1. Damage Control Resuscitation
John B. Holcomb, MD, FACS
Professor and Vice Chair of Surgery
University of Texas Health Science Center, Houston, TX

2. Nothing to Disclose

3. Texas Trauma Institute Houston, TX

4. Memorial Hermann-TMC and UT Health Trauma Volume - 2012
Update slide

5. May 2, 2013
In 2010, there were 5.1 million deaths from injuries — 10% of all deaths — and the total number of deaths from injuries was greater than the number from infection with HIV, tuberculosis, and malaria combined (3.8 million).
Overall, the number of deaths from injuries increased by 24% between 1990 and 2010.

6. Years of Potential Life Lost (YPLL) Before Age 65
Cause of Death YPLL Percent
All Causes , %
Unintentional Injury 199, %
Suicide 52, %
Homicide 48, %
Malignant Neoplasms 137, %
Heart Disease 107, %
Perinatal Period 75, %
Congenital Anomalies 43, %
Cerebrovascular 21, %
HIV , %
Liver Disease 21, %
All Others , %
31.7%
The National Center for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System. US Department of Health and Human Services, CDC; Available at: Accessed May 22, 2009.

7. UTHSC-Houston 1999-2008 Trauma admissions = 36,028 and 2394 deaths = 6
UTHSC-Houston Trauma admissions = 36,028 and 2394 deaths = 6.6% Early deaths (≤ 24 hrs) = 1398 or 58%
30 days = 97%
Deaths from day = 68/2394 = 3%

8. J Trauma 2012
, 4,596 battlefield fatalities were reviewed
87% (n = 4012) of all injury mortality occurred pre-MTF
24% (n = 976) were deemed potentially survivable (PS)
91% (n = 888) died from hemorrhage

9. Bottom Line Up Front
Crystalloid resuscitation increase blood loss, transfusion requirements and death
Balanced blood product resuscitation decreases blood loss, transfusion requirements and improves survival
Must have thawed/liquid plasma in the ED to really do this well
Time is critical

10. How to Resuscitate? Its not just raise the BP
Not just the hole in the blood vessel that needs rapid suture
Why do we give RBCs first?
Red stuff
Reverse the systemic and iatrogenic endothelial injury
Reverse permeability
Prevent edema
Repair the endothelium
Dampen the systemic inflammatory response
Prevent and Reverse coagulopathy
Time is important

11. Rapid progress in trauma care occurs during a war.
J Trauma, 2007.
Rapid progress in trauma care occurs during a war.
Damage control resuscitation addresses diagnosis and treatment of the entire lethal triad immediately upon admission.

12. DCR components Stop bleeding Hypotensive resuscitation
Minimize crystalloid
Use thawed plasma to resuscitate patients
Increased platelet use
Reverse hypothermia and acidosis
Hemostatic adjuncts

13. J Trauma 2012

14. Typical 24 hour Resuscitation
NOW
3-5 liters of LR
7 RBCs
6 FFP
1 platelets
THEN
20 liters of LR
15 RBCs
5 FFP
0 platelets
Associated with decreased edema, MOF and improved survival

15. 2004

16. 17 yr, GSW Liver, 60/30, BD-17 2010 11 RBC 10 FFP 2 platelet
3 liters crystalloid
3 ops
Home in 8 days
2010

17. Rt pulmonary lower lobe wedge, Rt hepatic lobectomy, Rt nephrectomy
14 RBC
14 FFP
2 platelets
2 cryo
2 liters
of crystalloid
2014

18. Post Operative Damage Control Laparotomy and Thoracotomy

19. 5 days post op Home day 10

20. Component Therapy Component Therapy: Hct 29% Plt 80K
1U PRBC + 1U PLT + 1U FFP + 1 U cryo
680 COLD mL
Hct 29%
Plt 80K
Coag factors 65% of initial concentration
WWB:
500 mL Warm
Hct: 38-50%
Plt: K
Coag: 100%
1000 mg Fibrinogen
Armand & Hess, Transfusion Med. Rev., 2003

21. Which one to use, start, how much, stop ??

22. Plasma and Platelets for everyone?
Dzik WH. Predicting hemorrhage using preoperative coagulation screening assays.
Curr Hematol Rep
Gajic O, Dzik WH, Toy P. Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intensive care unit: benefit or harm?
Crit Care Med
Abdel-Wahab OI, Healy B, Dzik WH. Effect of fresh-frozen plasma transfusion on PT and bleeding in patients with mild coagulation abnormalities.
Transfusion

23. J Trauma, 2007
, n = 252
P < 0.05
16231 53
162

24. Multicenter (16) Retrospective Massive Transfusion Study
Ann Surg 2008
Multicenter (16) Retrospective Massive Transfusion Study
12 months data collection
≈ 30,000 admissions and ≈11,650 transfused
466 MT’s

25. 30 day Kaplan-Meier

26. JACS 2010
12 hrs
24 hrs

27. Ann of Surg, 2011 vs

28. DCR in DCL: DCR patients received less, (p<0.05).
crystalloids (14 L vs. 5 L), RBC (13 U vs. 7 U),
plasma (11 U vs. 8 U) platelets (6 U vs. 0 U)
ALI, AKI, MOF all lower in DCR patients
24-hour and 30-day survival was higher in DCR
(88% vs. 97%, p=0.01 and 76% vs. 86%, p=0.03).
MTs in the DCL population decreased from 67% to 43% (p<0.01)
In severely injured patients who underwent DCL; DCR was associated with both decreased blood product use and improved survival.

29. However at UAB, they don’t give plasma early
J Trauma 2009
Very important paper, not only for this topic, but all uncontrolled studies
“They lived long enough to receive a treatment, not that the treatment caused them to live longer”
However at UAB, they don’t give plasma early
Median of 18 min vs 93 (RBC vs plasma administration)

30. How do you make early blood products happen?
Work with the Blood bank and Donor Center
O- RBCs—in the ED
AB or A plasma—in the ED
Thawed or Liquid plasma
Platelets—in the ED?
Prehospital?

31. Implementation of a ED-TP protocol:
JAMA Surg, 2013
Implementation of a ED-TP protocol:
Decreased time to first plasma transfusion (89 vs 43 minutes, p.= .001).
The TP-ED protocol was associated with a reduction in 24-hour transfusion of RBCs (p=.04), plasma (p=.04), and platelets (p=.001).
Logistic regression identified TP-ED as an independent predictor of decreased 30-day mortality (p=.04).

32. Overall mortality was 25%
JAMA Surg 2013
3.6% of admissions received a blood transfusion within 6 hours of admission
Overall mortality was 25%
94% of hemorrhagic deaths occurred within 24 hours
the median time to hemorrhagic death was 2.6 hours,
range, hours

33. Transfused = big mortality
There were 34,362 trauma admissions in 10 centers over 58 weeks
12,560 (36%) highest level activations
1245 (10%) were transfused within 6 hours
905 (7%) received a transfusion of ≥ 3 RBCs
25% mortality

34. PROMMTT plasma:RBC
Hem death at 2.6 hrs

35. PROMMTT platelets:RBCs
Hem death at 2.6 hrs

36. PROMMTT
Data suggest that earlier and higher ratios of plasma and platelets were associated with decreased in-hospital mortality in the first 6 hours.
1:1:1 is superior to 1:1:2

37. J Trauma, 2012
Injury severity same
Mortality improved

38. J Trauma 2013 TRALI (0) vs CRALI (505)?
The incremental amount of crystalloid
rather than the amount of blood
products transfused during the first day of care
seems to be the modifiable risk factor
for lung injury.
TRALI (0) vs CRALI (505)?

39. All the retrospective studies
Lots of
work
over a
long
time
Whole Blood vs Components Study
Frozen Blood vs Stored Blood
All funded
by DoD

40. J Trauma, 2011

41. J Trauma 2011
J Trauma 2012

42. R-TEG Graphical Display in the ED
We no longer send PT / PTT / INR, fibrinogen and platelet counts

43. UT Health Science Center and Memorial Hermann Hospital Houston, TX
Ann Surg 2012
UT Health Science Center and
Memorial Hermann Hospital
Houston, TX

44. Methods
Consecutive trauma patients (1974) admitted between Sept 2009 and Feb 2011 (18 months) who were the highest level trauma activations.
Demographics, vital signs, and ISS were recorded.
All had admission r-TEG and CCTs.
We correlated r-TEG values with their corresponding CCTs for transfusion requirements.
Charges were calculated for each test.

45. CCTs vs TEG Charges CCTs = $286 PT, aPTT, INR Platelet count
3 ml single tube
CCTs = $286
PT, aPTT, INR
Platelet count
Fibrinogen level
D-dimer = $251
9 ml in two tubes

46. Results When controlling for age, injury mechanism, w-RTS, BE and Hgb
ACT predicted RBC transfusion and the -angle predicted MT better than PT/aPTT or INR (p < 0.001)
The -angle was superior to fibrinogen for predicting plasma transfusion (p < 0.001)
MA was superior to platelet count for predicting platelet transfusion (p < 0.001)
LY-30 documented fibrinolysis.
These correlations improved for transfused, shocked or head injured patients.

47. Summary
Considering the speed, charges, and global functional information obtained, TEG is superior to CCTs.
acute care surgery group, emergency medicine, orthopaedics, anesthesia, neurosurgery, pediatric surgery

48. How we use TEG

49. 2005-2011, 1412 (4.7%) patients sustained blunt liver injury.
AAST Grade IV and V injuries accounted for 244 (17%) patients, of which 206 patients survived to leave the ED.
Pre DCR vs DCR
The DCR cohort had an increase in successful non-operative management
54 to 74%, p<0.01
The DCR treatment cohort resulted in improved survival
73% to 94% (p<0.01).

50. Survival of Grade 4 and 5 Liver Injury over 7 years n = 206

51. How does plasma “work”? Is it all the same?
Replace lost or consumed coagulation proteins?
Stabilize the endothelium?
Just a better colloid?
Need some mechanistic work here

52. J Trauma 2010
It is possible that the thousands of proteins in FFP promote vascular stability through regulation of critical junction proteins.
Compromise of EC junctions could lead to a number of deleterious effects:
barrier dysfunction, interstitial edema, tissue hypoxia, inflammatory cell infiltration, detached pericytes, extracellular matrix breakdown, apoptosis and exposed subendothelium.
We suggest a possible beneficial effect of FFP on hemostasis at the EC level,
as opposed to the traditional view of FFP as only a source of clotting factors.

53. Pulmonary Endothelial Cell Permeability
Findings:
Plasma and LP are both Protective against EC permeability
LR has no protective effects on EC permeability
3. The protective effects of plasma diminish with time
J Trauma, 2010

54. Anes & Analg, 2011
The glycocalyx is a ubiquitous barrier that protects the underlying endothelium and prevents injurious neutrophil-endothelial interaction.
A = baseline
B= shock
C = LR resus
C = Plasma resus C A B D

55. Shock 2012
NS Hextend FFP

56. Stem Cells and Dev 2011

58. Prehospital and Hospital
No distinction
Should be a seemless continuum
What works in the hospital should be used prehospital

59. Ann Surg 2013

60. RBC and FFP on Helicopters
19 months
4 helicopters
2 units O- and 2 units thawed AB plasma
Indications for transfusion same as in the ED
150 trauma patients
90% continued receiving products in the ED
Improved early survival

61. Back to the Future Lyophilized Plasma Resuscitation

62. Dried Plasma in the IDF

63. Shock, 2013

64. Dried Plasma Product Carried by US Special Operations Forces

65. Different ProCoagulants
Kcentra is available as a single-use vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S as a lyophilized concentrate
Many US Companies
Working on
dried plasma

66. So what do we do - today Identify patients who need resuscitation
Prehospital and hospital
Use blood products, not crystalloid or artificial colloids
Transfuse in a balanced fashion, starting with the first units
Platelets early
When the rate of transfusion slows, transition to TEG driven

67. Concept Not rigidly ratio driven Not rigidly TEG (or ROTEM) driven
Incorporates the elements of time and logistics and personnel specific to our site
Plasma is our primary resuscitation fluid

68. Summary Uncontrolled Hemorrhage is a major problem
Limit crystalloid, use more plasma and platelets
Predictive models are here
Must start components earlier
Place blood products in the ED
Do the preclinical and human studies
Improved study design and analysis
Mechanistic studies will allow more focused tx