Endpoints of Resuscitation [in Trauma]

AJ Layon, MD, FACPProfessor and Chief

Critical Care Medicine

University of Florida College of Medicine

Gainesville, FL

Basics First

Shock is imbalance of DO2 and VO2

• Resuscitation is complete when...– O2 debt is repaid

– Tissue acidosis is eliminated– Aerobic metabolism restored

Porter JM, Ivatury RR, J Trauma, 1998;44:908.

Severe Under-Resuscitation in Trauma is Shock

• …However we define this and with whatever monitors we use to determine endpoints

• ATLS Manual, 1993– An abnormality of the circulatory system that results in

inadequate organ perfusion and tissue oxygenation…

Lecture goals

• Cellular energetics during "acute illness"

• Systemic organ perfusion monitoring

• Selective organ perfusion monitoring / goals

• Old and new logistics of trauma

Organ Perfusion in Critically Ill Patients

TRAUMA

SIRSMOF

RECOVERYDEATH

O2 DEBT

Realistically, prevention of these is how we earn our salary

From the trauma bay to discharge from the ICU

fatty acids

O2 ATP = ADP+Pi+H+ (energy)

O2

Cellular energetics

Glycolysis (D-glucose to Lactate + 2H+) (energy)

ADP + ADP = ATP + AMP (vasodilatation)

CK reaction (PCr + ADP = H + ATP + Cr)

H+ + HCO3- CO2

free O2 radicals

NADH / NAD

cytosolic redox status

Lactate / pyruvate

1

2

3

4 5

limited to heart, brain, skeletal muscle

xanthine oxidase,

= H2O +

O2

Organ Perfusion in Trauma Patients

cellular parameters

Clinical parameters

Global and regional (organ perfusion) parameters

However…Few words on quality of Resuscitation are Necessary

CrystalloidsBloodFFPPlts

MTP: Class III and beyondEstimated Fluid and Blood Requirements1

(Based on Patient’s Initial Presentation)

Class I Class II Class III Class IV

Blood Loss (ml)Blood Loss (%BV)Pulse RateBlood PressurePulse Pressure (mm Hg)Capillary Refill TestRespiratory RateUrine Output (ml/hr)CNS-Mental Status

Fluid Replacement (3:1 Rule)

Up to 750up to 15%< 100NormalNormal or increasedNormal14 - 2030 or moreSlightly anxious

Crystalloid

750 - 150015 - 30%> 100NormalDecreased

Positive20 - 3020 - 30Mildly anxious

Crystalloid

1500 - 200030 - 40%> 120DecreasedDecreased

Positive30 - 405 - 15Anxious and confusedCrystalloid + blood

2000 or more40% or more140 or higherDecreasedDecreased

Positive> 35NegligibleConfused - lethargicCrystalloid + blood

1For a 70 - kg male

Class IV: 65% ofFactors and 75% Of Plts present

RL vs HTS: HTS wins

Murine hemorrhagic shock versusSham with LR versus Hypertonic SalineResuscitation: PMN activation

Murine hemorrhagic shock versusSham with LR versus Hypertonic SalineResuscitation: PMN activation

Deitch, Shock 2003;19:328Deitch, Shock 2003;19:328

Think TRALI/ARDS /

MOSF / ACS

Hemorrhage and Trauma

• New algorhythm in severe trauma:– Damage control resuscitation strategy– Focused on halting / preventing lethal triad:

• Coagulopathy• Acidosis• Hypothermia

Holcomb JB, et al. Ann Surg. 2008;248: 447 – 458

Old and New Paradigms

Carrico, et al. Transfusion Chapter in Mattox,

Moore and Feliciano

Cosgriff N, et al. Predicting life-threatening coagulopathy in the massively transfused patient:Hypothermia and acidosis revisited. J Trauma. 1997.

Coagulopathy: How Quick ?

• Loss of Coagulation factors– 1 Blood volume (BV) -

35% of factors remain– 2 BVs – 10% - 15%

remain– 3 BVs – 5% remain

• 20% - 30% of activity required for hemostasis

• Factors also consumed with clotting

• 1,088 Pts 1993 – 1998• Arrival to ED from scene ~ 73 min• 24% had coagulopathy (PT > 18, aPTT > 60 sec, TT >

15 sec) • Mortality for those with coagulopathy 46%

vs 11% in those without

Brohi K, et al: J Trauma, 2003;54:1127

Blood & Co: New Trauma Trends

MT = > 10 units PRBC / 24 hrs

Critical Revision of Old Trauma Trends

• Crystalloids are good for you– LR developed for diarrhea

• Fresh whole blood is bad for you• Plasma is a bad resuscitation fluid• Platelets should be given after the “surgical

bleeding” is controlled• Laboratory data are helpful in a rapidly bleeding

patient• RBCs today do not resemble those studied in the 70’s• No data in trauma as whole blood transitioned to

component therapy

ASA Guidelines on FFP Transfusion

• Blood usually coagulates appropriately when:– Coagulation factor concentrations are at least 20% - 30%

of normal – Fibrinogen is > 75 mg / dL

• Clinical coagulopathy from dilution does not occur until:– Replacement exceeds 1 BV or– PT / PTT exceeds 1.5 – 1.8 times control values

• With hypothermia1

– Coagulation enzyme reactions decreased by 10% / °C

1. Armand R, Hess JR: Treating Coagulopathy in Trauma Patients. Trans Med Rev, 2003;17 (3):223 – 231

Hemorrhagic Shock: MTP

• 80% to 85% of combat deaths not preventable– 66% to 80% of 15% to 20% of survivable combat-

related deaths result from hemorrhagic shock

• Recognition / treatment of coagulopathy important– Most Pts requiring MTP die within 6 hrs of admit

• Lethal triad after trauma:– Bleeding, hypothermia, acidosis

Borgman MA, et al. J Trauma. 2007;63:805–813

Hemorrhagic Shock and Resuscitation

Borgman MA, et al. J Trauma.

2007;63:805–813

Mortality by Plasma : RBC Ration = 246 MT’s (2003 – 2005): Military

Borgman MA, et al. J Trauma. 2007;63:805–813

MT: Civilian

Holcomb JB, et al. Ann Surg. 2008;248: 447 – 458

466 / 1574 (29.6%) civilian trauma Pts retrospective analysis of registries

No ISS / AIS differences. Overall survival 59%Range by center: 41% - 74%

FFP:PTL

Holcomb JB, et al. Ann Surg. 2008;248: 447 – 458

Mortality vs mean FFP / RBC ratio byCenter and Variability: Civilian

Holcomb JB, et al. Ann Surg. 2008;248: 447 – 458Massive transfusion practice guidelines should aim for a 1 : 1 : 1 ratio of FFP : Plts : PRBC

RISKS OF FFP and PLATELETS

• Reports of TRALI from the UK haemovigilance program– Suggest risk from FFP ~ 1 in 50,000 to 60,000 units– May now be the commonest cause of death from transfusion– Is the most frequent serious complication of FFP

• In most of the TRALI cases arising from FFP– Female donors identified as the source of the antibodies– ARC recently limited female donors

• Further lowering risk of a rare complication

Eder AF, et al. Transfusion, 2010;50:1732-1742Wiersum – Osselton JC, et al. Transfusion, doi: 10.1111/j 1537-2995.2010.02969.x [4 April, 2011]Rios JA, et al. Transfusion, doi: 10.1111/j.1537-2995.2010.02991.x [11 April, 2011]

RISKS OF FFP and PLATELETS

Eder AF, et al. Transfusion, 2010;50:1732-1742

Resuscitation Endpoints

• Historical– BP, HR, UOP– However...

• 80% - 85% under-resuscitated when values normalized– Elevated lactate– Decreased SVO2

Scalea et al, CCM, 1994;22:1610.Abou-Khalil et al, CCM, 1994;22:633.

65

BP and Coronary Autoregulation

Bellomo et al. Critical Care 2001;5:294

10 30 50 70 90 110 1300

20

40

60

80

100

120

Flo

w (

% o

f n

orm

al)

Perfusion pressure (mm Hg)

Heart Hypertrophicheart

0 25 50 75 100 125 1500

25

50

75

100

Mean Arterial Blood Pressure (mm Hg)

Cer

ebra

l Blo

od F

low

(c

c/10

g/m

in)

50 mm Hg 80 mm Hg

Normal autoregulation

Disrupted autoregulationAB

Zone of NormalAutoregulation

Blood Pressure (MAP) is Brain Flow

65

Range of Hyperfusion

Additional Endpoints of Resuscitation

• Oxygen delivery• SvO2 and ScvO2

• Arterial base deficit• Arterial lactate• Gastric tonometry……….• Near Infrared Spectroscopy (NIRS)• Physical examination

• DO2 = Q X CaO2 = Q X [(Hb x 1.39 x SaO2) + 0.003 x PaO2)]

For a CO = 5 and Hb = 15: • DO2 = 1000 mL / min or 620 mL / min / m2

• VO2 = Q X (CaO2 - CvO2) = 240 mL / min or 170 mL / min / m2

• O2ER = (CaO2 - CvO2) / CaO2 = 0.27%............or

(SaO2 - SvO2) / SaO2

Back to basicsOrgan Perfusion in Critically Ill Patients

(Valid for Everyone)

Cytopathic Tissue Hypoxia in Critical Illness is Proportional to SVO2 (& CI)

Mixed venous oxygen saturation (SvO2 ) and mitochondrial respiration measured as mitochondrial-dependent reduction of WST-1 (abs, absorbance) for 15 patients with septic shock

Rs = .61

P < 0.05

Roulos M. Crit Care Med. 2003 Feb;31:353 – 8

Shoemaker WC, et al. Chest. 1992;102:208 – 215

And in fact Net Cumulative VO2 Deficit is much more for Non Survivors.

“Optimization” of DO2 by Optimizing SVO2 ?

Gattinoni L, et al. N Engl J Med. 1995;333:1025 – 1032

Gattinoni L, et al. N Engl J Med. 1995;333:1025 – 1032

“Optimization” of DO2 by Optimizing SVO2 ?

Then a number of ER guys showed some magic

49.2%

33.3%

0

10

20

30

40

50

60

Standard Therapy N = 133

EGDTN = 130

P = 0.01 *

Rivers E, et al. N Engl J Med. 2001;345:1368 – 1377

Rivers Protocol: EARLY GOAL (SsvcO2 > 70%)

Preload End Point ?

Cardiac Filling Pressures: Not Appropriate to Predict Response to Volume Challenge

Osman D,et al. Crit Care Med. 2007;35:64 – 68

Interpretation of an Elevated PAOP (20)

A. High extracardiac pressure with normal preload

B. Normal extracardiac pressure and increased preload in a normally compliant ventricle

C. Normal / decreased preload of a poorly compliant ventricle

Scattergram of cardiac index (Cl) vs pulmonary artery wedge pressure (PAWP) with first-order regression line of best fit (Cl = 3.103 + 0.098 x PAWP) (n = 131,

r = .418, P < .001)

Scattergram of cardiac index (Cl) vs right ventricular end-diastolic volume index (RVEDVI) with first-order regression line of best fit (Cl = 1.094 + 0.028 x RVEDVI) (n =

131, r = .613, P < .001)

Baseline ΔPP Predicts Volume Responsiveness in Hypotensive Critically

Ill Patients

Michard F, et al. Am J Resp Crit Care Med. 2000;162:134 – 138

50

40

30

20

10

0

y = 1.01x – 1.46r2 = 0.85

0 10 20 30 40 50

Ch

ange

s in

car

diac

inde

x (%

)

Baseline ΔPP (%)

Baseline ΔPP Predicts Volume Responsiveness in Hypotensive Critically Ill Patients

Michard F, et al. Am J Resp Crit Care Med.2000;162:134 – 138

LactateBase Deficit

Vincent Acta Anaesthesiol Scand 1995;39(suppl 107): 261-6

Lactate and DO2

LA

DO2

Bakker Chest 1991;99:956-62Ngyen Crit Care Med 2004;32:1637-42

Persistent Lactic Acidosis = Decreased Survival

DO2 VO2 Lactic Acid

*

Mortality

Number of Pts

500

400

300

200

100

00 -5 -10 -15 -20 -25 -30 -35 -40 -45

0

20

40

60

80

100

BASE DEFICIT (mmol/L)

PATIENTS

%

MORTALITY

Rutherford et al, J Trauma, 1992;33:417.Rutherford et al, J Trauma, 1992;33:417.

Increased BD = Decreased Survival

BE vs MOSF Post Trauma

0

5

10

15

20

25

30

35

40

BE<=4

BE > 4

% MOSF

Kincaid, J Am Coll Surg, 1998;187:384 – 392

*

* p < 0.001

Organ Perfusion in Critically Ill Patients

Persistent Base Deficit = Decreased Survival

0 1 2 3 4 5

-13

-12

-11

-10

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

1

2

3

4

Days after admission

Sta

nd

ard

bas

e ex

cess

(m

Eq

/L)

Survivors

Non survivors

#

#

* #

Park M, et al. Evolutive standard base excess and serum lactate level in severe sepsis and septic shock patients resuscitated with early goal directed therapy: Still outcome markers ? Clinics. 2006;61:47 – 52

CO2 freely diffuses in tissuesPCO2 in the balloon is in equilibrium with mucosal PCO2

Arterial HCO3- = mucosal HCO3

-

pHi = 6.1 + (log [HCO3-] / mucosal PCO2)

pHi - pHa gap PtCO2 - PaCO2 gap

Gastric Tonometry

Organ Perfusion in Critically Ill Patients

2COCO2

2COCO22COCO2

2COCO22COCO22COCO2

Gastric tonometry is based on the principle that tissue production of CO2 rises sharply with tissue dysoxia.

Weil CCM 1999 Vol 27 (7): 1225-29

Organ Perfusion in Critically Ill PatientsSublingual Capnometer

1) accessible2) high PC stores

Sublingual PCO2 (PSLCO2)

Marik PE. Chest 2001;120:923-927

Povoas H, et al. Chest 2000;118:1127-1132

†Weil MH, et al. Crit Care Med. 1999; 27:1225-1229

30

mmHg

15070

Orthogonal Polarization Spectral Imaging: Sublingual Circulation

- Normal

De Backer Daniel, et al. Am J Resp Crit Care Med. 2002;166:98 – 104

- Sepsis - Hypoperfusion

Orthogonal Polarization Spectral Imaging: Sublingual Circulation

De Backer Daniel, et al. Am J Resp Crit Care Med. 2002;166:98 – 104

OPS Imaging: Sublingual Circulation

Creteur J, et al. Intensive Care Med. 2006;32:51–523

• 18 consecutive MV Pts in early phase (within 24 h) of septic shock, defined as:• Hypotension (MAP < 65 mmHg) requiring a pressor agent

• Dopamine > 5 μg/kg/min or NE• In the presence of an infection

• Pts treated with midazolam, morphine, H2 receptor blocker

Near-Infrared Spectroscopy(NIRS)

• Continuous, noninvasive tissue oxygen monitor

Lima AP. Int Care Med. 2005;31:1316 – 1326

Cuff released

Baseline

Co

nce

ntr

atio

n c

han

ges

(m

M)

Arterial oclusion

NIR-lightDetection

ProbeNIR-lightEmission Probe

Near-Infrared Spectroscopy: NIRS

• Uses light transmission and absorption to measure concentration of Hb, StO2 and cyt-aa3 in tissue

• Global assessment of oxygenation in arterial, venous and capillary compartments– Limitation

• Affected by edema– Application

• Brain• Skeletal muscle and visceral ischemia

Regional Perfusion Markers

• McKinley et. al., 2000• Severely injured trauma

patients

Found the measurementof tissue oxygenationcorrelated well withoxygen delivery, basedeficit and lactate levels.

StO2 (20 mm; skeletal muscle)

StO2 (6 mm; subcutaneous)

DO2I

1009080

70

60504030

2010

0

800

1000

600

400

200

0

StO

2 (

%)

PgCO2

PgCO2 – PaCO2gap

80

70

60

50

40

30

20

200

Pg

CO

2, g

ap (

mm

Hg

)

SvO2

BD

lactate

01020

30

4050

6070

80

90S

vO2 (

%)

0 4 8 12 16 20 24 28 32 36-2

0

2

4

6

8

BD

(m

Eq

/L),

la

cta

te (

mM

)

TIME (hr)endresuscitation

start

End Point of Resuscitation in Trauma: Conclusions

• This was a Troglodytic field– Now better– No ABC, no fast surgeon, no mission accomplished

• Non-crystalloids resuscitation is the new buzz – PRBC / FFP / Plts / Cryoprecitate

• BP / Pulse / UOP / MS practical but not accurate• At some point DO2 / VO2 relationship needs to be evaluated

and corrected if feasible• Biomarkers are very reasonable endpoints, as long as

sampled frequently • Fancy toys coming………..stay tuned