Samuel Tisherman at The Big Sick 2018 in Zermatt. This is the story of deep hypothermia as a means of buying time to surgically save the lives of otherwise unsalveagable trauma patients. This is essentially suspended animation. Hear how this technique has evolved from one of the pioneers and learn about the ongoing efforts to establish its potential benefits in humans through the EPR-CAT study.

1. Exsanguinating trauma:
From CPR to EPR
Samuel A. Tisherman, MD
Professor
Department of Surgery, Program in Trauma
University of Maryland School of Medicine

2. Disclosures
• Co-author of patent
– “Emergency Preservation and Resuscitation Method”
• Grant support
– US Department of Defense
• Off label use
– Saline
– Cardiopulmonary bypass pumps and cannulas

3. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

4. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

5. Peter Safar ABCs of CPR
Hypothermia: Start within 30 minutes if no sign of CNS recovery

6. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

7. Hypothermia after cardiac arrest

8. Enthusiasm

9. HACA Temperatures

10. Targeted Temperature Management: 33 vs 36oC
Nielsen N et al. N Engl J Med, 2013.

11. Nielsen N et al. N Engl J Med, 2013.
Targeted Temperature Management: 33 vs 36oC

12. 2015 ERC/AHA Guidelines: Post-cardiac Arrest Care
• Comatose (ie, lack of meaningful
response to verbal commands) adults
• Targeted temperature management
–32°C to 36°C
–At least 24 hours after achieving goal
• Prevent fever for >72 hrs

13. Traumatic Cardiac Arrest and TTM
• Shock Trauma Center
• 2008-2010
• 6 pt with coma after arrest during initial assessment
• 32-34oC for 24 h
• Median ISS 27, median arrest duration 8 min
• No complications of hypothermia
• Outcome
– 1 died (had prehospital arrest)
– 2 D/C’d to chronic care, GCS 11-Trached
– 3 D/C’d to active rehab
Tuma, et al. J Trauma, 2011.

14. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

15. Trauma case at Shock Trauma
• 23 yo male
• Stab wound to the heart
• Arrest in Trauma Resuscitation Unit

16. CPR doesn’t work in trauma

17. Cardiac arrest from trauma
0 20 40 60 80 100
Overall
Penetrating
Blunt
Chest
Abdomen
Survival (%)
Rhee, JACS, 2000

18. Dr. Peter
Safar
Col. Ron
Bellamy
Time to Death in Combat Casualties

19. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

20. Influences
Hth after
CA
Drowning
Circ
arrest

21. Emergency Preservation and Resuscitation
• “Protection and preservation of the organism during
circulatory arrest of 2 h or longer for transportation and
control of bleeding during pulselessness followed by delayed
resuscitation.”
• Could allow survival from otherwise lethal insults

22. Decrease:
O2 consumption
Free radicals
Inflammation
Excitatory neurotransmitters
Coagulopathy
Stress
Shivering
Hypothermia and Trauma

23. Predisposition in Trauma Patients
• Exposure (field and trauma bay)
– Opening of body cavities
• Blood loss
• Infusion of cold fluids
• Limited heat production
– Shock
– Sedation, anesthesia, EtOH, drugs

24. Triad of Death

25. Retrospective studies
Increased injury severity
Decreased temperature
Increased mortality

26. PA Trauma Outcome Study
• Statewide trauma registry
• 38,520 trauma patients (2000-2002)
– 1,921 (5%) hypothermic on admission (<35oC)
• Adjusted for everything possible
– Age
– Injury severity
– Mechanism of injury
– Route of temp measurement
• Odds ratio for death 3.03 (2.62-3.5)
Crit Care Med, 2005.

27. Hypothermia will add
10 years to your life

29. Safar Center for Resuscitation Research

30. Time (h)
0 4 8 12 16 20 24
0
8
#Survivors
HS
3 h
7
6
5
4
3
2
1
Norm, n=8
Hypo-Ice, n=8
*
Hypo-Rm, n=8
p<0.05 (Hypo-Rm vs Norm)
Wu, et al. J Trauma, 2005.
Pig Survival

31. Why the dichotomy?

32. Outline
CPR
Post-arrest
hypothermia
Cardiac
arrest and
trauma
Hypothermia
and trauma
EPR

34. 0
20
40
60
80
100
120
Time
MAP(mmHg)
28
29
30
31
32
33
34
35
36
37
38
Temperature(o
C)
Exsanguination Cardiac Arrest Model
Exsanguination
Cardiac Arrest
15-180 min
Bleed Flush CPB
Tty
MAP
VF

35. Hypothermia Dose Response
15-20 min
• 34oC
30 min
• 28oC
60 min
• 15oC
90 min
• 10oC

36. 5 Brain Death
4 Coma
3 Severe Disability
2 Moderate Disability
1 Normal
90 min 120 minFinal OPC
Behringer, CCM, 2003.
Volume
>500 ml/kg
Whole body
Exsanguination Cardiac Arrest (Tty 10oC)

37. Mechanisms

38. Drug list
 Adenosine
 Thiopental
 Thio/Phenytoin
 MK801
 YM872
 Nimodipine
 Diltiazem
 Lidocaine
 Insulin/glucose
 W7
 Cyclohexamide
 Tempol
 Cyclosporine A

39. Drug list
 Adenosine
 Thiopental
 Thio/Phenytoin
 MK801
 YM872
 Nimodipine
 Diltiazem
 Lidocaine
 Insulin/glucose
 W7
 Cyclohexamide
 Tempol
 Cyclosporine A

41. Prolonged HS->arrest, EPR
CPR group
EPR group
MAP
Continuous bleeding Cardiac arrest CPB
Spleen transection
HS time
CPR:124±11 min
SA: 128±17 min
Splenectomy
Wu et al. Circulation, 2006.

42. Prolonged HS->arrest, EPR
Overall Performance
Category CPR
EPR-I
(hypo-12h)
EPR-II
(hypo-36)
5 Dead

  
4 Coma  
3 Severe disability 
2 Moderate disability 
1 Normal  
Wu et al. Circulation, 2006.
*
*Seizures

43. We’re not the only ones

44. USUHS Model
HypoThermosol®

45. Rhee and Alam
Cooling
Rewarming

46. 0
20
40
60
80
100
Time
0
5
10
15
20
25
30
35
40
Temp(ºC)
5min
exsanguination
20minEPR
(including
aorticflush)
1minCA
60min
CPB
(Temp N-EPR)
(Temp H-EPR)
MAP(mmHg)

47. Shock Trauma Center
University of Maryland Medical Center
Emergency Preservation and Resuscitation
for Cardiac Arrest from Trauma

48. Baltimore

49. Specific aims
• Rapidly identify potential candidates for EPR within 5 min of
pulselessness.
• Rapidly induce EPR by infusing ice-cold saline to attain a
tympanic membrane temperature (Tty) of 10oC.
• Following hemostasis, delayed resuscitation will be via
cardiopulmonary bypass (CPB).
• Survival without significant neurologic deficits.

50. Subject Inclusion Criteria
• 18 - 65 yo
• Signs of life (pulse, respirations,
reactive pupils, or spontaneous
movement) present within 5 min of
ED/TRU arrival or in the ED/TRU or OR
• Remains pulseless after OCCPR and no
response to clamping aorta

51. Subject Exclusion Criteria
• No signs of life for > 5 min
• Traumatic brain injury
• Electrical asystole
• Obvious non-survivable injury
• Massive tissue trauma involving multiple sites
• Pregnancy
• Prisoner

52. 0
10
20
30
40
50
60
70
80
90
100
0
5
10
15
20
25
30
35
40
Emergency
Preservation
Time
MeanArterialPressure(MAP,mmHg)
TympanicTemperature(Tty,oC)
Trauma
Final gasp
Lose pulse
Open chest Transport to OR
Hemostasis
<60 min
Delayed
resuscitation
Aortic
flush
Tty
MAP

53. Aortic
cannula
Drain blood via
right atrial
appendage

54. Outcome
• Survival to D/C without major neuro sequelae
• Direct complications of the technique
• Coagulopathy
• Organ system failures
• Survival (28 d)
• Neurologic function (12 months)

55. Trauma
surgeons
Trauma
Resusc Unit
Trauma
anesthesiologists
Perfusionists
Cardiac
surgeons
OR staff
Cardiac
anesthesiologists
Blood bank
Team

56. Training

57. Simulation Training

58. Control groups
• Concurrent patients
– Meet criteria, but team not
available
• Historical controls

59. Regulatory hoops
FDA
DSMB
IRB
CC/PD

60. Community consultation/Public disclosure
http:/ / nyti.ms/ 1pX2UEl
HEALTH | NYT NOW
Killinga Patient toSave HisLife
By KATE MURPHY JUNE 9, 2014
PITTSBURGH — Trauma patients arriving at an emergency room here after
sustaining a gunshot or knife wound may find themselves enrolled in a startling
medical experiment.
Surgeons will drain their blood and replace it with freezing saltwater.
Without heartbeat and brain activity, the patients will be clinically dead.
And then the surgeons will try to save their lives.
Researchers at the University of Pittsburgh Medical Center have begun a

61. Code Black

62. New Technology

63. Summary
• Non-traumatic cardiac arrest
– Targeted temperature management
• Profound hemorrhagic shock
– Spontaneous mild hypothermia bad
– Therapeutic mild hypothermia good (maybe)
• Exsanguination cardiac arrest
– Emergency Preservation and Resuscitation

64. Trauma in 2412

65. Thanks