Covers an important topic for post graduate students

1. DAMAGE CONTROL
RESUSCITATION
PRESENTER: Dr Shreyas

4. Background
Uncontrolled hemorrhage: 40 % deaths in trauma patients
Physical hemostatic approaches
Coagulopathy: Resuscitation-induced phenomenon

5. Coagulopathy
• “Resuscitation-associated coagulopathy”
• LethalTriad: “vicious cycle of trauma” or the “bloody vicious cycle”
• Trauma induced coagulopathy

6. *Bad blood: A coagulopathy associated with trauma and massive transfusion review:Tawnya Vernon, Madison Morgan, and Chet Morrison Acute
Medicine & Surgery 2019; 6: 215–222

7. Resuscitation-associated coagulopathy
• Large amounts of fluids and blood products hypothermia
• Hypothermia platelet dysfunction and reduced enzyme activities
• Inadequate tissue perfusion anaerobic metabolism lactic
acid
• 0.9% normal saline
• Reduced activity of most of the coagulation factors with acidosis( Factor
VIIa ,Xa,Va)

8. LethalTriad
• In 1982, Kashuk and his colleagues emphasized the importance of
coagulopathy in their clinical review of 161 patients with major abdominal
vascular injury
• Downward spiral : further deteriorates hemorrhage
Kashuk JL, Moore EE, Millikan JS, Moore JB. Major abdominal vascular trauma--a
unified approach. J Trauma. 1982;22(8):672‐679. doi:10.1097/00005373-198208000-
00004

9. Trauma Induced Coagulopathy
• TIC/ATC
• Occurs prior to significant dilution , within 30 min of injury, and affects a
25% of the patients with severe trauma
• Higher mortality
• Dysregulation of the thrombomodulin–protein C system and is directly
related to injury, trauma, and shock

10. Trauma Induced Coagulopathy
• Presents as increased coagulation activation, coagulation impairment, and
increased fibrinolysis
• In fibrinolysis, tPA and the precursor plasminogen bind to fibrin, leading tPA
to activate and turn plasminogen into plasmin.
• Plasmin then cuts the fibrin and rapidly degrades the clot
• Hyperfibrinolysis is often seen in trauma patients, and historically is a 60–
100% predictor of mortality in trauma patients

12. Midwinter MJ, Woolley T. Resuscitation and coagulation in the severely injured trauma
patient. Philos Trans R Soc Lond B Biol Sci. 2011;366(1562):192‐203. doi:10.1098/rstb.2010.0220

13. Damage Control Resuscitation
• Balanced resuscitation
• Haemostatic resuscitation
• Rewarming
• Reversing acidosis
• Tranexamic acid
• Fibrinogen concentrates
• Prothrombin complex concentrate
• Cryoprecipitate
• Calcium
• Massive transfusion protocol

14. Balanced Resuscitation
• “Injection of a fluid that will increase blood pressure has dangers in itself. … If
the pressure is raised before the surgeon is ready to check any bleeding that
might take place, blood that is sorely needed may be lost”
—Walter Cannon. JAMA 1918;70(9): 620
• Aggressive crystalloid-based resuscitation
• cardiac and pulmonary complications
• gastrointestinal dysfunction
• coagulation disturbances
• disorders of immunological and inflammatory mediators

15. Balanced Resuscitation
• Its 3 basic tenets are
• Permissive hypotension
• Minimizing the use of crystalloid before surgical control of bleeding
• Transfusion of blood products in a ratio approximating whole blood
• Imbalances of intracellular and extracellular osmolarity that affect cell volume

16. Haemostatic resuscitation
• In 2007, Borgman and Holcomb et al. reported a survival benefit for the
high ratio of plasma to red blood cell (RBC) in patients who received massive
transfusions at a combat support hospital
• In the Japan-Observational study for Coagulation andThrombolysis in Early
Trauma (JOCTET), 189 severe trauma adult patients :They concluded that a
transfusion with an FFP/RBC ratio over 1.0 within the first 6 h reduces the
risk of death by about 60% in patients with blunt hemorrhagic trauma

17. Haemostatic resuscitation
• PROMMTT study (2013) Higher plasma and platelet ratios early in
resuscitation were associated with decreased mortality in patients who
received transfusions of at least 3 units of blood products during the first 24
hours after admission ( Survivor bias ?)
• The PROPPR trial (2015) found no statistically significant mortality
difference on the primary outcome of mortality between massive
transfusion protocols based on 1:1:1 and 2:1:1 ratios.There was an absolute
difference in mortality of about 4% favouring the 1:1:1 ratio, but the study
was not powered to detect this. A post-hoc secondary outcome of death
by exsanguination in the first 24 hours also favoured the 1:1:1 ratio.

18. Rewarming
• Passive warming measures
• insulting foil
• Blankets
• Removal of wet clothes
• The Initial fluid resuscitation- 40–42 °C
• Warming measures:
• Heated air inhalation,
• gastric or body cavity lavage with warmed fluids
• heat radiation
• Operating room should be raised, at best to a thermally neutral
• range (28–29 °C)

19. Reversing Acidosis
• Buffering of metabolic acidosis using drugs NOT RECOMMENDED
(aggravates the intracellular acidosis but also does not reverse the
coagulopathy)
• Fluid and blood resuscitation
• Vasopressor support
• Surgical control of hemorrhage
• Base deficit and lactate levels are the reliable indices with which to
evaluate the adequacy of the resuscitation and end-organ perfusion.

20. Tranexamic acid
• Antifibrinolytic agents
• CRASH-2: All-cause mortality and the risk of death due to bleeding were
significantly decreased with the administration of tranexamic acid. Maximal
beneficial effects were achieved if it was given within the first 3 h of injury
• MATTERs and MATTERs IITrials : Mortality was lowest in the TXA-plus
group (11.6%) andTXA-only group (18.2%) compared with the
cryoprecipitate-only group (21.4%), and neitherTXA nor cryoprecipitate
group (23.6%)

21. Tranexamic acid
• Mechanism of action
• Tranexamic acid is a synthetic derivative of lysine
• blocking lysine binding sites on plasminogen molecules, inhibiting the interaction of
plasminogen with formed plasmin and fibrin
• As a result, inhibition of plasminogen activation results in stabilization of the
preformed fibrin meshwork produced by secondary hemostasis
• Tranexamic acid when compared to similar compounds, namely ε-
aminocaproic acid, is six to ten times more potent in binding affinity to
plasminogen and plasmin
• Suppression of fibrinolysis, manifests as reductions in serum D-dimer
levels

22. Tranexamic acid
• Obstetrics:
• Abnormal Uterine bleeding
• Post Partum He
• Surgical Indications:
• Cardiothoracic
• Orthopaedic
• Dental procedures
• Haemoptysis
• Epistaxis
• Disorders of haemostasis:
• Haemophilia
• VonWillebrand Disease
• Hereditary angioedema
• Hereditary HemorrhagicTelangiectasia

23. Tranexamic acid
• Loading Dose: 1 gm in 100 mL saline infused over 10 minutes
• Maintainance dose: 1gm mixed in 500 mL saline infused over 8 hours
• Adverse effects: Hypotension, dizziness, allergic dermatitis, nausea,
vomiting, diarrhea, color changes, seizures (reported with high doses),
ureteral obstruction
• T1/2: 2-11 hours
• Excretion: Urine(> 95%)
• Contraindications:
• Allergy to tranexamic acid
• Defective color vision
• Acute vascular occlusive event

24. Don’t take a knife to a gun fight

25. Back to the Future
With Whole Blood ?

27. Types of Whole Blood
• Warm and Fresh
• Room temp (22C)
• Transfused within 8 hours
• Most military data
• Cold and Stored
• 2-6 C
• Stored for 14-35 days
• Civilian data

28. Volume and Concentrations Between
ComponentTherapy vs. Warm Whole Blood
Whole Blood: 500 mL
A singleWB unit
Red blood cell concentration: 38-50%
Platelets: 150,000-400,000
Coagulation factor : 100%
Component Therapy: 680 mL
RBC unit + PLT unit + FFP unit + Cryo
unit
Red blood cell concentration: 29%
Platelets: 80,000
Coagulation factors: 65%
VS

29. Standard Amounts of
Anti-coagulants and Additives in
Reconstituted Whole Blood vsWhole Blood
6 x RBC (AS-5) 6 x 120 ml = 720ml
6 x FFP 6 x 50 ml = 300ml
1 x aPLT 1 x 35 ml = 35ml
Total =1055ml
6 x 63ml = 378ml
Spinella PC, JTrauma. 2009;66:S69-76

30. Pros & Cons of Whole Blood
Advantages Disadvantages
1:1:1 ratio increase the risk of plasma-associated transfusion
reactions
Hct-35-50 % vs 29 % in Component therapy transfusion-transmitted disease
No throbocytopenia
Less risk of ABO incompatible transfusion
reactions than ABO compatible components
Less bacterial contamination risk
Logistical advantages
Less amount of additives / anticoagulants

31. Fibrinogen concentrates
• Fibrinogen has been reported to decrease more rapidly under critically low
concentrations than the other coagulation factors
• It bridges activated platelets and works as the key substrate of thrombin to
generate a stable fibrin mesh
• The effect of the administration of fibrinogen concentrates on outcome was
investigated by matched-pairs analysis using the GermanTrauma Registry.
Although 30-day mortality was comparable, 6-h mortality was
significantly lower in the patients receiving fibrinogen.

32. Prothrombin complex concentrate
• PCC contains variable amounts of factors II,VII, IX, and X is used to correct
coagulopathy
• TEG/ROTEM
• The administration of fibrinogen concentrate alone or in combination with
prothrombin complex concentrate resulted in a significant improvement of
fibrin polymerization and shorter clotting time
Kashuk JL, Moore EE, Johnson JL, Haenel J,Wilson M, Moore JB, et al. Postinjury life threatening
coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? JTrauma. 2008;65(2):261–70.
discussion 270-1.

34. Cryoprecipitate
• In the countries, where administration of fibrinogen concentrates is not
approved in trauma patients, cryoprecipitate is the alternative treatment
option as a source of Fibrinogen
• Cryoprecipitate is the alternative treatment option as a source of fibrinogen
• There are no reports suggesting positive effects of cryoprecipitate
administration on the survival of exsanguinating trauma patients

35. Calcium
• Low levels of ionized calcium at admission are associated with increased
mortality and an increased requirement for massive transfusion
• Citrate
• An ionized calcium concentration of < 0.6–0.7 mmol/L could lead to
coagulation defects
• Recommendation:
• monitored periodically
• with every 10 units of transfusion, and it is recommended that a concentration of at
least 0.9 mmol/L be maintained
• Dose : 1gm iv Ca Cl2 or 2-3 gm iv Ca gluconate

36. MTP
• Def: defined as the transfusion of 10 or more units of PRBC within the first
24 h of injury
• Total blood volume is replaced within 24 hours
• 50% of total blood volume is replaced within 3 hours
• Rapid bleeding rate is documented or observed

37. MTP
• Protocol:
• Patient selection for activation
• Description of the staff
• Blood bank are informed
• Cooled packs of O negative RBCs, type AB FFP, and platelets will be pre-packed for
quick delivery
• A high-ratio pack is continually delivered each time blood is requested until the
protocol is deactivated
• Type-specific blood will be delivered as soon as the patient’s blood type is determined

39. MTP
• The MTP is bundled with the
• administration of calcium
• factorVIIa
• fibrinogen.
• The laboratory examination of coagulation-TEG
• Score for prediction of patients who require MTP
• TASH
• ABC
• TBSS

41. FactorVIIa/
NovoSeven
Description:
• VitaminK-dependent
glycoprotein consisting of
406 amino acid residues
• MW 50 K Dalton
Mech of Action:
• When complexed with
tissue factor can activate
coagulation Factor X to
Factor Xa, as well as
coagulation Factor IX to
Factor IXa
Pk/Pd
• t1/2 was 2.3 hours
• Vd-103 mL/kg
• Dose-50-70 mcg/Kg
Uses:
Congenital FactorVII
Deficiency
Acquired Hemophilia
Massive Hge

42. Remote DCR
• DCR applied in the pre-hospital setting
• Three major components
• stop (hyper)fibrinolysis, tranexamic acid
• support clot formation, fibrinogen concentrate
• increase thrombin generation, prothrombin complex concentrate

43. Changes of surgical strategy in DCR

44. Conclusions
• DCR strategy is the measure that directly addresses trauma-induced
coagulopathy
• Plasma to RBCs ratio, the method of achieving balanced resuscitation, and
the administration of other coagulation factors, are not completely resolved

45. References
• MizobataY. Damage control resuscitation: a practical approach for severely hemorrhagic patients and its effects
on trauma surgery. Journal of Intensive Care. 2017 Dec 1;5(1):4.
• Cantle PM, Cotton BA. Balanced resuscitation in trauma management. Surgical Clinics. 2017 Oct 1;97(5):999-1014.
• Midwinter MJ,Woolley T. Resuscitation and coagulation in the severely injured trauma patient. Philosophical
Transactions of the Royal Society B: Biological Sciences. 2011 Jan 27;366(1562):192-203.
• Boukerrouche A. Modern Trauma Care: Damage Control Surgery and Damage Control Resuscitation-Brief Report.
EC Emergency Medicine and Critical Care. 2020 Jan 3;4(2):01-4.
• Cai J, Ribkoff J, Olson S, RaghunathanV, Al‐Samkari H, DeLougheryTG, Shatzel JJ.The many roles of tranexamic
acid: An overview of the clinical indications forTXA in medical and surgical patients. European journal of
haematology. 2020 Feb;104(2):79-87.
• Weymouth W, Long B, Koyfman A, Winckler C. Whole blood in trauma: a review for emergency clinicians. The
Journal of emergency medicine. 2019 May 1;56(5):491-8.