
    • Heparin is frequently used during dialysis sessions and if mass transfusing a dialysis patient that has received dialysis within the last 90 minutes then protamine should be given. It is dosed at 1 mg of protamine for every 100 units of heparin given but the dose of heparin will likely be unknown. In these cases, 10-20 mg of protamine can be given.³¹
  • Transfusions
    • Platelet transfusion
      • Must be used in combination with other agents such as desmopressin and cryoprecipitate due to platelets being unable to congregate appropriately in the uremic environment.³²
    • Packed RBCs
      • When given it should be in combination with desmopressin, platelets and cryoprecipitate due to the patient uremia and baseline clotting facture dysfunction.³²
    • Decision to transfuse blood products is based on the clinical picture and typically only in cases of uncontrolled hemorrhage.

Hemorrhage in Hemophilia

• Hemophilia is a condition highlighted by deficiencies of factor VIII (hemophilia A) or factor IX (hemophilia B).³³
• Hemophilia C is a rare condition caused by deficiency of factor XI.³⁴
• Talk to the patient, they know their disease! Use the factor they take at home
• If the patient does not know their factor activity or if they are incapacitated, assume 0% activity!
• Severity of hemophilia is determined by percentage of factor activity³⁵
  • Mild – 5-40% factor activity
  • Moderate – 1-5% factor activity
  • Severe – < 1% factor activity
• Factor replacement – Hemophilia A³⁶
  • Every 1 U/kg of factor VIII increases factory activity by 2%
  • Use 25 U/kg factor VIII to achieve 50% correction
    • Used in cases of mild to moderate hemophilia A
  • Use 50 U/kg factor VIII to achieve 100% correction
    • For severe bleeding and severe hemophilia A
•  Factor replacement – Hemophilia B ³⁷
  • Every 1 U/kg factor IX increases factor activity by 1%
  • 50 U/kg to achieve 50% correction
    • Used for mild to moderate bleeding
  • 100 U/kg to achieve 100% correction
    • Used for severe bleeds
• Factor replacement – Hemophilia C ³⁴
  • Quantitative measures of factor XI activity do not predict bleeding tendency; some patients with very low levels do not experience excessive bleeding, and some patients with higher levels do.³⁴
  • If available a dose of factor XI concentrate may be given for severe bleeding or major surgery in patients with higher bleeding risk.³⁴
  • Use of recombinant factor VIIa may be considered in patients who have factor XI inhibitors or who are at high risk for developing them; this is a bypassing agent that activates the coagulation cascade at a point beyond the factor XI step.³⁴
• No Factor available?
  • Cryoprecipitate contains 80-100 units of Factor VIII per donor bag ³⁷
    • Useful in Hemophilia A only.
  • DDAVP³⁶
    • Recommended for acute bleeding in patients with mild Hemophilia A.
    • Increases Factor VIII by 3-5x
    • 3 mcg/kg/dose IV
  • FFP ³⁷
    • Useful in Hemophilia A.
    • Also useful in Hemophilia C
    • 1 unit of factor/mL of FFP.
  • Prothrombin Complex Concentrate³⁵
    • Contains Factors II, VII, IX, X.
    • Potential thrombogenic side effects.
  • TXA³⁹
    • 10 mg/kg IV or 25 mg/kg PO
•  Inhibitors^36,40
  • Patients may develop antibodies or inhibitors to exogenous factor.
  • Recombinant factor VIIa
    • Factor VIIa activates Factor X, bypassing Factor VIII and IX.
  • FEIBA (factor eight inhibitor bypassing agent)

Conclusion/Pearls and Pitfalls

• Resuscitate massive hemorrhage with blood products. Crystalloids may worsen coagulopathy and are associated with worse patient outcomes.
• Avoid reliance on lab testing in the initial phase of resuscitation of massive hemorrhage. When to initiate, and how much blood product to give should be based on the patient’s clinical picture.
• Place large bore IVs and large central catheters for blood administration. Avoid rapid transfusion systems through triple lumen central lines.
• Don’t forget the Calcium. Calcium should be administered with each round of MTP to prevent worsening coagulopathy and hemorrhage.
• TXA administration has shown promise in reducing mortality in adult trauma patients with massive hemorrhage.
• Review the specialized medications that will aid in successful resuscitation of postpartum hemorrhage related to uterine atony.
• Consider DDAVP in the management of massive hemorrhage in patients with end stage renal disease.
• When treating hemorrhaging patients with known hemophilia, assume 0% activity of their deficient factor, if their activity levels are unknown.