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EDUCATION IN THE MANAGEMENT OF BLEEDING

A practical, evidence-based guide for front-line physicians on how to Treat the Bleed

7 KEY PARTS (7 Ts) OF THE MASSIVE HEMORRHAGE PROTOCOL

The massive hemorrhage protocol (MHP) is a clinical pathway that brings together the right patient, right team, and right interventions at the right time points. MHP has been shown to improve patient outcomes and must incorporate the best available evidence and practices. The components of MHP are best summarized in terms of 7 Ts: trigger, team, tranexamic acid, testing, transfusion, temperature, and termination.

The MHP is appropriately triggered when a patient is massively bleeding, requiring red blood cells (RBCs) AND other components, such as plasma and platelets. Do NOT call an MHP if you only need unmatched RBCs.

  • Definitions of massive hemorrhage (such as 10 units/24 hours or 6 units in 4 hours) often not useful for managing patients, as hopefully one wouldn’t wait 24 hours before saying an MHP is appropriate!
  • All centres must have an objective trigger, as clinical gestalt alone has poor sensitivity and specificity (~65%)

Picture1

  • MHP predictor scores have been published and usually include combinations of clinical parameters, laboratory results, and ultrasound findings as variables
    • Scores that use all 3 categories are the most predictive; however, laboratory results are not immediately available and may delay activation. Trauma Associated Severe Hemorrhage (TASH) and Traumatic Bleeding Severity Score (TBSS) are the most useful scores from this group
    • If ultrasound and a competent operator are available, ABC score can be used for trauma patients and performs moderately well
    • To trigger, must have ≥2 of the following:
        • Penetrating mechanism
        • Systolic blood pressure (SBP) ≤90 mmHg, heart rate (HR) ≥120 bpm
        • Positive Focused Assessment by Sonography in Trauma (FAST) ultrasound
    • If not, use Shock Index (HR/SBP generally >1); it is easy to use and performs moderately well
    • Alternatively, the Critical Administration Threshold (≥3 units of RBCs within 1 hour) is also a useful trigger
    • Future considerations:
      • Biomarkers
      • Computer decision support tools
      • Iterative assessments
      • Physiological measurements
  • Triggering process
    • Ideally, MHP should be a code and triggered with a single phone call to a hospital switchboard and then the message disseminated by switchboard to all relevant team members
    • Ideally, MHP should be an overhead code to ensure that all team members are alerted simultaneously
    • Alternatively, MHP may be triggered through computerized physician order entry (CPOE) followed by a phone alert/overhead page to relevant parties
    • Many centres also trigger via a verbal/telephone order to transfusion medicine

References:

  1. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  2. Pommerening MJ, Goodman MD, Holcomb JB, et al. Clinical Gestalt and the Prediction of Massive Transfusion After Trauma. Injury. 2015;46(5):807-813.
  3. Shih AW, Al Khan S, Wang AY, et al. Systematic Reviews of Scores and Predictors to Trigger Activation of Massive Transfusion Protocols. J Trauma Acute Care Surg. 2019;87(3):717-729.

Patient outcomes are dependent on the quality of care provided by a high-performing interdisciplinary team including: physicians in emergency medicine, trauma, anesthesia, hematology/transfusion medicine, critical care, obstetrics; nurses; laboratorians in core laboratory and transfusion medicine; respiratory therapists; patient support workers; and porters.

Picture1

  • The MHP team must have a leader
    • The plan should specify how the leader is designated
  • The MHP team should also ideally include other physicians/clinicians to assist with care, including nurses (one to chart and one to provide care), porter or runner, transfusion medicine technologist, core laboratory technologist, and respiratory therapist
  • MHP must clearly describe roles and responsibilities of team members:
    • The MHP leader orders initiation and termination of the MHP and leads resuscitations care
    • Nurses provide care (e.g., monitors, performs diagnostic phlebotomy, administers transfusions and medications)
    • Transfusion medicine lab medical laboratory technologist (MLT) performs compatibility testing and prepares and issues blood components
    • Lead lab and clinical communicators should be established to minimize duplicate orders and other confusion; check-ins should be done at specific time points and/or when significant events happen, such as a patient transfer
    • The core laboratory MLT performs and results tests; calls all critical results to the MHP bedside team
    • The porter or runner transports laboratory specimens and blood components
    • Central locating/switchboard connects relevant personnel
    • Other services (surgery, interventional radiology, endoscopy, etc.) may be consulted as necessary to control bleeding
  • Team members should receive training and optimally participate in drills/simulations
  • Team members should have access to reliable and mobile means of communication during MHP
  • Identify team members with easily identifiable signs and/or clothing (e.g., MHP leader, porter, charting nurse)
  • For centres where definitive bleeding control cannot be provided, arrange to move the patient ASAP to a tertiary care centre 

References:

  1. Ali J, Rizolo S, Pavenski K. The Surgical Critical Care Handbook. Chapter 12: The Coagulopathic Trauma Patient and Massive Transfusion Protocol. World Scientific Publishing Co Pte Ltd. 2016.
  2. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  3. Nunez TC, Young PP, Holcomb JB, et al. Creation, Implementation, and Maturation of a Massive Transfusion Protocol for the Exsanguinating Trauma Patient. J Trauma. 2010;68(6):1498-1505.
  4. Young PP, Cotton BA, Goodnough LT. Massive Transfusion Protocols for Patients With Substantial Hemorrhage. Transfus Med Rev. 2011;25(4):293-303.

Tranexamic acid (TXA) is an anti-fibrinolytic drug and should be administered as soon as possible.

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  • TXA has been shown to reduce the rate of bleeding and improve survival rates in acute hemorrhage (in the settings of trauma and postpartum hemorrhage)
    • TXA does not reduce death from gastrointestinal (GI) bleeding and should not be used to treat upper or lower GI bleeding
  • Every 15-minute delay in time to administration of TXA decreases survival benefit by 10%
  • The dosage and infusion rate should be determined by the local institution

Picture3a

  • Dosing options include:
    • 1-g bolus followed by a second 1-g bolus 1 hour later
    • 1-g bolus followed by 1 g-infusion over subsequent 8 hours
    • 2-g bolus up front (suggested in resource-challenged locations, for centres transferring patient out, or where quality audits have shown that the second gram is frequently missed)

None of these dosing options have been compared head-to-head

References:

  1. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  2. CRASH-2 Trial Collaborators; Shakur H, Roberts I, Bautista R, et al. Effects of Tranexamic Acid on Death, Vascular Occlusive Events, and Blood Transfusion in Trauma Patients With Significant Haemorrhage (CRASH-2): A Randomised, Placebo-Controlled Trial. Lancet. 2010;376(9734):23-32.
  3. Gayet-Ageron A, Prieto-Merino D, Ker K, et al. Effect of Treatment Delay on the Effectiveness and Safety of Antifibrinolytics in Acute Severe Haemorrhage: A Meta-Analysis of Individual Patient-Level Data From 40 138 Bleeding Patients. Lancet. 2018;391(10116):125-132.
  4. HALT-IT Trial Collaborators. Effects of a High-Dose 24-h Infusion of Tranexamic Acid on Death and Thromboembolic Events in Patients With Acute Gastrointestinal Bleeding (HALT-IT): An International Randomised, Double-Blind, Placebo-Controlled Trial. Lancet. 2020;395(10241):1927-1936.
  5. Morrison JJ, Dubose JJ, Rasmussen TE, et al. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg. 2012;147(2):113-119.
  6. Woman Trial Collaborators. Effect of Early Tranexamic Acid Administration on Mortality, Hysterectomy, and Other Morbidities in Women With Post-Partum Haemorrhage (WOMAN): An International, Randomised, Double-Blind, Placebo-Controlled Trial. Lancet. 2017;389(10084):2105-2116.

The patient should have blood testing upon initiation of the MHP and then repeated at least hourly thereafter.

  • Laboratory testing can help identify patients receiving oral anticoagulant therapy and in need of reversal, assess quality of resuscitation, and guide blood component administration
  • Blood component therapy is administered at a 2:1 ratio (RBC to plasma) and then switched to goal-directed as soon as practical
  • Recommended tests include hemoglobin and platelet count, coagulation tests, and markers of organ injury and/or shock
  • Occasionally, blood testing may need to be done more frequently, based on clinical situation

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  • Recommended blood test bundle includes:
    • ABO blood group, antibody screen, and ABO verification
    • Complete Blood Count (CBC), International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), fibrinogen, Arterial Blood Gas (ABG), ionized calcium, lactate, and electrolytes
      • Note: aPTT does not need to be repeated as long as first PTT is concordant with the baseline INR
    • If available, rotational thromboelastometry (ROTEM) or thromboelastography (TEG) may also be useful
  • Biochemical tests (e.g., potassium, calcium, and pH) may indicate potential complications from massive transfusion or inadequate resuscitation of the patient in hemorrhagic shock
  • Lactate measurements are predictive of mortality, although the role of serial measurements in improving patient outcomes has not been confirmed in clinical trials
  • Laboratory should call all critical results to the bedside team

Having access to the most up-to-date laboratory results allows for more effective resuscitation and may improve patient outcomes.

Ensure correct blood work is drawn at the beginning of MHP and repeated hourly.

Picture4b

References:

  1. Bawazeer M, Ahmed N, Izadi H, et al. Compliance With a Massive Transfusion Protocol (MTP) Impacts Patient Outcome. Injury. 2015;46(1):21-28.
  2. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  3. Chandler WL, Ferrell C, Trimble S, et al. Development of a Rapid Emergency Hemorrhage Panel. Transfusion. 2010;50(12):2547-2552.
  4. Young PP, Cotton BA, Goodnough LT. Massive Transfusion Protocols for Patients With Substantial Hemorrhage. Transfus Med Rev. 2011;25(4):293-303.

  • Start with 4 units of RBCs and then switch to transfusion at a ratio of 2:1 for RBCs and plasma, i.e., transfuse 1 unit of plasma for every 2 units of RBCs
  • Administer platelets and fibrinogen replacement as per patient laboratory results
  • Switch to goal-directed transfusion as soon as practically possible

Picture5Aim to maintain minimum lab-based resuscitation targets:

Targets

Hemoglobin >80 g/L

INR <1.8

Fibrinogen >1.5 g/L

Platelets >50 x109/L

Calcium >1.15 mM

Treatment

RBCs

Frozen Plasma (FP) or Prothrombin Complex Concentrates (PCCs)

Fibrinogen Concentrate (FC)

Platelets

Calcium

  • Recommended lab-based resuscitation targets:

Recommended Resuscitation Targets

Ontario Regional 2019 MHP

European 2019 Guideline

World Federation of Societies of Anaesthesiologists (WFSA) 2012 Guideline

Hemoglobin

>80 g/L

70-90 g/L

>80 g/L

INR

<1.8

<1.5

<1.5

Fibrinogen

>1.5 g/L

>1.5-2 g/L

>1.0 g/L

Platelets

>50 x109/L

>50 x109/L;

 >100 x109/L if ongoing bleeding and/or TBI

>75 x109/L;

 >100 x109/L if multiple high-energy trauma, CNS injury, and/or platelet function abnormality

Calcium

>1.15 mmol/L

>1.1 mmol/L

>1.13 mmol/L

Standard approach to blood component delivery is applicable to most large adult hospitals:

Blood Pack

Standard Approach

Modifications for Smaller Centres

Box 1

4 RBCs

4 RBCs

Box 2

4 RBCs, 4 FP

4 RBCs, 2000 IU PCCs, 4 g FC

Box 3

4 RBCs, 2 FP, 4 g FC

4 RBCs, 2000 IU PCCs, 4 g FC

 

PLTs should be transfused based on count (recent guidelines suggest this is preferable to empiric transfusion)

If no PLTs, order from Canadian Blood Services (CBS)

  • For smaller hospitals with limited blood inventory, consider
    • PCCs 2000 IU can be substituted for coagulation factor replacement (e.g., when no thawing device or no plasma stocked in inventory)
    • Fibrinogen replacement should be given concurrently with PCCs unless the fibrinogen level is known to be ≥1.5 g/L
    • Transfer patient promptly to a centre capable of definitive hemorrhage control
  • Pediatric institutions will require age- and weight-based MHP

Other transfusion considerations:

  • When patient’s blood group is unknown, transfuse group O Rh negative RBC to females under the age of 45 years and O Rh positive RBC to all other patients
  • When patient’s blood group is unknown, transfuse group AB plasma
  • Switch to patient’s group-specific RBC and plasma as soon as blood group is available
  • To avoid hypothermia, transfuse RBC and plasma through a blood warmer
  • To avoid inadvertent component wastage, blood components should be transported and stored in appropriate temperature-controlled, validated containers until ready to transfuse
  • Take care to perform required pre-transfusion check to avoid mistransfusion
    • This means that patients must have an identification bracelet with unique identifiers
    • This also means that patient’s unique identifiers should not be changed until after MHP has been completed
    • If available, use positive patient identification technology to perform pre-transfusion check
  • Return blood components to transfusion medicine lab if no longer necessary

Potential risks of transfusion should be discussed

  • Transfusion-associated circulatory overload (TACO)
  • Hyperkalemia
  • RBC alloimmunization in women of child-bearing potential, which may result in hemolytic disease of the fetus/newborn; counsel to undergo RBC antibody screening 6 weeks and/or 6 months after transfusion

References:

  1. Bouzat P, Ageron FX, Charbit J, et al. Modelling the Association Between Fibrinogen Concentration on Admission and Mortality in Patients With Massive Transfusion After Severe Trauma: An Analysis of a Large Regional Database. Scand J Trauma Resusc Emerg Med. 2018;26(1):55.
  2. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  3. Dzik WH, Blajchman MA, Fergusson D, et al. Clinical Review: Canadian National Advisory Committee on Blood and Blood Products--Massive Transfusion Consensus Conference 2011: Report of the Panel. Crit Care. 2011;15(6):242.
  4. Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma: The PROPPR Randomized Clinical Trial. JAMA. 2015;313(5):471-482.
  5. Mesar T, Larentzakis A, Dzik W, et al. Association Between Ratio of Fresh Frozen Plasma to Red Blood Cells During Massive Transfusion and Survival Among Patients Without Traumatic Injury. JAMA Surg. 2017;152(6):574-580.
  6. Nascimento B, Callum J, Tien H, et al. Effect of a Fixed-Ratio (1:1:1) Transfusion Protocol Versus Laboratory-Results-Guided Transfusion in Patients With Severe Trauma: A Randomized Feasibility Trial. CMAJ. 2013;185(12):E583-589.
  7. Rao S, Martin F. Guideline for Management of Massive Blood Loss in Trauma. Update in Anaesthesia. 2012;28(1):125-129.
  8. Spahn DR, Bouillon B, Cerny V, et al. The European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma: Fifth Edition. Crit Care. 2019;23(1):98.

Hypothermia is common in both traumatic injury and other patient populations with major bleeding (e.g., postpartum hemorrhage) and is associated with worse outcomes. Hypothermia causes patient discomfort and hypotension, and increases blood loss. 

Picture6

  • Temperature should be measured within 15 minutes of MHP initiation or hospital arrival and then at a minimum of every 30 minutes (or continuously, where available)
  • It is critical to patient survival that the patient is kept warm
    • Every 1°C drop in body temperature increases blood loss by 20%, in part due to impaired coagulation
    • Hypothermia is associated with increased mortality rates
    • Target temperature is ≥36º C

All patients should receive interventions to prevent hypothermia. Warming of patients improves their comfort and, even in the absence of a confirmed survival benefit, it should be a core part of every MHP.

Picture6a

  • Ensure removal of wet clothing and minimize exposure by avoiding contact with cold surfaces and keeping a warm environmental temperature
  • Warm your patient with warm blankets and air blankets (such as Bair Hugger air blankets) to prevent heat loss
  • In addition, use fluid warmers so that the crystalloids and blood are warmed before infusion 

References:

  1. Lester ELW, Fox EE, Holcomb JB, et al. The Impact of Hypothermia on Outcomes in Massively Transfused Patients. J Trauma Acute Care Surg. 2019;86(3):458-463.
  2. Perlman R, Callum J, Laflamme C, et al. A Recommended Early Goal-Directed Management Guideline for the Prevention of Hypothermia-Related Transfusion, Morbidity, and Mortality in Severely Injured Trauma Patients. Crit Care. 2016;20(1):107.
  3. Rajagopalan S, Mascha E, Na J, et al. The Effects of Mild Perioperative Hypothermia on Blood Loss and Transfusion Requirement. Anesthesiology. 2008;108(1):71-77.

Once bleeding is under control, terminate MHP.

Picture7

  • Termination process and criteria must be clear to all team members
    • Terminate protocol when hemostasis is achieved and patient is stabilized or when patient dies
    • Call transfusion medicine laboratory to terminate protocol
  • Transfer care to the most appropriate team
    • Complete charting and reconcile transfused components
    • Update patient’s family
    • Consider transporting patient to a higher acuity hospital if more intensive care is needed and/or definitive interventions are needed
  • Return all blood components and blood containers/coolers remaining at bedside to transfusion medicine laboratory
    • Blood components can be transfused up to 4 hours post-issue
    • Blood components issued and outside of a validated temperature controlled environment (i.e., blood cooler or fridge) for more than 1 hour (not cumulative) cannot return to inventory and will be discarded by the transfusion medicine lab; to ensure no wastage, portering should be contacted as soon as MHP stands down
  • Team debriefing
    • What went well and what can be done better next time
    • Improves compassion fatigue and promotes resiliency, enables quality improvement
  • Multidisciplinary review for quality assurance
    • Mortality and morbidity rounds – focusing on facts rather than “blame”
    • Others: trauma care committee, transfusion committee

Quality metrics should be tracked over all activations of the MHP.

  • Based on audits of blood component utilization:
    • Common errors made:
      • Starting right away with RBCs, FP, platelets in bleeding patients on the ward (for example, most GI bleeds can start with 2-4 RBCs and do not require other components)
      • Ordering 4 doses of platelets when clinicians are thinking of 4 units of platelets; correct terminology is “1 adult dose” = 4 units of whole blood–derived platelets = 1 unit of apheresis platelets
      • Not moving towards goal-directed therapy and sticking to ratio-based therapy, or focusing only on giving large amounts of RBCs
      • Not checking and/or replacing fibrinogen
      • Not getting a group and screen and overusing group O RBCs and AB plasma
        • Getting a group and screen post-transfusion of group O RBCs is still useful for determining the patient’s blood group

Example Set of Quality Metrics

  • Proportion of patients receiving tranexamic acid within 1 h of protocol activation
  • Proportion of patients in whom RBC transfusion is initiated within 15 min of protocol activation
  • Proportion of patients (of those requiring transfer for definitive care) with initiation of call for transfer within 60 min of protocol activation
  • Proportion of patients achieving temperature ≥36°C at termination of the protocol
  • Proportion of patients with hemoglobin levels maintained between 60 and 110 g/L during protocol activation, excluding certain pediatric populations (e.g., neonates) that may require higher hemoglobin values
  • Proportion of patients transitioned to group-specific RBCs and plasma within 90 min of arrival/onset of hemorrhage
  • Proportion of patients with appropriate activation (≥6 RBC units in first 24 h, >40 mL/kg per 24 h of RBCs in pediatric patients) or before this level in patients dying due to hemorrhage within 24 h
  • Proportion of patients without any blood component wastage (including plasma that is thawed and not used within the 5-day limit on another patient)

Regular simulations increases team building and non-technical skills in trauma

  • Can range from a table-top exercise to high fidelity in situ simulations
  • Consider having video recordings of lab and clinical areas to raise awareness of roles within the MHP

References:

  1. Barleycorn D, Lee GA. How Effective Is Trauma Simulation as an Educational Process for Healthcare Providers Within the Trauma Networks? A Systematic Review. Int Emerg Nurse. 2018;40:37-45.
  2. Callum JL, Yeh CH, Petrosoniak A, et al. A Regional Massive Hemorrhage Protocol Developed Through a Modified Delphi Technique. CMAJ Open. 2019;7(3):e546-561.
  3. Rao S, Martin F. Guideline for Management of Massive Blood Loss in Trauma. Update in Anaesthesia. 2012;28(1):125-129.
  4. Schmidt M, Haglund K. Debrief in Emergency Departments to Improve Compassion Fatigue and Promote Resiliency. J Trauma Nurse. 2017;24(5):317-322.
  5. Spahn DR, Bouillon B, Cerny V, et al. The European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma: Fifth Edition. Crit Care. 2019;23(1):98.
  6. Yazer MH, Spinella PC, Doyle L, et al. Transfusion of Uncrossmatched Group O Erythrocyte-containing Products Does Not Interfere With Most ABO Typings. Anesthesiology. 2020;132(3):525-534.

Asset 2

A practical, evidence-based guide for front-line physicians on how to treat acquired bleeding