Oxygen Transport: A Clinical Review Burn-Trauma-ICU Adults & Pediatrics Bradley J. Phillips, M.D.

Oxygen Transport:A Clinical Review

Burn-Trauma-ICUAdults & Pediatrics

Bradley J. Phillips, M.D.

“The First Concern”

“the first concern in any life-threatening illness

is to maintain

an adequate supply of oxygen

to sustain oxidative metabolism”

[Marino 2nd ed.]

Context

• The human adult has a vascular network that stretches over 60,000 miles– More than twice the circumference of the earth

• 8,000 liters of blood pumped per day

• Principle of Continuity– Conservation of mass in a closed hydraulic system– “the volume flow of blood is and must be the same at

all points throughout the circuit”

Flow Velocity & Cross-sectional Area

Respiratory Gas Transport

• Respiratory function of blood

• Dual system– Transport & delivery of oxygen TO the tissues

– Transport & delivery of carbon dioxide FROM the tissues

• Oxygen is the most abundant element on the surface of this planet…yet it is completely unavailable to the cells on the interior of the human system– the body, itself, acts as its own natural barrier…

– Why ? (remember…oxygen-metabolites are toxic)

Oxygen Radicals

The metabolism of oxygen occurs at

the very end of the

electron transport pathway

i.e. oxidative phosphorylation within

the mitochondrial body

Antioxidant TherapySelenium(glu. Peroxidase)

Glutathione(acts via reduction)

N-acetylcysteine(a glutahione analog)

Vit. E(blocks lipid peroxidation)

Vit. C(pro-oxidant to maintain iron as Fe(II)

Aminosteroids(? lipid peroxidation)

the transport system for oxygen is separated into 4 components:

taken together, these

form the “oxygen transport variables”

The Oxygen Transport Variables

• Oxygen Content [CaO2]

• Oxygen Delivery [DO2]

• Oxygen Uptake [VO2]

• Extraction Ratio [ER]

Oxygen Content (1)

the oxygen in the blood is either bound to hemoglobin

or dissolved in plasma

• the Sum of these two fractions is called the Oxygen Content

CaO2: the Content of Oxygen in Arterial Blood

Hb = Hemoglobin (14 g/dl)

SaO2 = Arterial Saturation (98 %)

PaO2 = Arterial PO2 (100 mmHg)

Oxygen Content (2)

CaO 2 = (1.34 x Hb x SaO2) + (0.003 x PaO2)

amount carried by Hb amount dissolved in plasma

CaO2 = (1.34 x 14 x 0.98) + (0.003 x 100)

CaO2 = 18.6 ml/dl (ml/dl = vol %; 18.6 vol %)

* at 100 % Saturation, 1 g of Hb binds 1.34 ml of Oxygen !

Oxygen Content (3)

• Note that the PaO2 contributes little to the Oxygen Content !

• Despite it’s popularity, the PaO2 is NOT an important measure of arterial oxygenation !

• The SaO2 is the more important blood gas variable for assessing the oxygenation of arterial blood !

the PaO2 should be reserved for evaluating the efficiency of pulmonary gas exchange

Hemoglobin vs. PaO2: CaO2

“the trifecta”

• Arterial oxygenation is based on 3 (and ONLY 3) things:– Hb– SaO2

– PaO2

• A 50% reduction in Hb leads to a direct 50% reduction in CaO2

• A 50% reduction in PaO2 leads to a 20% reduction in CaO2

CaO2: why do we so often forget ?

PaO2 influences oxygen content only to the extent that it influences

the saturation of hemoglobin

Hypoxemia (i.e. a decrease in PaO2) has a relatively SMALL impact

on arterial oxygenation if the accompanying change

in SaO2 is small !

Oxygen Content (4)

35 yr old male s/p GSW to Chest

Pulse 126 BP 164 / 72 RR 26

Hb = 12

Hct = 36

ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat

Question: What is this

Patient’s Oxygen Content ?

Oxygen Content (5)


Pulse 126 BP 164 / 72 RR 26Hb = 12Hct = 36


Oxygen Content:

CaO2 = (1.34 x Hb x SaO2)

CaO2 = ……..

Oxygen Delivery (1)

DO2: the Rate of Oxygen Transport in the Arterial Blood

* it is the product of Cardiac Output & Arterial Oxygen Content

DO2 = Q x CaO2

Cardiac Output, Q, can be “indexed” to body surface area

Normal C.I. : 2.5 - 3.5 L/min-m2

Bu using a factor of 10, we can convert vol % to ml/min

Oxygen Delivery (2)

DO2 = Q x CaO2

DO2 = 3 x (1.34 x Hb x SaO2) x 10

DO2 = 3 x (1.34 x 14 x .98) x 10

DO2 = 551 ml/min

Normal Range (CO): 800 – 1000 ml/min

Normal Range (CI) : 520 - 720 ml/min/m2

Oxygen Delivery (3)


Pulse 126 BP 164 / 72 RR 26

H/H = 12/36


CO = 4.8 CI = 2.1

Question: What is this

Patient’s Oxygen Delivery ?

Oxygen Delivery (4)


Pulse 126 BP 164 / 72 RR 26H/H = 12/36ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % SatCO = 4.8 (CI = 2.1)

Oxygen Delivery:DO2 = Q x CaO2 x 10DO2 = ……

Oxygen Uptake (1)

oxygen uptake is the final step

in the oxygen transport pathway and it represents the oxygen supply

for tissue metabolism

The Fick Equation:Oxygen Uptake is the Product of Cardiac Output

and

the Arteriovenous Difference in Oxygen Content

VO2 = Q x [(CaO2 - CvO2)]

Oxygen Uptake (2)

Oxygen Uptake (3)

The Fick Equation:

VO2 = Q x (CaO2 - CvO2)

VO2 = Q x [(1.34 x Hb) x (SaO2 - SvO2) x 10]

VO2 = 3 x [ (1.34 x 14) x (.98 - .73) x 10 ]

VO2 = 3 x [ 46 ]

VO2 = 140 ml/min/m2

Normal VO2: 110 - 160 ml/min/m2

Oxygen Uptake (4)

35 yr old male s/p GSW to ChestPulse 126 BP 164 / 72 RR

26Hb/Hct = 12/36


CO 4.8

SvO2 56 %

Question: What is this Patient’s Oxygen Uptake ?

Oxygen Uptake (4)


Pulse 126 BP 164 / 72 RR 26Hb/Hct = 12/36ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % SatCO 4.8 (CI 2.1)SvO2 56 %

Oxygen Uptake:VO2 = Q x (CaO2 - CvO2)VO2 = Q x [(1.34 x Hb) x (SaO2 - SvO2) x 10]VO2 = …….

Extraction Ratio (1)

the fractional uptake of oxygen

from the capillary bed

O2ER: derived as the Ratio of Oxygen Uptake to Oxygen Delivery

O2ER = VO2 / DO2 x 100

O2ER = 130 / 540 x 100 Normal Extraction

O2ER = 24 % 22 - 32 %


35 yr old male s/p GSW to ChestPulse 126 BP 164 / 72 RR

26H/H= 36


C0 4.8

SvO2 71 %

Question: What is this Patient’s Extraction Ratio ?



Pulse 126 BP 164 / 72 RR 26H/H= 36ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % SatC0 4.8SvO2 71 %

Extraction Ratio:O2ER = VO2 / DO2 x 100O2ER = …..


Questions:

1. ER = 16 %, what does this imply ?

2. ER = 42 %, what does this imply ?

Control of Oxygen Uptake

the uptake of oxygen from the microcirculation is a

set point that is maintained by adjusting the

Extraction Ratio

to match changes in oxygen delivery

the ability to adjust

O2 Extraction

can be impaired in serious illness

The Normal Response: O2ER (1)

The Normal Response to a

Decrease in Blood Flow is an Increase in O2 Extraction

sufficient enough to keep VO2 in the normal range

VO2 = Q x Hb x 13.4 x (SaO2 - SvO2)

• Q = 3; VO2 = 3 x 14 x 13.4 x (.97 - .73) = 110 ml/min

• Q = 1; VO2 = 1 x 14 x 13.4 x (.97 - .37) = 109 ml/min

The Normal Response: O2ER (2)

• The Drop in Cardiac Index is BALANCED by an

Increased (SaO2 - SvO2) Difference…and VO2 remains Unchanged

• Note the drop in SvO2 from 97 % to 37 % !!

• This association between SvO2 & O2ER is the Basis for SvO2 Monitoring

The Ability to Adjust Extraction is a feature of all vascular beds except the Coronary Circulation & the Diaphragm !

The DO2 - VO2 Curve (1)


• As O2 delivery decreases below normal, the ER increases proportionally to keep VO2 constant

• When ER reaches its maximum level (50 – 60%), further decreases in DO2 are accompanied by proportional decreases in VO2

• Critical DO2

– The DO2 at which consumption becomes supply-dependent– The point at which energy production within the cell becomes

oxygen-limited


• Flat Portion of the Curve– VO2 Flow - Independent

– O2 Extraction varies in response to Blood Flow (VO2 Constant)

• Linear Portion of the Curve– VO2 Flow - Dependent

– Indicates a defect in oxygen extraction from the microcirculation

– Extraction is fixed and VO2 becomes directly dependent on Delivery

• Critical Level of Oxygen Delivery – The Threshold DO2 needed for Adequate Tissue Oxygenation

– If DO2 falls below this level, oxygen supply will be sub-normal

“In the ICU…”

The critical DO2 in anesthesized patients is around 300 ml/min.

However, in critically-ill patients, the Critical DO2 varies widely from 150 – 1000 ml/min…

[Leach et al. Dis Mon. 1994;30:301-368]

Mixed Venous Oxygen

By rearranging the Fick Equation, the determinants of Venous Oxygen are:

VO2 = Q x Hb x 13 x (SaO2 - SvO2)

SvO2 = SaO2 - (VO2/Q x Hb x 13)

* the most prominent factor in determining SvO2 is VO2/Q

Causes of a Low SvO2: Hypoxemia

Increased Metabolic Rate

Low Cardiac Output

Anemia

Remember: Mixed Venous

In Critically-Ill Patients, augmenting the extraction ratio (in response to a change in oxygen delivery)

may not be possible !

In these patients, the Venous Oxygen Levels may change little in response to changes in Cardiac Output !

thus, the Relationship between CO (Q) and Mixed Venous Oxygen must be

determined before using SvO2 or PvO2 to monitor changes in DO2 or VO2

Oximetry

Arterial Oxygen Saturation can be estimated but Venous Oxygen Saturation

MUST be Measured !

• Due to the shape of the Oxyhemoglobin Curve

• The arterial Sat falls on the flat portion & can be safely estimated

• The venous Sat (68 - 77 %) falls on the Steep Portion and can vary significantly even with small errors in estimation !

OxyHb Curve (1)

•“Rule-of-Dennis-Betting”

• 50 % Sat…PO2 25

•Mixed Ven. Sat 75…PO2 40

OxyHb Curve (2)

“Right-shift: off-loading”

• Acidosis

• Elevated temperature

• Elevated CO2

• Increased 2,3-DPG

Carbon Dioxide (1)

An increase in PCO2 of 5 mmHg can result in a twofold increase in minute ventilation…

to produce the same increment in ventilation,

the PaO2 must drop to 55 mmHg

The ventilatory control system keeps a close eye on

CO2 but pays little attention to PaO2…while clinicians keep a close eye on PaO2

and pay little attention to PCO2

“I just don’t understand….”

Carbon Dioxide (2)

• The CO2 “Sink”

• Ready source of ions (H+ & HCO3

-)

Buffering capacity of Hb

(6x that of all the plasma

proteins combined)

CO2 Extraction

The Respiratory Quotient

RQ = VCO2 / VO2

• VCO2 normally 10 mEq/min (14,400 mEq/24 hrs)

• Exercise: lung excretion can reach 40,000 mEq/24 hrs.

• The kidneys normally excrete 40 – 80 mEq acid /24 hrs

Tissue O2-Balance

• Oxygen supply to the tissues is the rate of O2 uptake from the microcirculation– VO2 & ER

• The metabolic requirement for oxygen is the rate at which oxygen is metabolized to water within the mitochondria– MRO2

• Because oxygen is NOT stored in the tissues, VO2 must match MRO2 if aerobic metabolism is to continue

when matching occurs, glucose is completely oxidized to yield 36 moles of ATP

Oxygen Balance

when matching occurs, glucose is completely

oxidized to yield 36 moles of ATP

• When matching is not equal (VO2 is less than MRO2), a portion of the glucose is diverted to the production of lactate in an attempt to salvage energy

• Per mole of glucose converted through anaerobic metabolism, 2 moles of ATP are gained (47 kcal)

Dysoxia

the condition in which the production of ATP

is limited by the supply of oxygen

when cell dysoxia leads to a measurable

change in organ function….SHOCK

VO2 & MRO2

VO2 Deficit

• In ICU patients, a VO2 that falls below the normal range (i.e. below 100 ml/min), can be used as evidence of impaired tissue oxygenation

• Studies have shown a direct relationship between the magnitude of the VO2 deficit and the risk of multiorgan failure

[Dunham et al. CCM 1991;19:231-243][Shoemaker et al. Chest 1992;102:208-215]

Oxygen Debt

The cumulative VO2

deficit is referred to as the

“oxygen debt”

In ICU patients, there may

be a progressive and linear

relationship between

VO2 & DO2

Monitoring of O2 Transport

The transport variables provide

no information

about the ADEQUACY of

tissue (cellular) oxygenation…

because that requires a measurement of

metabolic rate.

Interpreting the Transport Variables

• Low VO2:– Indicates a tissue oxygen deficit– “Oxygen Debt”

• The total VO2 deficit over time• Remember the direct relationship exists between magnitude of

the oxygen debt and subsequent risk of multiorgan failure

• Normal VO2:– Requires a blood lactate level to determine the

adequacy of global tissue oxygenation

Correcting a VO2 Deficit (1)

• Step 1: CVP or PWP– If low, infuse volume to normalize filling pressure

– If normal or high, go to step 2

• Step 2: CO– If low & filling pressures not optimal…infuse volume

– If low & filling pressures high, start DOBUTAMINE & titrate keep CI > 3 L/min/m2 (some believe 5)

• If blood pressure is also low, start DOPAMINE or LEVOPHED

– If CI > 3, proceed to Step 3.

Correcting a VO2 Deficit (2)

• Step 3: VO2 (Oxygen Uptake)– If VO2 is less than 100 ml/min/m2, use VOLUME

• to goal of CVP 8 – 12; PWP 18 – 20• inotropic therapy to achieve a CI > 4.5 L/min/m2

– Correct Hb if less than 8 g/dl (some say 10 g/dl)– If VO2 is greater than 100 ml/min/m2, proceed to Step 4.

• Step 4: Blood Lactate– Lactate > 4 with other signs of shock (i.e. organ failure, low BP), decrease

METABOLIC RATE – via sedation or paralysis (? Pentobarbital coma)– Lactate 2 – 4...controversial !– Lactate < 2…observe

VO2 & DO2 vs. Time

0

200

400

600

800

1000

1200

1400

1600

Admit 2 Hrs 12 Hrs 16 Hrs 18 Hrs 24 Hrs

VO2

DO2

Role of Serum Lactate (1)

• An elevated lactate indicates that VO2 is less than the metabolic rate

• The approach must then be to either decrease the metabolic rate or increase the VO2

achieving a supranormal level of VO2 may be difficult

and carries risks

Serum Lactate (2)

Aduen, et al. JAMA 1994;272:1678-1685

Serum Lactate & Cardiac Index

0

1

2

3

4

5

6

7

8

Admit 12 hrs 24 hrs 72 hrs

LactateC.I.

Serum Lactate & Cardiac Index

0

1

2

3

4

5

6

7

Admission 6 12 18 24

Lactate

C.I.

Optimizing Oxygen Transport: The Steps

Filling Pressures

Cardiac Output

VO2

Serum Lactate

Oxygen Transport Variables

Parameter Normal Range

Delivery (DO2) 500 - 800 ml/min

Uptake (VO2) 110 - 160 ml/min

Extraction Ratio (ER) 22 - 32 %

Mixed Venous PO2 33 - 53 mmHg

Mixed Venous SO2 68 - 77 %

** DO2 & VO2 can be indexed to body surface area

Oxygen Transport

“it would be a mostdifficult task

to explain”

Any Questions Yet ?

Oxygen Transport: Case 1 (1)

32 yr old male 6 hrs s/p GSW to the Abdomen

Hypotensive & “nearly coded” on the table…

Liver “shattered” & packed…

Multiple holes in the Small Bowel, Stomach, and Right Chest…

Packed and “whip-stitched closed” the fascia…

Now hypotensive and dropping her sats…

“what do you want to do ?”

Oxygen Transport: Case 1 (2)

Remember the Steps:

Filling Pressures…

Cardiac Output…

VO2…

Serum Lactate…

Questions…? The Oxygen Transport Variables

• Oxygen Content [CaO2]

• Oxygen Delivery [DO2]

• Oxygen Uptake [VO2]

• Extraction Ratio [ER]

Oxygen Transport: A Clinical Review Burn-Trauma-ICU Adults & Pediatrics Bradley J. Phillips, M.D.

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Transcript of Oxygen Transport: A Clinical Review Burn-Trauma-ICU Adults & Pediatrics Bradley J. Phillips, M.D.