A talk from The Big Sick conference in Zermatt, 2018. All talks: https://scanfoam.org/tbs18 and https://scancrit.com

1. TRAUMA HEMOSTASIS AND
OXYGENATION RESEARCH NETWORK
ZERMATT FEBRUARY 2018
RDCR.org
GEIR STRANDENES, MD
CHRISTOPHER BJERKVIG MD

3. HEMORRHAGIC SHOCK
PHYSIOLOGYAND OXYGEN DEBT-
RATIONALE FOR PRESHOSPITAL BLOOD
TRANSFUSION – THE HOLISTIC VIEW
«disce quasi semper victurus quasi cras moriturus

4. REMOTE DAMAGE CONTROL RESUSCITATION
(FOR BLOOD FAILURE)-RDCR
RDCR.org
BLOOD FAR FORWARD FOR BLOOD FAILURE – BFFFBF
Geir Strandenes, MD
Senior Anesthetist
Dept of War Surgery and Emergency Medicine
Norwegian Armed Forces Medical Services
Co-Chair Thor Network
Dept.of Immunology and Transfusion Medicine
Haukeland University Hospital

5. Blood Far Forward For Blood Failure
BFFFB
“There are three stages of scientific discovery: first
people deny it is true; then they deny it is
important; finally they credit the wrong person.’’
Alexander von Humboldt (1769-1859)

7. GOAL : Improve survival of patients with life
threatening bleeding : focus on the
presurgical phase of care

8. Research group in Bergen
Blood Far Forward (BFF)

9. Tverrfaglig
Laboratoriefolk
Laboratorieleger
Klinikere
Gruppen
Turid Helen
Biokjemiker
Hanne
Bioingeniør
Joar
Bioingeniør
Christopher
Anestesilege
Theodor
Anestesilege
Torunn
Lablege
Einar
Lablege
Tor
Lablege
Håkon
Medisinstud.

10. THOR- Trauma Hemostasis & Oxygenation
Research Network
An international multidisciplinary network of
civilian and military providers ranging from
first responders and medics to critical care
physicians and from basic scientists to
clinical trialists.

11. Advocates for:
• FWB or CWB as the optimal prehospital choice for hem. shock
• TXA as an adjunct to whole blood
• Balanced blood components if FWB not feasible

12. DISCLAIMER
The opinions or assertions contained herein are the private views of the author and are not to be
regarded as official nor as reflecting the views of UiB or Norwegian Armed Forces Medical Service.
This presentation includes studies that were conducted under protocols reviewed and approved by
the Regional committee for medical and health research ethics and performed in accordance with
the approved protocol.

13. LETS FOCUS ON OXYGEN (GAS OF LIFE)
Oxygenation
D02 = 1.34 x Hgb x Sa02 x CO
RDCR.org

14. "Everything that needs to be
said has already been said. But
since no one was listening,
everything must be said again."
André Gide

15. Fluid Resuscitation from
Hemorrhagic Shock: 2014
“The historic role of crystalloid and colloid solutions in
trauma resuscitation represents the triumph of hope
and wishful thinking over physiology and experience.”
LTC Andre Cap
J Trauma, 2015
There is an increasing awareness that fluid resuscitation
for casualties in hemorrhagic shock is best
accomplished with fluid that is identical to that lost by
the casualty - whole blood.

16. «The transfusion of whole blood – A suggestion for
its more frequent employment in war surgery»
«But the addition of salt solution to the circulation is
at best only a temporary measure, and merely
makes up for the loss of fluid, which is only one
factor in the condition»
«The broad indications for blood transfusion are
based on the fact that transfused blood is the best
substitute for blood lost (…) In certain haemorrhages
it has definitive haemostatic properties (…)

17. Experience matters??
WORLD WAR 2

18. Experience matters??
KOREA

19. Experience matters??
VIETNAM

20. Experience matters??
THE CRYSTRALLOID
ERA

21. A Paradigm Shift
• How did we get here ?

22. HISTORICAL CHANGE IN APPROACH
• WHOLE BLOOD INTRODUCED AS FLUID OF CHOICE WW1 –
NO RANDOMISED CONTROL TRIAL(RCT)
• PENICILLIN SAVED THOUSANDS OF LIFES DURING WW2 –
NO RCT
• FREEZE DRIED PLASMA INTRODUCED WW2 – 10 MILLION
UNITS USED – NO RCT
• COMPONENTS INTRODUSED – NO RCT
• CRYSTALLOIDS INTRODUCED – NO RCT
• BLOOD REINTRODUCED – NO RCT

23. HISTORICAL CHANGE IN APPROACH
• MURPHY AND GARDNER CHANGED PLATELET TRANSFUSION
STRATEGY BASED ON IN VITRO STUDIES AND IN VIVO
RECOVERY AND SURVIVAL DATA
• COLD STORED PLATELETS HAVE BETTER PRESERVED
MITOCHONDRIAL RESPIRATION AND AGGREGATION
• WE STILL USE RT STORED PLT FOR BLEEDING
• ONE RANDOMISED CONTROLED CLINICAL TRIAL

24. COLD PLATELETS RANDOMISED TRIAL

25. WILL THIS GO INTO THE MEDICAL HISTORY BOOKS AS
THE TRANSFUSION MADNESS??
Fresh Milk stored on the kitchen table for 7 days!

26. "EVIDENCE DOES NOT DRIVE
ADVANCES IN TRAUMA CARE.
PEOPLE DO THAT"
Frank Butler, M.D.
CAPT MC USN (Retired)
Chairman
Committee on Tactical Combat Casualty Care
Joint Trauma System
Chief
Prehospital Trauma Care
Joint Trauma System

27. RDCR FOR BLOOD FAILURE
1. YOU MIGHT HAVE A DIFFERENT OPINION
2. BUT YOU CANT HAVE A DIFFERENT
PHYSIOLOGY
RDCR.org

28. Guidelines
Civilian guidelines
• Use of isotonic crystalloid solutions should be
initiated in the hypotensive bleeding trauma
patient.
• RBC treatment should aim to achieve a target
Hb of 7-9 g/dl
• Initial management of patients with expected
massive haemorrhage should include plasma in a
plasma- RBC ratio of at least 1:2 as needed or
fibrinogen concentrate and RBC according to Hb
level.
• Platelets should be administered to
maintain a platelet count >50 109/l. A
platelet count >100 109/l in patients with ongoing
bleeding and/or TBI may be maintained.
• If a concentrate-based strategy is used, fibrinogen
concentrate or cryoprecipitate should be
administered if significant bleeding is accompanied
by viscoelastic signs of a functional fibrinogen
deficit or a plasma fibrinogen level of less than 1.5-
2.0 g/l.
Military guidelines (TCCC)
1) Whole Blood (Hb 12-13G/DL)
2) Plasma RBC’s Platelets (1 : 1 : 1) (Hb 9,0 gr/dl)
3) Plasma RBC’s (1 : 1)
4) Plasma or RBC’s alone
5) Colloids and crystalloids only if above is not
available

29. Traumatic hemorrhagic shock?
You need a surgeon ASAP!
Problem: You don’t have one!

30. Remote
Prehospital (or
far-forward/
austere) phase
of resuscitation

31. + Damage Control
Damage Control:
First, only do the things
essential to keeping the ship
afloat.
Rotondo MF, Schwab CW, et al. J Trauma. 1993;35(3):375-82.

32. + Resuscitation
Emergency treatment to restore:
Circulating volume
Aid oxygen delivery
Replace hemostatic potential
(and a few
other things…)

33. RDCR-WHAT ARE WE AIMING FOR??
• Maintain Oxygen Delivery(D02) above the threshold for delivery
dependent oxygen consumption(V02)
• Maintain/Support hemostasis to reduce the “Blood Leak”
• No shock – no coagulopathy!
• Prevent shock or treat shock??
RDCR.org

34. Blood Failure
RBC Failure
Shock (oxygen debt)
Hemostatic System Failure
Bleeding/Thrombosis
Endothelial Failure
Capillary leak
Hemostatic dysfunction
Immune Failure
Infection
Thrombosis
Bjerkvig CK, Strandenes G et al. Transfusion. 2016
White NJ, Ward KR et al. J Trauma 2017
Spinella PC, Cap AP. Curr Opin Hematol. 2017.

35. BLOOD AS AN ORGAN
RDCR.org
Understand shock,
endotheliopathy, and coagulopathy not
as isolated events, but rather as the
result of changes
taking place within a single dynamic
organ system

36. Shock & Coagulopathy: 2 sides of the
same coin (blood failure)
Blood loss  hypoxia
Hypoxia  fibrinolysis/coagulopathy
Coagulopathy  Blood loss…
Must treat shock & coagulopathy
simultaneously:
Functionality of WHOLE BLOOD
Schwameis CCM 2015.

38. SHOCK IS BAD FOR YOU!!
RDCR.org

39. Level of shock is correlated with
outcome
• Manikis, Panagiotis, et al. "Correlation of serial blood lactate
levels to organ failure and mortality after trauma." The
American journal of emergency medicine 13.6 (1995):
• Husain, Farah A., et al. "Serum lactate and base deficit as
predictors of mortality and morbidity." The American journal
of surgery 185.5 (2003): 485-491.
• Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM,
Peguet O, et al. Earlycoagulopathy in trauma patients: an on-
scene and hospital admission study. Injury2012;43:26-32
RDCR.org

40. Level of shock – correlated with level
of coagulopathy and inflammation
Brohi K, Singh J, Heron M, et al. Acute traumatic coagulopathy. J
Trauma 2003; 54:1127–1130
Macleod JBA, Lynn M, McKenney MG, et al. Early coagulopathy
predicts mortality in trauma. J Trauma 2003; 55:39–44
Maegele M, Lefering R, Yucel N, et al. Early coagulopathy in multiple
injury: an analysis from the German Trauma Registry on 8724
patients. Injury 2007; 38:298 – 304
Hess et al, J Trauma 2008 (ACOTS)

41. Hypoperfusion and shock(OXYGEN DEBT) is
probably the primary initiator of
coagulopathy (ACoT)
Brohi K, Cohen MJ, Ganter MT, et al. Acute traumatic coagulopathy: initiated
by hypoperfusion: modulated through the protein C pathway? Ann Surg
2007; 245:812–818
Blood doesn’t coagulate
“Blood failure”

42. Compensation/consequences of
decreased DO2 (due to bleeding)
D02 = Hgb x Sa02 x CO
Tachycardia
Weak/absent pulses
Cold, clammy
Increased RR, due to lactacidosis
Urine output
Slow mentation

43. Poiseuilles law
BP=CO x SVR

44. Anestesi

45. PERMISSIVE HYPOTENSION:
“PRESERVING COAGULATION, REDUCING
BLEEDING WHILE SACRIFISING PERFUSION”

46. RED CELLS MATTER!
REPRESENTS THE BULK OF THE CLOT
RDCR.org

47. RED CELLS MATTER!
CARRIES OXYGEN!
RDCR.org

48. RED CELLS MATTER!
DON’T FORGET PLATELET ADHESION
RDCR.org

49. Brit. -1. Haemat., 1961, 7, 42.
The Role of Red Cells in Haemostasis: the Relation between
Haematocrit, Bleeding Time and Platelet Adhesiveness
ARVIQ J. HELLEM, CHR. F. BORCHGREVINK AND SARA BETH AMES*t
Institutefor Thrombosis Research, University Hospital, Rikshospitalett
The Effect of Hematocrit on Platelet Adhesion: Experiments and
Simulations.
Spann AP, Campbell JE, Fitzgibbon SR, Rodriguez A, Cap AP, Blackbourne
LH, Shaqfeh ESG.
Biophys J. 2016 Aug 9;111(3):577-588
RDCR.org

50. THE PERMISSIVE HYPOTENSIVE
APPROACH = LOW FLOW STATE
• CO 3,0/MIN, Hb 14gr/dl, sp02 98% D02=551 ml/min
• CO 3,0l/min, Hb 7gr/dl, Sp02 98% D02=275 ml/min
• Maximum obtainable V02 Hb 14 = 385ml/min(above threshold)
• Maximum obtainable V02 Hb 7 = 192ml/min (below treshold)
RDCR.org

51. • Not a treatment
• Necessary evil??
• Evidence????
Bicknell WH, Wall MJ, Pepe PE, Martin RR, Ginger VF, Allen MK, et al. Immediate versus delayed fluid resuscitation for hypotensive
patients with penetrating torso injuries. N Engl J Med 1994;331:1105-9
Turner J, Nicholl J, Webber L, Cox H, Dixon S, Yates D. A randomised controlled trial of prehospital intravenous fluid replacement therapy
in serious trauma. Health Technology Assessment 2000;4:1-57.
Dutton RP, Mackenzie CF, Scalae TM. Hypotensive resuscitation during active haemorrhage: impact on hospital mortality. J Trauma
2002;52:1141-6.
SAFE Study Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group; Australian Red Cross Blood Service;
George Institute for International Health, Myburgh J, Cooper DJ, et al. Saline or albumin for fluid resuscitation in patients with traumatic
brain injury. N Engl J Med 2007;357:874-84

52. What about delayed evacuation?

53. How long in the low-flow state??
Evidence?
• Garner, Jeff, et al. "Prolonged permissive hypotensive
resuscitation is associated with poor outcome in primary blast
injury with controlled hemorrhage." Annals of surgery 251.6
(2010): 1131-1139.
– 30% Bloodloss – SBP 80mmHg – Mean survival - 2 h
• Doran, Catherine M., et al. "Targeted resuscitation improves
coagulation and outcome." Journal of Trauma and Acute Care
Surgery 72.4 (2012): 835-843.
– 35% Bloodloss – SBP 80mmHg vs 110mmHg – Mean survival
hypotensive group - 3 h
– Significantly shorter survival in the hypotensive group
• Skarda DE, Mulier KE, George ME, Beilman GJ. Eight hours of
hypotensive versus normotensive resuscitation in a porcine
model of controlled hemorrhagic shock. Acad Emerg Med
2008;15:845– 52.
– 35% Bloodloss SBP 65 vs 80 vs 90mmHg
• Increased mortality and persistent BD and low StO2

54. DO2
Time
D02 = 1.34 x Hgb x Sa02 x CO
Critical DO2
Aerobic metabolism
Dose of shock
POI Active bleeding
DO2 falling
Compensation
Shock
Resuscitation
Anaerobic metabolism

55. Hypotension is 100 mm Hg on the battlefield
Brian J. Eastridge, M.D.*, Jose Salinas, Ph.D., Charles E. Wade, Ph.D.,
Lorne H. Blackbourne, M.D.
RDCR.org

56. Hypotension is 100 mm Hg on the battlefield
Brian J. Eastridge, M.D.*, Jose Salinas, Ph.D., Charles E. Wade, Ph.D.,
Lorne H. Blackbourne, M.D.
RDCR.org

57. THE LAST 2 SLIDES EXPLAIN
IF SYST BP IS BELOW 100mmHG UPON ARRIVAL
YOU HAVE GAINED OXYGEN DEBT = SHOCK
RDCR.org

58. Kotwal, RS; Howard, JT; Orman, JA et. al. The effect of a golden hour policy on the morbidity and mortality of combat casualties. JAMA
Surgery. 2016;151(1):15-24.
Key Findings:
1. Case Fatality Rate decreased significantly after mandate
2. Median transport times decreased by more than half after
mandate
3. Individual patients with ISS ≥ 25 (Critically Injured) transported
within 60 minutes had significantly lower KIA mortality

59. Decomposition Results
Percentage of KIA Reduction Attributable to Each Factor
2/3 IS ABOUT
TIME AND
BLOOD!!

60. Time to Death: KIA/DOW
Golden Hour is too late to start DCR…
0
20
40
60
80
100
120
5 minutes
or less
>5
minutes
to 30
minutes
>30
minutes
to 60
minutes
>60
minutes
to 90
minutes
>90
minutes
to 2 hours
>2 hours
to 4 hours
>4 hours
to 6 hours
>6 hours
to 8 hours
>8 hours
to 10
hours
>10 hours
to 12
hours
>12 hours
to 24
hours
>24 hours
to 1 week
>1 week
or more
Number of KIA and DOW Deaths by Time Increment (AFG)
N=457
KIA DOW
JTS 2016.
Must start resuscitation pre-hospital:
Remote DCR (RDCR)!

61. Pre-Hospital Transfusion Saves!
Shackelford,
Del Junco MHSRS 2016.
Transfused on US
MEDEVAC or not
within 30-35 min
of injury

62. IS IT ALL ABOUT SHOCK OR ALL ABOUT
COAGULOPATHY?? OR MAYBE BOTH??
• SHORTER EVAC TIMES = REDUCED SHOCK DOSE
• TRANSFUSE BLOOD: CARRIES OXYGEN = REDUCED SHOCK DOSE
• TIME + BLOOD = IMPROVED SURVIVAL DUE TO REDUCED SHOCK
DOSE
RDCR.org

63. PREHOSPITAL BLOOD FOR HEMOSTATIC
RESUSCITATION
IT`S DOABLE
RDCR.org

64. Norway: Whole Blood from 2013
Whole blood donor program: pre-deployment TTD testing, anti-A/anti-B titers,
universal donor identification.
Transfusion plan: Group A to A, O/low titer to all others.
Frigate has constant store 4 U WB O/low titer stored at 4°C, 14 days (tested,
Gulf of Aden 2013).
Norwegian Navy SOF currently carry GHB with stored WB on each mission.

65. NEW CPG FOR THE NORWEGIAN
ARMED FORCES 01.07.2017
• WHOLE BLOOD GROUP 0 LOW TITER AS THE
PREFERED RESUSCITATION FLUID FOR TRAUMATIC
HEMORRHAGIC SHOCK
• FROM POINT OF INJURY TO ROLE 2
• THE ENTIRE FORCE (NOT SOF ONLY)

66. WHOLE BLOOD TO THEATRE IN GOLDEN
HOUR BOXES

68. FDP
RBC + FDP
WB + FDP
Clear fluids

69. Need Optimal Resuscitative Product
for Trauma-Induced Blood Failure
Mortality is high
Children - higher
Mortality occurs fast
Prehospital deaths occur commonly
High rate of preventable deaths from
hemorrhage

70. Whole Blood
FDA approved
CE Mark
Stored for up to 35 days
2-6 degrees C
450-500 ml per unit
Low titer group O WB
Optimal product for Trauma Induced
Blood Failure

71. Warm vs Cold Whole Blood
• Warm Fresh Whole Blood
– Collected then immediately transfused
– 8 hrs at room temp
• Cold Whole Blood
– Collected
– Tested
– Stored at 4C for up to 35 days
• Preferable 14-21 days
– Low titer group O preferred over ABO specific

72. Perceived Barriers to
Whole Blood
Must be ABO specific
Cannot leukoreduce without losing platelets
Cold platelets are not “functional”

73. Whole Blood Barriers -Disappeared
Low Titer Group O whole blood now standard product
Low titer definition
Range <200-256 for IgM 1
Platelet sparing filters since 2006
Cold platelets have superior hemostatic function
1 Belin TR, et al. J Trauma. 2017

74. Low titer group O whole blood
change in standards
New AABB standards for 2018
5.15 Selection of Compatible Blood and Blood Components
for Transfusion
5.15.1 Recipients shall receive ABO group-compatible Red Blood Cell
components, ABO group-specific Whole Blood, or low titer group O
Whole Blood (for non group O or for recipients whose ABO group is
unknown).
5.27 Urgent Requirement for Blood and Blood Components
5.27.1.1 If low titer group O Whole Blood is used, the BB/TS shall
define low titer group O Whole Blood and shall have policies,
processes and procedures for:
The use of low titer group O Whole Blood.
The maximum volume/units allowed per event.
Patient monitoring for adverse effects.

75. Resuscitation Paradigm
Early
Whole blood to immediately address TIBF
Soon thereafter
Goal Directed Hemostatic Resuscitation
Address global or specific deficits
Whole blood
Components
Antifibrinolytics
Factor concentrates

76. Component Therapy: 680 mL
1U RBC + 1U PLT + 1U FFP + 1 U Cryo
Hct 29%
Plt 80K
65% Coag factors
Whole Blood: 500 mL
Hct: 38-50%
Plt: 150-400K
Coag concentration
100%
Armand & Hess, Transfusion Med. Rev., 2003
Volume and Concentrations Between
Component Therapy vs. Warm Whole Blood

77. Standard Amounts of
Anti-coagulants and Additives in
Reconstituted Whole Blood vs Whole Blood
Component Therapy per Unit:
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
Whole Blood per Unit:
6 x 63ml = 378ml
There is 3 times the volume of anticoagulant and additives
with reconstituted whole blood from components
compared to whole blood
Total= 378ml
Spinella PC, J Trauma. 2009;66:S69-76

78. TO SUM UP – THE WHOLE IS GREATER THAN
THE SUM OF ITS PARTS
Shock and Its Magnitude (oxygen debt) is the main driver of Blood Failure
The Main Thing is to Keep the Main Thing the Main Thing(K.WARD)
• Hb matters in low flow state
• Hb matters for plt adhesion
• Reverse shock as early as possible to reduce shock dose
• Permissive hypotension with syst 80-90 over time might NOT be sufficient as endpoint for shock
reversal.
• Early platelet transfusion to mitigate plt dysfunction/loss/consumption
• Glycocalyx repair with plasma
• Holistic view of shock resuscitation to gain all of the above
RDCR.org
BLOOD FAR FORWARD FOR BLOOD FAILURE USE :WHOLE BLOOD

79. Blood is for bleeding!
Saltwater is for cooking pasta!
Phil Spinella rdcr 2017

80. GCS BELOW 8
ITS TIME FOR CONSIDERATION – NOT INTUBATION

81. “Don’t cling to a mistake just because you spent
a lot of time making it.”

82. DONTDISCONNECTTHEHEARTLUNGMACHINE
PRIORTOSURGERY:KEEPTHEBLEEDINGPATIENTSPONTANEOUSBREATHINGIFPOSSIBLE

83. RCT OR?
• KNOWN PHYSIOLOGY
• EXPERIENCE
• OBSERVATION
• COMMON SENSE
• OR MAYBE BOTH???

84. 88
THOR 2016CDR Geir Strandenes -

85. Prehospital Challenge Outline
Prevention of further oxygen debt accumulation (“sjokkbrems”)
Repayment of oxygen debt
Minimization of the time to oxygen debt resolution
• Permissive hypotension in the presurgical phase – implications
for oxygen debt.
• Strategies to improve oxygen delivery during the prehospital and
early inhospital phase.

87. Acknowledgements
• The Blood Far Forward group
in Bergen :
• Torunn O Apelseth, MD, PhD
• Einar K Kristoffersen, MD, PhD
• Christopher Bjerkvig, MD
• Theodor K Fosse, MD
• Tor Hervig, MD, PhD
• Turid Helen F Lunde, MSc
• Hanne Braathen, BSc
• Joar Sivertsen, BSc
• Håkon Eliassen, Stud Med
Andrew P Cap, MD, PhD, FACP
U.S. Army Institute of Surgical Research, FT
Sam Houston, TX, USA
Kevin R. Ward, MD
Professor Emergency Medicine and Biomedical
Engineering
Executive Director:
Michigan Center for Integrative Research in
Critical Care
Our institutions:
Department of immunology and transfusion medicine, Department of Anaesthesia and Intensive Care,
Section of Cardiothoracic Surgery, Department of Heath Disease, and Laboratory of Clinical
Biochemistry, Haukeland University Hospital, Bergen, Norway
Institute of Clinical Science, School of Medicine and Dentistry, University of Bergen, Norway
Norwegian Naval Special Operations Commando
Norwegian Armed Forces Medical Services
Advisors, debaters and critics in
the THOR Network
Philip C Spinella, MD, FCCM
Division of Critical Care Medicine, Clinical Care
Translational Research Program, Washington
University, St. Louis, US

88. THANK YOU FOR YOUR TIME
RDCR.org

89. IN PRESS