11

Hyperoxygenation During Hyperoxygenation During CPB:CPB:

When Should We Use It? When Should We Use It?Gary Grist RN CCP, Chief PerfusionistGary Grist RN CCP, Chief Perfusionist

The Children’s Mercy Hospitals and ClinicsThe Children’s Mercy Hospitals and ClinicsKansas City, MissouriKansas City, Missouri

ggrist@cmh.eduggrist@cmh.eduNo DisclosuresNo Disclosures

22

Some consider it a fact that use of hyperoxia on cardiopulmonary bypass (CPB) has negative effects on patient outcome by increasing the danger of oxygen toxicity or reperfusion injury. This belief has become a 'sacred cow' among many perfusionists. However, the manipulation of oxygen on CPB can be used to the patient's benefit. It is incumbent upon the perfusionist to understand the need for the manipulation of oxygen concentration and master the techniques needed to provide the patient with the greatest benefit. A 'one size fits all' approach to oxygenation strategy, be it normoxia, hyperoxia, or something in between can rob the patient of the benefits that the free range of oxygen manipulation, from high to low, can provide. Oxygen Pressure Field Theory conceptualizes the manipulation of oxygen concentration such that the perfusionist can understand the mechanics of microvascular gas exchange.

Hyperoxia can be beneficial in one situation and detrimental in another as can normoxia. This presentation discusses oxygen manipulation in six clinical situations.

1. Nitrogen entrainment: Special equipment has shown that gaseous microemboli (GME) may occur in the cerebral circulation of any patient on CPB. The GME are most numerous during interventions by perfusionists and were associated with the worst neuropsychological outcomes. Most bubbles that enter the CPB circuit are initially composed of room air; approximately 70% nitrogen, 19% oxygen, 5% carbon dioxide and 6% water vapor. GMEs of this composition are likely to occlude small arteries and capillaries and cause tissue ischemia. During the periods of high risk for GME generation and by using Boyles Law, the perfusionist can change these bubbles to approximately 0% nitrogen, 89% oxygen, 5% carbon dioxide and 6% water vapor. This GME composition is much less likely to result in capillary occlusion.

2. Hemodilution: The reduced oxygen delivery common during CPB as a result of hemodilution can be counter-acted to a limited degree by the use of hyperoxia. Hyperoxia is commonly used for humans in major, non-cardiac surgery and has shown to 1) be safe during anesthesia with no adverse side effects, 2) reduce the need for blood transfusion, 3) preserve myocardial oxygenation during low hematocrit, 4) reverse anemic hypoxic ECG changes, 5) increase sub-endocardial oxygen delivery, 6) reverse non-cardiac tissue hypoxia caused by anemia and 7) reduce the risk of wound infection.

3. Metabolic acidosis: Increases in base deficient caused by suboptimal perfusion (shock) can be significantly reduced using various degrees of hyperoxia.

4. Deep hypothermic circulatory arrest (DHCA): Hyperoxia can be used prior to DHCA to 'oxygen load' tissues. This can extend the period of safe circulatory arrest before anaerobic metabolism begins by approximately 20 minutes.

5. Oxygen toxicity: Oxygen toxicity is frequently confused with reperfusion injury, but it occurs when circulation is good, there is no acidosis, and the antioxidants are functioning properly. However, the amount of oxygen present in the tissues overwhelms the antioxidants' ability to neutralize reactive oxygen species. The perfusionist who is aware of the circumstances during which oxygen toxicity occurs can take the proper precautions with oxygen manipulation to prevent tissue damage.

6. Reperfusion injury: Reperfusion injury is frequently confused with oxygen toxicity, but it occurs when circulation is poor and acidosis is present which deactivates the antioxidants. Reperfusion injury can occur even during low oxygen concentration and can be caused iatrogenically by the perfusionist. The perfusionist can prevent tissue damage when there is reperfusion injury potential (RIP) and he/she can prevent damage by not allowing RIP to develop; in both instances using oxygen manipulation.

33

OBJECTIVESOBJECTIVES

To briefly describe the oxygen pressure field theory and To briefly describe the oxygen pressure field theory and discuss scenarios where oxygen manipulation on discuss scenarios where oxygen manipulation on cardiopulmonary bypass may be helpful to improve cardiopulmonary bypass may be helpful to improve patient outcomes.patient outcomes.

Six situations for oxygen manipulation:Six situations for oxygen manipulation:1.1. Nitrogen entrainmentNitrogen entrainment2.2. HemodilutionHemodilution3.3. Metabolic acidosisMetabolic acidosis4.4. Hypothermic arrestHypothermic arrest5.5. Oxygen toxicityOxygen toxicity6.6. Reperfusion injuryReperfusion injury

44

1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENT

CNS complications from CPBCNS complications from CPB stroke = 1.5% (CABG) to 10% (valves)stroke = 1.5% (CABG) to 10% (valves) asymptomatic brain infarct by MRI = 18%asymptomatic brain infarct by MRI = 18%

• Floyd et al. 2006Floyd et al. 2006• Gerriets et al. 2010Gerriets et al. 2010

Sources of emboliSources of emboli atheroemboli from aortic manipulationatheroemboli from aortic manipulation thromboembolithromboemboli bubbles of air bubbles of air

• Raymond et al. 2001Raymond et al. 2001

55

1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTBrain Emboli: Brain Emboli: Cardiopulmonary Bypass Principles & PracticeCardiopulmonary Bypass Principles & Practice, Gravlee et al, Ed., 1993, pg 549, Gravlee et al, Ed., 1993, pg 549

66

1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTAir bubbles in the venous return lineAir bubbles in the venous return line

Wang S, Undar A . Vacuum-assisted venous drainage and gaseous microemboli in cardiopulmonary bypass. Wang S, Undar A . Vacuum-assisted venous drainage and gaseous microemboli in cardiopulmonary bypass.J Extra Corpor Technol. 2008 Dec;40(4):249-56.J Extra Corpor Technol. 2008 Dec;40(4):249-56.

77

1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTBlood emulsification with air by the vent and suckers:Blood emulsification with air by the vent and suckers:

Making bloody meringue!Making bloody meringue!

Ashby MF. The properties of foams and lattices. Philos Transact A Math Phys Eng Sci. 2006 Jan 15;364(1838):15-30.

Cheng KT. Air-filled, cross-linked, human serum albumin microcapsules. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2010. 2006 Jul 06 [updated 2008 May 08].

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1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTBorger MA, Feindel CM. Cerebral emboli during cardiopulmonary bypass: effect of perfusionist interventions and aortic cannulas. J Extra Corpor Technol Borger MA, Feindel CM. Cerebral emboli during cardiopulmonary bypass: effect of perfusionist interventions and aortic cannulas. J Extra Corpor Technol

2002; 34(1):29-33.2002; 34(1):29-33.

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1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTDealing with bubblesDealing with bubbles

Use an arterial filter/bubble trap w/ purgeUse an arterial filter/bubble trap w/ purge COCO22 flush the surgical field flush the surgical field

Add volume to the venous reservoirAdd volume to the venous reservoir Slow down the suckers and ventSlow down the suckers and vent Limit perfusionist interventionsLimit perfusionist interventions Use a circuit or MCA DopplerUse a circuit or MCA Doppler Ask the surgeon to stop what he is doing Ask the surgeon to stop what he is doing

and fix the bubble sourceand fix the bubble source Increase sweep FiOIncrease sweep FiO22

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1. NITROGEN ENTRAINMENT1. NITROGEN ENTRAINMENTConverting N2 bubbles in blood to O2 bubblesConverting N2 bubbles in blood to O2 bubbles

Vann RD, Butler FK, Mitchell SJ, Moon RE.Decompression illness. Lancet. 2011 Jan 8;377(9760):153-64.Vann RD, Butler FK, Mitchell SJ, Moon RE.Decompression illness. Lancet. 2011 Jan 8;377(9760):153-64.

Pre- Pre- oxygenator oxygenator

bubblebubble

Post- Post- oxygenator oxygenator

bubblebubble

Post-Post-oxygenator oxygenator

bubblebubble

Gas in the Gas in the bubblebubble FiO2 = 21%FiO2 = 21% FiO2 = 40%FiO2 = 40% FiO2 = 100%FiO2 = 100%

N2N2 70%70% 54%54% 0%0%

O2O2 19%19% 35%35% 89%89%

CO2CO2 5%5% 5%5% 5%5%

H2OH2O 6%6% 6%6% 6%6%

1111O2 radial vectors

r

R

Capillary radius: r = 5µCapillary X-section : A = r 2 = 78. 5 µ2

Cylinder radius: R = 10Cylinder X-section: A = R2 = 314 µ2

Capillary X-section Cylinder X-section

Ratio: = 1/4

paO2 = 80 mmHg pvO2 = 40 mmHg

Avg. ptO2 = 20 mmHg

Avg. ptO2 = 10 mmHg

Blood Flow

Understanding The Oxygen Pressure Field: Understanding The Oxygen Pressure Field: Krogh Cylinder ModelKrogh Cylinder Model

Highest ptO2: 79 mmHg Lowest ptO2: 1 mmHgOPF Range: 79 ~ 1 mmHg

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High PCD:Multiple capillary units

Low PCD:Single capillary unit

RESTING MUSCLE WORKING MUSCLEIncreasing PCD

Closed capillary unit

R R

Decreasing PCD

NORMAL ORGAN FUNCTION

ORGAN SHOCK

PERFUSED CAPILLARY DENSITY (PCD)PERFUSED CAPILLARY DENSITY (PCD)

1313

O2 radial vectors

1 mmHg pO2 line

1 mmHg pO2 line

ANOXIC LETHAL CORNER

ANOXIC LETHAL CORNER

paO2 = 80mmHg pvO2 = 40 mmHg

Highesttissue pO2:79mmHg

Anoxictissue

Capillary radius: r = 5µCapillary X-section : A = r 2 = 78. 5 µ2

Cylinder radius: R = 20Cylinder X-section: A = R2 = 1256 µ2

Ratio: Capillary X-section Cylinder X-section = 1/16

r

R

Blood Flow

1414

2. HEMODILUTION2. HEMODILUTIONShould Perfusionists Use A Transfusion TriggerShould Perfusionists Use A Transfusion Trigger

On Cardiopulmonary Bypass?On Cardiopulmonary Bypass?

Patients with ≥ 25% Hct = 2% mortality.Patients with ≥ 25% Hct = 2% mortality. Patients with ≤ 19% Hct = 4% mortality.Patients with ≤ 19% Hct = 4% mortality.

• DeFoe et al. 2001.DeFoe et al. 2001.

Should 19% be a trigger point?Should 19% be a trigger point? Reduce the mortality from 4% to 2%Reduce the mortality from 4% to 2%

NNT: Transfuse 90/100 low hematocrit patientsNNT: Transfuse 90/100 low hematocrit patients 2 additional patients survive2 additional patients survive 88 patients unnecessarily transfused88 patients unnecessarily transfused

• Grist G. AmSECT Today 2009.Grist G. AmSECT Today 2009.

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2. HEMODILUTION2. HEMODILUTIONCounter-acting Hemodilution With HyperoxiaCounter-acting Hemodilution With Hyperoxia

Hyperoxia use in non-cardiac surgeryHyperoxia use in non-cardiac surgery

SafeSafe• No adverse side effects (human experience)No adverse side effects (human experience)

Habler et al. 2002Habler et al. 2002

Reduces the need for transfusionReduces the need for transfusion• Less allogenic blood given (human experience)Less allogenic blood given (human experience)

Kemming et al. 2003Kemming et al. 2003

Preserves myocardial oxygenation during low hematocritPreserves myocardial oxygenation during low hematocrit• Reverses anemic hypoxic ECG changes (human experience)Reverses anemic hypoxic ECG changes (human experience)• Increases sub-endocardial O2-delivery 24% (animal study)Increases sub-endocardial O2-delivery 24% (animal study)

Kemming et al. 2004Kemming et al. 2004

Reverses tissue hypoxia at low hematocritReverses tissue hypoxia at low hematocrit• Tissue pO2 increases from 10 to 18 mmHg (animal study)Tissue pO2 increases from 10 to 18 mmHg (animal study)

Meier et al. 2004Meier et al. 2004

Reduces risk of wound infectionReduces risk of wound infection• Supplemental O2 (80% vs 30%) reduces infections by 39% (human experience)Supplemental O2 (80% vs 30%) reduces infections by 39% (human experience)

Brasel et al. 2005Brasel et al. 2005

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O2 Radial Vectors

1 mmHg tissue pO2line

paO2 = 150 mmHg

O2 Axial Vectors

2. HEMODILUTIONFormation Of An Anoxic Lethal Corner Due To Low Hematocrit

Anoxic TissuesLethal Corner Forms

Low Hct

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Augmented O2 Radial Vectors

Potential Lethal Corner Line

paO2 = 400 mmHg

Augmented O2 Axial Vectors

2. HEMODILUTIONAugmented Axial Vectors (Hyperoxia) Redistributes O2 To Prevent

An Anoxic Lethal Corner

Low Hct

Tissues OxygenatedLethal Corner Obliterated

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High PCD:Multiple capillary units

Low PCD:Single capillary unit

RESTING MUSCLE WORKING MUSCLE

Increasing PCDClosed capillary unit

R R

Decreasing PCD

NORMAL ORGAN FUNCTION

SHOCK

3. METABOLIC ACIDOSIS3. METABOLIC ACIDOSISPoor perfusion = decreased perfused capillary density (PCD)Poor perfusion = decreased perfused capillary density (PCD)

causing tissue anoxiacausing tissue anoxia

1919O2 radial vectors

CO2 radialvectors

paO2 = 100mmHgSAO2 = 99%

pvO2 = 40 mmHgSVO2 = 75%

paCO2 = 40 mmHg pvCO2 = 45 mmHg

Highesttissue pO2:99mmHg

Lowesttissue pCO2:

42mmHg

Lowesttissue pO2:

1mmHg

Highesttissue pCO2:

47mmHg

3. METABOLIC ACIDOSIS3. METABOLIC ACIDOSISNormal Capillary ConfigurationNormal Capillary Configuration

Blood Flow

2020O2 radial vectors

CO2 radialvectors

paO2 = 100mmHgSAO2 = 99%

pvO2 = 40 mmHgSVO2 = 75%

paCO2 = 40 mmHg pvCO2 = 60 mmHg

3. METABOLIC ACIDOSIS3. METABOLIC ACIDOSISCapillary Configuration In The Shock PatientCapillary Configuration In The Shock Patient

Blood Flow

Anoxic &/or Hypercapnic Lethal Corner

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ANOXIC LETHAL CORNER

Blood Flow

3. METABOLIC ACIDOSISPoor Perfusion = Decreased Perfused Capillary Density Causing

Tissue Anoxia

paO2 = 150 mmHg

O2 RADIAL VECTORS O2 AXIAL VECTORS

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AUGMENTED O2 RADIAL VECTORS

NO ANOXIC LETHAL CORNER

paO2 = 500 mmHg

r

R

Blood Flow

3. METABOLIC ACIDOSISAxial Kick = Oxygen Redistributed To The Lethal Corner

AUGMENTED O2 AXIAL VECTORS

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MANIPULATING AXIAL GRADIENTS:EFFECT OF PAO2 CHANGES ON BASE

BALANCE OVER FORTY HOURSIN A PRE-OP CDH PATIENT

0

20

40

60

80

100

120

140

160

180

200

1

AR

TE

RIA

L P

O2

-10

-8

-6

-4

-2

0

2

4

6

8

10

BA

SE

CH

AN

GE

, %

FIO

2 C

HA

NG

E

PAO2 BASE FIO2 Poly. (PAO2) Poly. (BASE)

FiO2 = 50%

FiO2 = 42%

FiO2 = 45%

FiO2 = 52%

FiO2 = 50%

FiO2 = 46%

3. METABOLIC ACIDOSIS3. METABOLIC ACIDOSIS

2424

Augmented O2 Radial Vectors

Potential 1 mmHg tissue pO2line

paO2 = 150 mmHg

Augmented O2 Axial Vectors

3. METABOLIC ACIDOSISAxial Kick Keeps Potential Lethal Corner OxygenatedAxial Kick Keeps Potential Lethal Corner Oxygenated

2525

O2 Radial Vectors

1 mmHg tissue pO2line

paO2 = 100 mmHg

Reduced O2 Axial Vectors

3. METABOLIC ACIDOSISReduced Axial Kick Causes Formation Of A Lethal CornerReduced Axial Kick Causes Formation Of A Lethal Corner

With Development Of A Base DeficitWith Development Of A Base Deficit

Lethal Corner Forms:Anoxic tissue

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4. HYPOTHERMIC ARREST4. HYPOTHERMIC ARRESTProfound Hypothermic Bypass And Circulatory Arrest:Profound Hypothermic Bypass And Circulatory Arrest:

The Need for Dissolved OxygenThe Need for Dissolved Oxygen Hemodilution reduces DO2Hemodilution reduces DO2 Hypothermia & alpha stat Hypothermia & alpha stat

impairs O2 off loadingimpairs O2 off loading Hyperoxia provides dissolved Hyperoxia provides dissolved

O2O2 ““Dissolved oxygen satisfies most Dissolved oxygen satisfies most

of the brain's oxygen requirements of the brain's oxygen requirements during profound hypothermic during profound hypothermic cardiopulmonary bypass.” cardiopulmonary bypass.”

• Dexter et al. 1997Dexter et al. 1997

““Used prior to DHCA normoxic Used prior to DHCA normoxic CPB increases brain damage CPB increases brain damage compared to hyperoxic CPB. The compared to hyperoxic CPB. The mechanism is hypoxic injury, mechanism is hypoxic injury, which overwhelms any injury which overwhelms any injury caused by oxygen free radicals.”caused by oxygen free radicals.”

• Nollert et al. 1999Nollert et al. 1999

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200 250 300 350 400 450 500 550 600 650 700 750 800 850 900

50 125 150 175 200 225 250 275 300 325 350 375 400 425 450 475

100 150 175 200 225 250 275 300 325 350 375 400 425 450 475 500

150 200 225 250 275 300 325 350 375 400 425 450 475 500 525

200 250 275 300 325 350 375 400 425 450 475 500 525 550

250 300 325 350 375 400 425 450 475 500 525 550 575

300 350 375 400 425 450 475 500 525 550 575 600

350 400 425 450 475 500 525 550 575 600 625

400 450 475 500 525 550 575 600 625 650

450 500 525 550 575 600 625 650 675

500 550 575 600 625 650 675 700

ARTERIAL PO2 MMHG

VE

NO

US

PO

2 M

MH

G

ESTIMATED AVERAGE TISSUE PO2

4. HYPOTHERMIC ARREST4. HYPOTHERMIC ARRESTBypass Hypothermia To Oxygen Load TissuesBypass Hypothermia To Oxygen Load Tissues

2828

Safe Arrest Time vs. Temperature by Tissue PO2Adult MET = 3.5 cc/kg/min @ 37°C

0

5

10

15

20

25

30

35

40

45

50

55

60

10 12 14 16 18 20 22 24 26 28 30

Temperature (°C)

Cer

ebra

l Saf

e A

rres

t T

ime

(min

)

525 mmHg

425 mmHg

325 mmHg

225 mmHg

125 mmHg

4. HYPOTHERMIC ARREST4. HYPOTHERMIC ARRESTCirculatory Arrest: Extending The Safe Arrest TimeCirculatory Arrest: Extending The Safe Arrest Time

Adult Brain MET @ 18°C = 0.7 cc/kg/min

2929

4. HYPOTHERMIC ARRESTPerfused Capillary Density (PCD): alpha stat vs. pH stat

High PCD:Multiple capillary units

Low PCD:Single capillary unit

Increasing PCD

Closed capillaries

R R

Alpha stat:1. systemic vasoconstriction2. reduced PCD3. low CO2 (relative alkalosis)4. oxyhemoglobin unloading

inhibited

pH stat:1. systemic vasodilation2. increased PCD3. high CO2 (relative acidosis)4. oxyhemoglobin unloading promoted

High PCD and high CO2 enhances tissue oxygen loading

prior to deep hypothermic circulatory arrest

Open capillaries

3030

4. HYPOTHERMIC ARREST4. HYPOTHERMIC ARRESTAcid Produced During 60 Minutes Arrest @ 18Acid Produced During 60 Minutes Arrest @ 18CC

0

5

10

15

20

25

30

Alpha statNormoxia

pH statNormoxia

Alpha statHyperoxia

pH statHyperoxia

[H+]

Nan

oequ

iv/L

Normoxia = pvO2 <150 mmHg

Hyperoxia = pvO2 > 300 mmHg

Pearl, Grist et al. 2000.

3131

Oxygen Toxicity vs Reperfusion InjuryOxygen Toxicity vs Reperfusion Injury

Oxygen toxicityOxygen toxicity normal capillary blood flownormal capillary blood flow intracellular pH normalintracellular pH normal active antioxidantsactive antioxidants too much Otoo much O22

Reperfusion injuryReperfusion injury poor capillary blood flowpoor capillary blood flow intracellular pH changeintracellular pH change deactivated antioxidantsdeactivated antioxidants reperfusion of capillaries & tissuesreperfusion of capillaries & tissues injury increases w/ Oinjury increases w/ O2 2 increaseincrease

AOX = antioxidantsROS = reactive oxygen species

3232

5. OXYGEN TOXICITY5. OXYGEN TOXICITYOff Gassing To Remove Nitrogen From Microemboli In The BodyOff Gassing To Remove Nitrogen From Microemboli In The Body

And Resetting The “Oxygen Clock”And Resetting The “Oxygen Clock”

PRESSURETIME (min)

MEDIApO2

mmHgpN2

mmHg

TOTAL TIME

(hrs:min)

3 ATM 20 100% O2 2280 0 0:20

3 ATM 5 AIR 479 1801 0:25

3 ATM 20 100% O2 2280 0 0:45

3-2 ATM 30 100% O2 2280 - 1520 0 1:15

2 ATM 5 AIR 319 1201 1:20

2 ATM 20 100% O2 1520 0 1:40

2 ATM 5 AIR 319 1201 1:45

2-1 ATM 30 100% O2 1520 - 760 0 2:15

US NAVY TREATMENT TABLE 5 - OXYGEN TREATMENT OF TYPE 1 DECOMPRESSION SICKNESS

““Because of the effective defense Because of the effective defense systems systems (functioning antioxidants),(functioning antioxidants), the tolerance of viable human cells the tolerance of viable human cells to to (reactive oxygen species)(reactive oxygen species) is is relatively high.”relatively high.” Bauer & Bauer. 1999Bauer & Bauer. 1999

USN uses 100% O2 to off gas N2 USN uses 100% O2 to off gas N2 causing decompression sicknesscausing decompression sickness

Oxygen toxicity prevented by five Oxygen toxicity prevented by five minute ‘air breaks’ taken minute ‘air breaks’ taken intermittently restore antioxidant intermittently restore antioxidant reserve capacityreserve capacity

Air breaks reduce CNS and Air breaks reduce CNS and

pulmonary complications.pulmonary complications. U.S Navy Diving Manual. 1991U.S Navy Diving Manual. 1991

Take away lesson for perfusionists: RTake away lesson for perfusionists: Reset the oxygen clock and reduce the potential for cardiac oxygen toxicity or reperfusion injury by reducing FiO2 prior to cross clamp removal.

3333

5. OXYGEN TOXICITY5. OXYGEN TOXICITYNeurologic Complication Comparison:Neurologic Complication Comparison:

CPB vs. Hyperbaric HyperoxiaCPB vs. Hyperbaric Hyperoxia

CNS complications from CPBCNS complications from CPB stroke = 1.5% (CABG) to 10% (valves)stroke = 1.5% (CABG) to 10% (valves) asymptomatic brain infarct (MRI) = 18%asymptomatic brain infarct (MRI) = 18%

• Floyd et al. 2006 Floyd et al. 2006

Hyperbaric hyperoxiaHyperbaric hyperoxia pO2 = 1520 mmHg (2 atm) to 2280 mmHg (3 atm) for 1 to 10 pO2 = 1520 mmHg (2 atm) to 2280 mmHg (3 atm) for 1 to 10

hours: decompression sickness, wound healing, infection, hours: decompression sickness, wound healing, infection, CO poisoning, radiation injury/necrosis, tissue grafts, burnsCO poisoning, radiation injury/necrosis, tissue grafts, burns

CNS event < 0.01%CNS event < 0.01%• Neumeister. 2008Neumeister. 2008

The risk of stroke is 150 - 1800 times greater during The risk of stroke is 150 - 1800 times greater during CPB than during hyperbaric hyperoxiaCPB than during hyperbaric hyperoxia

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6. REPERFUSION INJURY6. REPERFUSION INJURYMyocyte Cell Death By Ischemic Anoxia And Subsequent Myocyte Cell Death By Ischemic Anoxia And Subsequent

Reperfusion (Reoxygenation) Reperfusion (Reoxygenation)

Becker. 2004O2 off for 4 hours: 14% mortality

O2 off for 1 hr: 0% mortality

21% O2 on for 3 hr: 60% mortality

Control Group

Experimental Group

3535

6. REPERFUSION INJURY6. REPERFUSION INJURYReperfusion Injury Potential (RIP)Reperfusion Injury Potential (RIP)

Acronym for “Rest In Peace”Acronym for “Rest In Peace” RIP: the RIP: the hiddenhidden risk of a lethal reperfusion injury risk of a lethal reperfusion injury

upon the sudden reperfusion of ischemic tissues, upon the sudden reperfusion of ischemic tissues, i.e., the presence of a lethal corner.i.e., the presence of a lethal corner.

Shock: inadequate blood flow = poor tissue Shock: inadequate blood flow = poor tissue oxygenation & CO2 removaloxygenation & CO2 removal

CardiogenicCardiogenic SepticSeptic TraumaticTraumatic Hypovolemic septicHypovolemic septic NeurogenicNeurogenic

Shock: a state of insufficient perfusion that holds Shock: a state of insufficient perfusion that holds the the potential for reperfusion injurypotential for reperfusion injury if normothermic if normothermic oxygenation is suddenly restored.oxygenation is suddenly restored.

Low CPB flow at normothermiaLow CPB flow at normothermia Transplanted organsTransplanted organs

A cause of acute organ failure in transplants.

3636

6. REPERFUSION INJURY6. REPERFUSION INJURYECPR Hemodilution/Hypothermia To Prevent Reperfusion InjuryECPR Hemodilution/Hypothermia To Prevent Reperfusion Injury

Patients develop RIP during resuscitationPatients develop RIP during resuscitation Hypothermia reduces O2 needHypothermia reduces O2 need Hemodilution reduces oxygen delivery to Hemodilution reduces oxygen delivery to

tissuestissues Allows high blood flow without excessive Allows high blood flow without excessive

O2 delivery to facilitate CO2 removal.O2 delivery to facilitate CO2 removal.

Capillaries damaged during reperfusionCapillaries damaged during reperfusion Reduced viscosity counters ‘no reflow’ Reduced viscosity counters ‘no reflow’

phenomenon (aka DIC)phenomenon (aka DIC)

http://www.thoracic.org/sections/clinical-information/critical-care/critical-care-research/animal-models-of-acute-lung-injury.html

Normal mouse lungMouse lung after gastric ischemic/hypoxia reperfusion

www.benbest.com/cryonics/ischemia.html

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6. Reperfusion Injury6. Reperfusion InjuryPerfusionists need to identify patients at risk for reperfusion injury on CPBPerfusionists need to identify patients at risk for reperfusion injury on CPB

““Hyperoxemic (Hyperoxemic (paO2 ~ 400 mmHg)paO2 ~ 400 mmHg) cardiopulmonary bypass… did not produce cardiopulmonary bypass… did not produce oxidant damage or reduce functional recovery oxidant damage or reduce functional recovery after cardiopulmonary bypass in after cardiopulmonary bypass in non-hypoxemicnon-hypoxemic controls….“In contrast, controls….“In contrast, abrupt and gradual abrupt and gradual reoxygenationreoxygenation (of pre-CPB hypoxemic (of pre-CPB hypoxemic subjects)...subjects)...produced significant lipid peroxidation, produced significant lipid peroxidation, lowered antioxidant reserve capacity and lowered antioxidant reserve capacity and decreased functional recovery.”decreased functional recovery.”

Ihnken et al. 1995 Ihnken et al. 1995