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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†

†

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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