Transcript Oxygen Transport

Oxygen Transport:
A Clinical Review
Burn-Trauma-ICU
Adults & 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 Therapy
Selenium
(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
Hb = 12
Hct = 36
BP 164 / 72
RR 26
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
Question: What is this
Patient’s Oxygen Content ?
Oxygen Content (5)
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
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
DO2
DO2
DO2
DO2
=
=
=
=
(2)
Q x CaO2
3 x (1.34 x Hb x SaO2) x 10
3 x (1.34 x 14 x .98) x 10
551 ml/min
Normal Range (CO): 800 – 1000 ml/min
Normal Range (CI) : 520 - 720 ml/min/m2
Oxygen Delivery
(3)
35 yr old male s/p GSW to Chest
Pulse 126
H/H = 12/36
BP 164 / 72
RR 26
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
CO = 4.8 CI = 2.1
Question: What is this
Patient’s Oxygen Delivery ?
Oxygen Delivery
(4)
35 yr old male s/p GSW to Chest
Pulse 126
BP 164 / 72
RR 26
H/H = 12/36
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
CO = 4.8 (CI = 2.1)
Oxygen Delivery:
DO2
=
Q x CaO2 x 10
DO2
=
……
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 Chest
Pulse 126
BP 164 / 72
RR 26
Hb/Hct = 12/36
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
CO 4.8
SvO2 56 %
Question: What is this
Patient’s Oxygen Uptake ?
Oxygen Uptake
(4)
35 yr old male s/p GSW to Chest
Pulse 126
BP 164 / 72
RR 26
Hb/Hct = 12/36
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
CO 4.8 (CI 2.1)
SvO2 56 %
Oxygen Uptake:
VO2
=
VO2
=
VO2
=
Q x (CaO2 - CvO2)
Q x [(1.34 x Hb) x (SaO2 - SvO2) x 10]
…….
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
O2ER = 24 %
Normal Extraction
22 - 32 %
Extraction Ratio
(2)
35 yr old male s/p GSW to Chest
Pulse 126
BP 164 / 72
RR 26
H/H= 36
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
C0 4.8
SvO2 71 %
Question: What is this
Patient’s Extraction Ratio ?
Extraction Ratio
(3)
35 yr old male s/p GSW to Chest
Pulse 126
BP 164 / 72
RR 26
H/H= 36
ABG’s: pH 7.38 / PaO2 100 / PaCO2 32 / 96 % Sat
C0 4.8
SvO2 71 %
Extraction Ratio:
O2ER
O2ER
=
=
VO2 / DO2 x 100
…..
Extraction Ratio
(3)
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)
The DO2 - VO2 Curve
(2)
• 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
The DO2 - VO2 Curve
(3)
• 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
The DO2 - VO2 Curve
(2)
“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
•“Rule-of-Dennis-Betting”
• 50 % Sat…PO2 25
•Mixed Ven. Sat 75…PO2 40
(1)
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
1600
VO2
1400
DO2
1200
1000
800
600
400
200
0
Admit
2 Hrs
12 Hrs
16 Hrs
18 Hrs
24 Hrs
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
Lactate
C.I.
8
7
6
5
4
3
2
1
0
Admit
12 hrs
24 hrs
72 hrs
Serum Lactate & Cardiac Index
7
6
Lactate
5
C.I.
4
3
2
1
0
Admission
6
12
18
24
Optimizing Oxygen Transport: The Steps
Filling Pressures
Cardiac Output
VO2
Serum Lactate
Oxygen Transport Variables
Parameter
Delivery (DO2)
Uptake (VO2)
Extraction Ratio (ER)
Mixed Venous PO2
Mixed Venous SO2
Normal Range
500 - 800 ml/min
110 - 160 ml/min
22 - 32 %
33 - 53 mmHg
68 - 77 %
** DO2 & VO2 can be indexed to body surface area
Oxygen Transport
“it would be a most
difficult 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]