hypothermia for hemorrhagic shock: it’s cool to be cool!!
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Hypothermia for Hemorrhagic
Shock:It’s Cool to be
Cool!!
Samuel A. Tisherman, MDSamuel A. Tisherman, MDAssociate ProfessorAssociate ProfessorSurgery and Critical Care MedicineSurgery and Critical Care MedicineSafar Center for Resuscitation ResearchSafar Center for Resuscitation ResearchUniversity of PittsburghUniversity of Pittsburgh
Mechanisms of Benefit
Energy failureEnergy failure Oxidant injuryOxidant injury Delayed neuronal Delayed neuronal
deathdeath ExcitotoxicityExcitotoxicity ICPICP Edema formationEdema formation
Cytoskeletal Cytoskeletal protein protein degradationdegradation
BBB permeabilityBBB permeability IL-1IL-1 production production Neutrophil Neutrophil
accumulationaccumulation
Who cares?
Predisposition in Trauma Patients
Exposure (field and trauma bay)Exposure (field and trauma bay)– Opening of body cavitiesOpening of body cavities
Blood lossBlood loss Infusion of cold fluidsInfusion of cold fluids Limited heat productionLimited heat production
– ShockShock– Sedation, anesthesia, EtOH and drugsSedation, anesthesia, EtOH and drugs
Hypothermia
Therapeutic/controlled
Exposure/uncontrolled
Temperature Levels
MildMild 32-3632-36ooCC ModerateModerate 28-3228-32ooCC DeepDeep 10-2010-20ooCC ProfoundProfound 5-105-10ooCC UltraprofoundUltraprofound <5<5ooCC
Dying Patterns from Hemorrhage
UncontrolledHS
Limited FRHypothermia
Pharmacologic hibernation
Maintain pulseTransport
Delayed ResuscitationResuscitative Surgery
ExsanguinatingHemorrhage
HypothermicPharmacologic
Preservation“Suspended Animation”
Allow circulatoryarrest
Lose pulse
Moderate hypothermia and HS
Meyer and Horton, Curr Surg, 1988.
Time (min)0 50 100 200150 250 300
% s
urv
ivin
g
0
20
40
60
80
100
HthGroup 2
O2-HthGroup 4
O2Group 3
ControlGroup 1
Kim, et al. J Trauma, 1998.
0
2
4
6
8
10
0 24 h 48 h 72 h
Num
ber
of r
ats
aliv
e
Time
Prolonged Hypothermia Group 3
Brief Hypothermia Group 2
Normothermia Group 1
(9/10)
(7/10)
(3/10)p = 0.02 vs. Group 3; p = 0.18 vs. Group 2
Survival from Pressure-controlled HS
Prueckner, J Trauma, 2001.
Hemorrhagic shock Resuscitation to 4 h
MAP
Temp. (rectal)
40 mmHg to30% uptake
G. I: 37.5 °C to 12 h
G. II: 34 °C to 12 h
35 °C
Observation to 72 h
G. I
II 2
h 3
4 C
Rewarming vs. Continued Hypothermia after HS
SCRR. 2001Wu, et al. 2002
Temp.under
controlfor
12 h
0 25 50 750
2
4
6
8
Resuscitation Time (h)
Rewarmed
Hypo-12 h
Hypo-2 h
SCRR. 2001
Rewarming vs. Continued Hypothermia after HSS
urv
ivor
s
Hemorrhagic shock Resuscitation to 4 h
MAP
Temperature (rectal)
40 mmHg
Group I: 37.5 °C to 12 h
Group II: 34 °C to 12 h35 °C
Observation to 72 h
50% uptake of
shed blood
3ml/100g over 15 m
in
SCRR. 2002
Rewarming vs. Continued Hypothermia after HS
0 10 20 30 40 500
2
4
6
8
Sur
vivo
rs
Resuscitation Time (h)
Cooling Group
Rewarming Group
P = 0.0029
Temp Controlled
Rewarming vs. Continued Hypothermia after HS
Very Prolonged HS (6 h)Hypothermia
0 RT 0 RT 24 h RT 48 h RT 72 h0
2
6
12
14
# S
urvi
vors Hypo-10 min (p=0.005 vs normothermia, Log Rank [Peto])
Hypo-1 h (p=0.01 vs normothermia, Log Rank [Peto])
Normothermia
HS Temp.Controlled Observation
10
8
4
HS: Hemorrhagic shock; RT: Resuscitation time (hours)
Hypothermia isa double-edgedsword.
Hypothermia and Trauma High ISSHigh ISS
– HypothermiaHypothermia– Decreased shivering, Decreased shivering,
thermoregulation, heat productionthermoregulation, heat production Coagulopathy and acidosisCoagulopathy and acidosis
– "Damage control laparotomy""Damage control laparotomy"
Hypothermia - complications
CoagulopathyCoagulopathy– Platelets -Platelets - number and function, number and function,
TxB2TxB2– Elevated PT and PTTElevated PT and PTT– ?Increased fibrinolysis?Increased fibrinolysis
Dysrhythmias and hypotensionDysrhythmias and hypotension Metabolic acidosisMetabolic acidosis InfectionsInfections
Preclinical Pig Study
Pressure-controlled HSPressure-controlled HS HemodilutionHemodilution Normothermia vs hypothermia (34Normothermia vs hypothermia (34ooC)C) LaparotomyLaparotomy
– Excise edge of liverExcise edge of liver– Measure blood lossMeasure blood loss
Coags, platelets, TEG, ACTCoags, platelets, TEG, ACT
Wu, in preparation.
0
200
400
600
800
1000
1200
1400
1600
1800
2000
0 50 100 150 200 250 300 350
Hypothermia
Normothermia
Heparin 200 u/kg
Resuscitation time (min)
Cum
ula
tive
blo
od lo
ss (
ml)
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HYPOTHERMIA AND HEMORRHAGIC SHOCK IN PIGSBLEEDING FROM THE INJURED LIVER
Wu, et al. SCCM 2002
PRECLINICAL STUDY OF HYPOTHERMIADURING HS-PIGS
Wu, et al. SCCM 2002
Coagulation Tests in Pigs at 3 h after HS and Liver Injury
Thromboelastograph (TEG)PT (sec) PTT (sec) Platelets (/l)
R (min) K (min) MA (mm) Alpha ()
Normothermia 11.2 22.9 280 3.5 62.4 69Hypothermia 12.1 19.6 236 10.2 3.7 53.361
ACT (sec)
127.721.1
140.0
Hypothermia and Trauma Luna, et al (U of Washington)Luna, et al (U of Washington)
– T>36T>36ooC (n=32): ISS 28, survival 78%C (n=32): ISS 28, survival 78%– T=34-36T=34-36ooC (n=41): ISS 29, survival 59%C (n=41): ISS 29, survival 59%– T<34T<34ooC (n=21): ISS 36, survival 41%C (n=21): ISS 36, survival 41%
Jurkovich, et al (U of South Alabama)Jurkovich, et al (U of South Alabama)– ISS 25-29ISS 25-29
>33>33ooC: survival 97%C: survival 97% <33<33ooC: survival 50%C: survival 50%
J Trauma, 1987.
Hypothermia and TRISS UCSDUCSD 173 with ISS >9 and known core 173 with ISS >9 and known core
temptemp Hypothermic pt: n=37Hypothermic pt: n=37
– More hypotensiveMore hypotensive– Survival as predicted by TRISSSurvival as predicted by TRISS– No difference in ICU days for No difference in ICU days for
survivorssurvivors
Steinemann, J Trauma, 1990.
Prospective Hypothermia Study
Harborview Medical Center, SeattleHarborview Medical Center, Seattle Core temp Core temp <<34.534.5ooC and PAC neededC and PAC needed Standard TxStandard Tx
– Warm fluids, gases, air blanket, hatWarm fluids, gases, air blanket, hat TreatmentTreatment
– Continuous arteriovenous rewarmingContinuous arteriovenous rewarming
Gentilello, et al. Ann Surg, 1997.
Continuous arteriovenousrewarming technique.
Gentilello, et alAnn Surg, 1997.
Prospective Hypothermia Study
Survival to dischargeSurvival to discharge– SR = 14 (50%)SR = 14 (50%)– CAVR = 19 (66%)CAVR = 19 (66%)
CAVRCAVR– More late deaths - ?SR weeded out More late deaths - ?SR weeded out
sicksick No significant difference in coagsNo significant difference in coags
Gentilello, et al. Ann Surg, 1997.
Clinical Trials
1. Mild hypothermia for HS
2. Suspended animation for exsanguination arrest
Financial: Funding
Ethical: Consent
Medical: Protocols
Political: Centers
Snowbird, Utah, SHOCK Society annual meeting, June, 2000
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