Massive Haemorrhage
Yolandi Ferreira
Definitions
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Loss of entire blood volume equivalent within 24hrs
Loss of 50% of blood volume within 3hrs
Continuing blood loss of 150ml/min
Continuing blood loss of 1.5ml/kg/min over 20 min
• Rapid blood loss leading to decompensation and circulatory failure
despite volume replacement and interventional treatment
Lethal triad: Bloody vicious cycle
Factors contributing to the Coagulopathy
of Trauma
Acidosis
• Decrease coagulation factor activity
thrombin generation
platelet aggregation
• Enhanced fibrinolysis via increased tPa and
depletion of plasma activator inhibitor-1
Factors contributing to the Coagulopathy
of Trauma
Hypothermia
• Platelet dysfunction
• Reduced clotting factor activity
Dilutional Coagulopathy
• Factor deficiency
• Thrombocytopenia
• Anaemia
Factors contributing to the Coagulopathy
of Trauma
Consumption of
• Platelets
• Fibrinogen
• Clotting factors
Crit Care Med 2008 Vol 36, No 7 (Suppl.)
Prevent Coagulopathy
The aim: Prevent the Coagulopathy
• Most Rx arm of the lethal triad
• Appropriate choices of resuscitation fluids
• The amounts and ratio of these products to
one another
• The timing of delivery of these products
• The use of adjuncts to resuscitation
(recombinant Factor VIIa)
So how do we do this
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Current ATLS protocol
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1:3 Rule
Replacement of each 1ml of blood lost with 3ml isotonic crystalloid
Adult Hypotensive pt calls for a rapid infusion of 2L of an isotonic crystalloid solution
Red cells are recommended for transient or initial non-responders
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Time is of the essence
Clarke et al found that the probability of death increases approximately 1% for each 3min spent in the emergency department in patients
with major injuries isolated to the abdomen.
J Trauma 2002;52:420-5
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Intra-osseous access, almost forgotten, has gained renewed attention in adults
Permissive Hypotension
• Allowing the BP of the patient who has the
risk of major ongoing bleeding to not return
to normal values,
• But to stabilise at values around 75% of
normal until surgical control of bleeding is
established
• Prevention of rebleeding syndrome
Permissive Hypotension:
When + When not
Select +/- 3% of trauma population
• Ruptured AAA
• Bleeding DU/GU
• Major vascular trauma to Non-compressible
vessel
• Ongoing Intra Abdominal Haemorrhage
• Cold-coagulopathic-acidotic patient where
temporising surgery is planned
Contra-indications
Use normal rules for Resuscitation:
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Haemodinamically stable patient
Prior to exclusion of Obstructive Shock
Compressible bleed from isolated / external wounds
Major head trauma
Pregnant and childhood –no data yet
Burns
Possible crush syndrome / prolonged entrapment
Criteria to achieve
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Perfusion not pressure
Urine output
Lactate < 5 mmol/l
Rousable patient
• Palpable radial pulse
• SBP +/- 80mmHg
Massive Transfusion
• Many trauma centres have their own protocols:
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i.) Massive blood loss with profound haemorrhage / hypovolemic shock
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Adult pts who require >10 U
ii.) Continued bleeding after transfusion of 5 u in 4hrs / 10u in 24hrs
Iii.) Prolonged PT, Depressed Fibrinogen => DIC
• Intended to: Rapid restore blood volume
Prevent coagulopathy
• Operation Iraqi Freedom offered new evidence supporting a more
balanced approach
• PRBC/FFP/Platelet ratio 1:1:1
Borgman et al
• Retrospective analysis in Iraq
• Pt >10 units of PRBC within 24hrs
Three groups:
• 1:8
1:2.5
1:1.4 (plasma:PRBC)
• 65%
34%
19% mortality
Massive Transfusion
What Rx is available
Table 2. Resuscitation Fluids in both Clinical and Experimental Use
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Isotonic crystalloids (lactate ringer)
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Hypertonic saline solution (7.5% saline)
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Artificial colloids (dextran, hydroxyethyl-starch)
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Isotonic crystalloids with hydroxyethyl (Voluven®,
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HAES-steril®, Hespan®, Hextend®)
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Hypertonic saline solution with hydroxyethyl-starch
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(HyperHES®)
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Hypertonic saline solution with dextran (7.5% saline and 6%
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dextran)
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Isotonic crystalloids (lactate ringer) with pentoxifylline
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Isotonic crystalloids with ethyl pyruvate
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Hypertonic saline solution with pentoxifylline
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Human colloids (plasma, albumin)
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Fresh whole blood (FWB)
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Packed red blood cells (PRBCs)
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Artificial blood (hemoglobin-based oxygen carriers,
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perfluorocarbons, Polyheme®)
Fraga et al J Emerg Med 2009 Apr 1
Crystalloids / Colloids:
• NO CONSENSUS
• Ringers Lactate better than Normal Saline
- based mainly on animal studies in 1960!
• Colloids: Does NOT decrease ARDS
- survival assessment studies grossly under
powered
- Some suggests even increased mortality
Evidence
• Cochrane Database Systemic Review
• Perel et al concluded:
‘as colloids are not associated with an improvement in survival, and as they
are more expensive than crystalloids, it is hard to see how their continued
use in these patients can be justified outside the context of randomised
clinical trails’
• Nolan concludes that as long as the appropriate volume is given, the type
of fluid may not be of importance since anaemia is much better tolerated
than hypovoleamia
• Regarding bleeding: Colloids may interfere with coagulation more directly
than crystalloids
Hypertonic Saline
• Improves haemodynamics
• Rapidly corrects BP
• Improves tissue perfusion
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as drawing fluid from oedematous endothelium enhances mircocirculatory flow
• Hypotensive patients with
Penetrating injuries or
Head injuries
=> IMPROVEMENT OF SURVIVAL with the use of
hypertonic saline/dextran has been described
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Wade et al J Trauma 1997;42:S61-5
Wade et al J Trauma 2003;54:S144-8
Blood Component therapy
Fresh Whole Blood
• Key question driving current resuscitation
research
• ‘What is the optimal resuscitation fluid for a
severely injured trauma patient?’
• Simplest answer: ‘Give the patient back the
fresh whole blood that he lost’
Reality more complex
• Modern experience with FWB is small
Animal studies:
• Restores myocardial function better than PRBC
• Best 24hr hypotensive resuscitation fluid
US Army survival benefit
• Analysis is ongoing
Problem: Cost
Safety
Mimic delivery of whole blood 1:1:1
Recombinant Factor VIIa (Novoseven)
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Topic of considerable debate
Boffard et al
SA based Prospective trial
Reduction of blood transfusions with administration of
Factor VIIa in BLUNT trauma patients
• No effect on mortality
Boffard, Riou, Warren et al J Trauma 2005; 59:8-15
May prolong the ‘golden hour’ of resuscitation
rFVIIa enhances platelet thrombin
generation
rFVIIa
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Considerable debate
Timing
Selection of patients
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Less effective in acidosis
Remains effective in all but most severely hypothermic settings
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Theoretical risk of thrombo-embolic events must be balanced against the more acute risk of
exsanguination
- Less than 0.05% of serious events in >480 000 doses given to pts with haemophilia
- >1000 pts with haemophilia no statistically significant difference in events vs placebo group
Current limitations: Storage 2’C - 8’C
Short t1/2
High cost
Require completion of ungoing trails
Other Emerging Technologies
Topical Sealants
• Use in cases in which conventional measures of bleeding control fail
• Local application of concentrated clotting factors
• Fibrin in WW II for spinal and cranial injuries
• Floseal –relatively new agent
• Combination of bovine gelatine granules mixed with a human
thrombin solution
• No randomized studies have been performed
HemCon
• Shellfish derivative (chitosan)
• Causes Ionic attraction of red cells to stick to tissue +
over injured vessels
• Issued to UK soldiers 1:4
• Highly effective
• Now in thinner dressings –easier to push in
• Shelf-life 2yrs
QuikClot
• Volcanic rock
• Acts as a sponge, rapidly absorbing fluid to produce coagulation and
a stable blood clot in the wound
• It is chemically inert and is not absorbed into the body
• Safe to stay in the wound as long as needed
• Produces heat- can create burns
• Manufacturers:
Powder: Effective and less heat
• Included in US Marine first aid kits and more limited basis by US
Army in Iraq and Afghanistan
• Shelf life +/- millennium!
Anti-fibrinolytics
• Potential to reduce blood loss
• Aprotinin, Tranexamic acid, Epsilon aminocaproic acid
• Aprotinin suspended by FDA 2007 as result of reports of
increased mortality in CABG
• Increased renal and vascular complications and death
• No evidence to support the prophylactic or empiric use of
anti-fibrinolytics
• Major ongoing international trail CRASH-2
Artificial Hb-based O2 carriers
• Artificial Blood acts as O2 bridge
• Two classesof Hb substitutes:
Modified Hb
- Hemopure
Perfluorocarbons
• Red cell membranes are removed from out-dated red
cells
• Hb molecules are cross-linked to prolong shelf-life
• Phase III testing of Hemopure and Polyheme
Artificial blood
Advantages
• Immediate availability
• No need for x-match
• O2 carrying capacity
• Storage at room temperature
• Reduced risk of infectious,
immunological and metabolic
complications
Disadvantages
• Short half life 24 – 48 hrs
• Interference with laboratory
measures
• Lack of knowledge about
toxicity
The Mission
• For civilian providers the casualty is the
mission
• For the military medic, the mission must often
continue despite casualties
• Warfare has historically resulted in significant
advances in surgery and medicine
• Iraq and Afghanistan is no exception
Military Medicine:
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Rapid Identification, Rapid transfer
Massive transfusion: Recommend Ratio 1:1:1
Use of FWB advantages
Minimization of Crystalloid infusion
rFVIIa and other adjuncts
Hypothermia: Aggressive prevention and treatment
<C>ABC in Battlefield ATLS
References:
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An approach to transfusion and hemmorrhage in trauma: current prospectives on restrictive transfusion
strategies.
Tien H et al Can J Surg. 2007 Jun;50(3):202-9
Prehospital advances in management of severe penetrating trauma.
Robert Mabray Crit Care Med 2008 Jul;36(7 Suppl)S258-66
Exsanguination in trauma: A review of diagnostic and treatment options
Geeraedts et al Injury 2009 Jan;40(1):11-20 Epub 2009 Jan 8
The cellular basis of traumatic bleeding
Hoffman M. Mil Med. 2004 Dec;196(12Suppl):5-7,4
Monitoring of Hemostasis in combat trauma patients
Carr ME Jr. Mil Med. 2004 Dec;169(12 Suppl):11-5,4
Massive transfusion and nonsurgical hemostatic agents
Perkins JG et al Crit Care Med 2008 Jul;36(7 Suppl):S325-39
Warm fresh whole blood transfusion for severe hemorrhage
Spinella PC Crit Care Med 2008 Jul;36(7 Suppl):S340-5
Damage control resuscitation: a sensible approach to the exsanguinating surgical patient
Beekley AC Crit Care Med 2008 Jul;36(7 Suppl):S267-74
Are we giving enough coagulation factors during major trauma resuscitation?
Ho AM et al. Am J Surg. 2005 Sep;190(3):479-84
References:
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Transfusion practice in military trauma.
Hess JR Transfus Med. 2008 Jun;18(3):143-50
Are we giving enough coagulation factors during major trauma resuscitation?
Anthony M Am J of Surg 2005 190:479-484
Transfusion of Blood Products in trauma: an update
Fraga J of Emerg Med 2009.02.034
Effect of recombinant factor VIIa as an adjunctive therapy in damage control
Fox et al J Trauma 2009 Apr; 66(4 Suppl):S112-9
Talks:
Prof / Colonel Tim Hodgets
<C>ABC
Emergency Medicine in the developing world, Cape Town 2007
Tim Hardcastle
Fluids in Pre-hospital cases
Emergency Medicine in the developing world, Cape Town 2007