Massive Haemorrhage

Yolandi Ferreira

Definitions• 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• Current ATLS protocol

• 1:3 RuleReplacement 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

• Time is of the essenceClarke 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

• 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-indicationsUse normal rules for Resuscitation:

• 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

• 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: • i.) Massive blood loss with profound haemorrhage / hypovolemic shock 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 24hrsThree groups:• 1:8 1:2.5 1:1.4 (plasma:PRBC)

• 65% 34% 19% mortality

Massive Transfusion

What Rx is availableTable 2. Resuscitation Fluids in both Clinical and Experimental Use• Isotonic crystalloids (lactate ringer)• Hypertonic saline solution (7.5% saline)• Artificial colloids (dextran, hydroxyethyl-starch)• Isotonic crystalloids with hydroxyethyl (Voluven®,• HAES-steril®, Hespan®, Hextend®)• Hypertonic saline solution with hydroxyethyl-starch• (HyperHES®)• Hypertonic saline solution with dextran (7.5% saline and 6%• dextran)• Isotonic crystalloids (lactate ringer) with pentoxifylline• Isotonic crystalloids with ethyl pyruvate• Hypertonic saline solution with pentoxifylline• Human colloids (plasma, albumin)• Fresh whole blood (FWB)• Packed red blood cells (PRBCs)• Artificial blood (hemoglobin-based oxygen carriers,• 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 • as drawing fluid from oedematous endothelium enhances mircocirculatory flow

• Hypotensive patients withPenetrating injuries orHead injuries=> IMPROVEMENT OF SURVIVAL with the use of

hypertonic saline/dextran has been described• 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 SafetyMimic delivery of whole blood 1:1:1

Recombinant Factor VIIa (Novoseven)

• 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 mortalityBoffard, Riou, Warren et al J Trauma 2005; 59:8-15

May prolong the ‘golden hour’ of resuscitation

rFVIIa enhances platelet thrombin generation

rFVIIa• Considerable debate• Timing• Selection of patients

• Less effective in acidosis• Remains effective in all but most severely hypothermic settings

• 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 - HemopurePerfluorocarbons

• 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 bloodAdvantages• 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:

• 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:• 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:• 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