Optimal animal model for prehospital hemorrhagic shock with panel

Optimal animal model for prehospital hemorrhagic shock with panel

WorseAnimalShockModelintheWorld:
ExceptforAllOthers
TimeforPhysiologicPhenotyping
KevinWard,MD
MichiganCenterforIntegraDveResearchinCriDcalCare
UniversityofMichigan
BiphasicOxygenDelivery/ConsumpDonRelaDonship
IdealTargets:FirsttoChange….LasttoNormalize?
WhereisthePaDentonthisCurve????
OxygenDebt
TheMagnitude(DegreeandTime)
thatVO2isBelowCriDcalDO2
MagnitudeofTotalBodyIschemia?
IndirectCalorimetry
VO2 pattern after 4 minutes of Exercise
RepayingtheDebt
•  NotenoughjusttoResolveDeliveryDependentVO2
•  LessonsLearnedFromExercise
–  OxygenAlreadyStored
•  0.3litersstoredinmuscle
•  1literstoredinhemoglobin:0.25litersinother
fluids
•  0.5litersstoredinlung
–  ReplenishEnergy
•  2literstoreplenishphosphagensystem
•  8literstoreplenishglycogen-lacDcacidsystem
MakesMeNervousAboutHypotensiveResuscitaDon(Prolonged)
Level of Oxygen Debt Directly Linked
To Inflammatory Response and Immune
Dysfunction
O2Debtvs.HemorrhageVolume
O2 Debt vs. Hemor Amount (mL)
1600.0
Hemor Amount (mL)
1400.0
1200.0
1000.0
800.0
600.0
r = 0.73
400.0
200.0
0.0
0.0
20.0
40.0
60.0
O2 Debt
80.0
100.0
O2Debtvs.HemoglobinLevels
O2 Debt vs. Hemoglobin
12
Hemoglobin
10
8
6
4
2
0
0.0
50.0
100.0
O2 Debt
150.0
200.0
O2Debtvs.Lactate
Lac vs. O2 debt (Hemorrhage)
10
Lactate
8
6
4
2
r = 0.84
0
0.0
20.0
40.0
60.0
O2 Debt
80.0
100.0
O2Debtvs.Lacate:Post-ResuscitaDon
DangerofUsingLacate
Lac vs. O2 debt (Post-Resuscitation)
10
Lactate
8
6
4
r = 0.27
2
0
0.0
50.0
100.0
O2 Debt
150.0
200.0
Animalpayingbackdebtandlactatenormalizing
100.0
12
10
80.0
6
40.0
4
20.0
2
30
m
in
60
m
in
90
m
12 in
0m
15 in
0m
18 in
0m
in
PR
10
0%
%
75
%
50
25
%
0
0%
0.0
Time points
O2 debt
Lactate
Lactate
60.0
BL
O2 Debt
8
20.0
2
0.0
0
Time points
O2 debt
Lactate
75
50
25
Lactate
4
30
m
in
60
m
in
90
m
in
12
0m
in
15
0m
in
18
0m
in
40.0
PR
6
10
0%
60.0
%
8
%
80.0
%
10
0%
100.0
BL
O2 Debt
AnimalreaccumulaDngdebtwithlactategoingup
AnimalparDallypayingbackdebtandlactatenormalizing
0.0
0
75
50
25
30
m
in
60
m
in
90
m
in
12
0m
in
15
0m
in
18
0m
in
2
PR
20.0
10
0%
4
%
40.0
%
6
%
60.0
0%
8
Time points
O2 debt
Lactate
Lactate
10
80.0
BL
O2 Debt
100.0
Baseline
O2Debt80cc/kg:50%BloodLoss
O2Debt80cc/kg:30%Bloodloss
O2Debt40cc/kg:50%BloodLoss
SubjectsFallOutPresyncopeatManyDifferentLevels
ReflecDngPhysiologicReserve
HumanLBNP
FCD
FCD (mm-1)
0.015
*
0.013
0.011
0.009
0
20
40
60
80
MAP
MAP (mmHg)
105
100
*
95
85
75
0
20
40
60
LBNP Level (%)
80
100
Baboon Comparisons
N = 14
Hemorrhage Procedure
LBNP Procedure
Hemorrhage (50 ml/min/kg)
Four weeks after Hemorrhage study
Baseline: 10 min
Baseline: 10 min
Total 25% Hemorrhage
4 steps (7 min/step)
Set LBNP to match CVP and/or PP
4 previous hemorrhage steps (7 min/step)
Hinojosa-Laborde et al, J Appl Physiol 116:406-415, 2014
% Change Stroke Volume
Baboon Hemorrhage/LBNP
vs. Human LBNP
0
-20
-40
Baboon Hemorrhage
Baboon LBNP
-60
Human LBNP
-80
0
12.5% 18.75%
6.25%
0%
-10
-20
-30
-40
-50
Hinojosa-Laborde et al, J Appl Physiol 116:406-415, 2014
-60
25%
-70
Hemorrhage
-80 LBNP, mmHg
Baboon Hemorrhage vs. LBNP
Specificity
Low Tolerance (N = 5)
High Tolerance (N = 9)
Compensatory
Reserve
1.0
0.8
0.6
0.4
0.2
0.0
0
6.25 12.5 18.75 25
% Hemorrhage
Hinojosa-Laborde et al, Am J Physiol 2016 (in press)