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GRAPHICAL ANALYSIS OF SYSTOLIC PRESSURE VARIATIONS AND
RELATED NONINVASIVE INDICATORS OF BLOOD VOLUME STATUS.
by
Richard Stewart Shelton
A thesis submitted to the faculty of the University of Utah in partial fulfillment of the
requirements for the degree of
Masters of Science in Bioengineering
Department of Bioengineering
University of Utah
July 2002
Copyright © Richard Stewart Shelton 2002
All Rights Reserved
SUPERVISORY COMMITTEE APPROVAL FORM
FINAL READING APPROVAL FORM
ABSTRACT
Systolic Pressure Variation or SPV is a useful indicator of blood volume status.
SPV is characterized as an initial increase in systolic pressure followed by a subsequent
decrease in systolic pressure due to positive pressure ventilation. With blood loss, the
systolic pressure is further decreased and the overall variation in systolic pressure
increases.
SPV is similar to the variation of other indicators of blood volume status in that it
corresponds to a simultaneous variation in stroke volume. The cause of these variations
was studied through graphical analysis using different models of the circulation. These
models showed that positive intrathoracic pressure causes an initial increase in stroke
volume followed by a decrease in stroke volume, which causes the increase and decrease
in systolic pressure observed in SPV. However, these models were not able to predict a
greater decrease in stroke volume after blood loss. Therefore, a further decrease in the
systolic pressure was not predicted.
Nevertheless, some more recent studies of the compensation mechanisms of the
body affecting these models suggest that a further decrease in systolic pressure with
blood loss is possible. Currently, these compensation mechanisms are not well enough
understood to completely explain the further decrease in systolic pressure in SPV after
blood loss. Therefore, an animal study is proposed to better understand the compensation
mechanisms that cause the further decrease in systolic pressure with blood loss.
v
TABLE OF CONTENTS ABSTRACT………………………………………………………………………….….iv ACKNOWLEDGEMENTS……………………………………………………………..vi Chapter
I. SYSTOLIC PRESSURE VARIATIONS………………………………..1 II. PHOTO-PLETHYSMOGRAPHIC PULSE WAVEFORM VARIATIONS
……………………………………………………………………..…….7 III. CARDIOGENIC OSCILLATION VARIATION ……………………..10 IV. THE THEORY OF SPV ..………………………………………………15 V. ∆UP …………………………..………………………………………...17 VI. ∆DOWN……..………………………………………………………….21 Guyton’s Graphical Model …………………………………………….21 SPV is Caused by Positive Pressure Breaths .………………………….28 VII. SPV INCREASES WITH BLOOD LOSS ……………………………..30
The Effect of Blood Loss and Compensation Mechanisms on the Function Curves…………………………………………………………………..31
Will ∆down Increase with Blood Loss According to Guyton’s Model? ………………………………………………………………………….32 What Went Wrong?…………………………………………………….34
VIII. ADDITIONAL STUDIES OF PHOTO-PLETHYSMOGRAPHIC PULSE
WAVEFORM VARIATIONS……………………. …………………...38 IX. FURTHER WORK …………………………………………………….45 X. CONCLUSION………………………………………………..………..47
REFERENCES………………………………………………………………….………49
vi
ACKOWLEDGEMENTS
1
CHAPTER 1
SYSTOLIC PRESSURE VARIATIONS
What Is It?
Systolic Pressure Variation (SPV) is the variation in systolic blood pressure
during one positive pressure breath initiated by ventilation [1-13].
Figure 1. Systolic Pressure Variations (SPV). Perel A, Pizov R, Cotev S: Systolic blood
pressure variation is a sensitive indicator of hypovolemia in ventilated dogs subjected to
graded hemorrhage. Anesthesiology. 67: 499, 1987.
SPV is measured by first establishing a baseline systolic pressure during apnea
[1]. Then, after initiation of a positive pressure breath, the increase and decrease in
systolic pressure from this baseline is measured as ∆up and ∆down respectively [1].
2
Figure 2. ∆up and ∆down. Pizov R, Ya’ari Y, Perel A: Systolic pressure variation is
greater during hemorrhage than during sodium nitroprusside-induced hypotension in
ventilated dogs. Anesth Analg. 67:171, 1988.
In general, at the initiation of a positive pressure breath, the systolic pressure will
initially increase and ∆up is measured [1]. Then, within the same positive pressure
breath, the transient increase in systolic blood pressure is followed by a decrease in
systolic blood pressure below the baseline systolic blood pressure and ∆down is
measured [1].
Figure 3. Isolated breath with ∆up and ∆down. Perel A, Pizov R, Cotev S: Systolic
blood pressure variation is a sensitive indicator of hypovolemia in ventilated dogs
subjected to graded hemorrhage. Anesthesiology. 67: 499, 1987.
3
Measurement of SPV has been successfully used as a minimally invasive
indicator of blood volume status for over a decade [1-9]. Most of the initial successful
studies where SPV was used as an indicator of blood volume status were performed on
dogs [1-3]. In these studies done by Perel and associates, SPV was measured at normal
blood volume, and after blood loss of 5, 10, 20, and 30% of their estimated blood
volume. Then, SPV was measured again after retransfusion. As blood volume was
decreased, SPV and especially the ∆down portion of SPV, increased [1].
Figure 4. SPV at normal and decreased blood volume. Rooke GA, Schwid HA, Shapira
Y: The effect of hemorrhage and intravascular volume replacement on systolic pressure
variation in humans during mechanical and spontaneous ventilation. Anesth Analg. 80:
926, 1995.
In these first studies, increase in SPV was found to be a more accurate indicator
than other commonly used indicators of blood volume status [1-2]. Below are the results
of a study comparing SPV and ∆down with other indicators of blood volume status.
%SPV, shown below in the results, is the measured SPV divided by the systolic pressure
at apnea.
4
Figure 5. SPV Results. Perel A, Pizov R, Cotev S: Systolic blood pressure variation is a
sensitive indicator of hypovolemia in ventilated dogs subjected to graded hemorrhage.
Anesthesiology. 67: 501, 1987.
Similar studies have confirmed the usefulness of SPV in monitoring blood
volume status in varied circumstances [4-13]. Some studies have even demonstrated the
usefulness of automating the measurement of SPV where the systolic pressure at the end
of a positive pressure breath was approximated as the baseline blood pressure at apnea
[14].
5
Figure 6. Schwid study comparison of end-expiration pressure to apnea pressure.
Schwid HA, Rooke GA: Systolic blood pressure at end-expiration measured by the
automated systolic pressure variation monitor is equivalent to systolic blood pressure
during apnea. Journal of Clinical Monitoring and Computing. 16: 118, 2000.
As a partial explanation of the origin of these variations in systolic pressure, Perel
and associates performed a study in which they concluded that variations in systolic
pressure were closely related to variations in stroke volume [15]. Furthermore, these
decreases in systolic pressure in ∆down were accompanied by simultaneous decreases in
stroke volume [15]. These results imply that the variations in systolic pressure are a
direct result of the variations in stroke volume beat to beat. Below are the results
showing the correlation between the variations in systolic pressure and stroke volume
measured through velocity time index (VTI) detected by a doppler probe.
6
Figure 7. Correlation of SPV and Stoke Volume Variation or % change in VTI.
Beaussier M, Coriat P, Perel A, Lebret F, Kalfon P, Chemla D, Lienhart A, Viars P:
Determinants of systolic pressure variation in patients ventilated after vascular surgery.
Journal of Cardiothoracic and vascular anesthesia. 9(5):550, 1995.
7
CHAPTER 2
PHOTO-PLETHYSMOGRAPHIC PULSE WAVEFORM VARIATIONS
These variations in stroke volume can also be detected through monitoring
variations in other indicators of hemodynamics. One of these is photo-plethysmographic
pulse waveform variations (PWV) or the variations of the waveforms of pulse oximetry.
The first study to show the usefulness of PWV in monitoring blood volume was
performed by Partridge and associates [16]. They showed that an increase in PWV was a
sensitive indicator of blood loss or hypovolemia [16]. An example of the change in PWV
during blood loss and fluid resuscitation is shown below. After blood loss, PWV
increased; and after fluid resuscitation, the PWV decreased to near its original variation.
Figure 8. Examples of PWV in Partridge study. Partridge BL: Use of pulse oximetry as
a noninvasive indicator of intravascular volume status. J Clin Monit. 3: 265, 1987.
In addition, Perel and associates also found PWV to be effective as an indicator of
blood volume status [17]. PWV was measured by Perel and associates in a similar way
8
to SPV [17]. The photo-plethysmographic pulse waveform was first recorded during
apnea [17]. From this waveform the signal strength of the peak plateau was recorded as a
baseline [17]. Next, at the initiation of a positive pressure breath, the signal strength from
the maximal peak to the apneic plateau was measured as the ∆up [17]. Finally, the signal
strength from the minimal peak to the apneic plateau was measured as the ∆down [17].
An example of PWV compared to SPV during normal blood volume and during
hypovolaemia is shown below.
Figure 9. Examples of PWV in Shamir study. Shamir M, Eidelman LA, Floman Y,
Kaplan L, Pizov R: Pulse oximetry plethysmographic waveform during changes in blood
volume. British Journal of Anaesthesia. 82(2): 180, 1999.
The results of their studies matched closely with the results of SPV studies. They
show that PWV is an effective monitor of blood volume status.
However, PWV has several advantages over SPV. Because pulse oximetry is less
invasive and more commonly monitored than an arterial line, PWV is more convenient
and more readily available than SPV [16]. Also, PWV introduces less injury and risk to
9
the patients. For these reasons, we saw PWV as a practical method of automatically and
continuously monitoring blood volume status during surgery.
10
CHAPTER 3
CARDIOGENIC OSCILLATION VARIATION
Another method of noninvasively monitoring variations in stroke volume is to
monitor the flow signal waveform of the ventilator providing positive pressure ventilation
to the animal. Often in these waveforms, oscillations can be found that correspond to the
heart rate of the animal.
-60-50-40-30-20-10
010203040
0 2 4 6 8 10Time (sec)
Flo
w (
L/m
in)
Figure 10. Cardiogenic Oscillations.
These cardiogenic oscillations are the result of the heart pumping and creating a
negative pressure sufficient to suck air into the lungs during a positive pressure breath.
The magnitude of these oscillations was found to correlate well to stroke volume in our
lab by a fellow student, Kai Breuger. An example of the correlation between these
cardiogenic oscillations and stroke volume are shown below.
11
0.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
90.0
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45
indexstroke volume (ml of blood)
0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
air volume (ml of air)
Thermodilution
Cardiogenic Oscillations
y = 0 . 1 1 4 8 x + 0 . 6 7 5 9R 2 = 0 . 5 4 0 1
0 . 0 0
2 . 0 0
4 . 0 0
6 . 0 0
8 . 0 0
1 0 . 0 0
1 2 . 0 0
1 4 . 0 0
0 . 0 1 0 . 0 2 0 . 0 3 0 . 0 4 0 . 0 5 0 . 0 6 0 . 0 7 0 . 0 8 0 . 0 9 0 . 0
s t r o k e v o l u m e ( m l o f b l o o d )
air
volu
me
(ml o
f ai
r)
Figure 11. Correlation between cardiogenic oscillations and stroke volume.
Furthermore, in one dog, the variations in the heights of these cardiogenic
oscillations or cardiogenic oscillation variations (COV) were found to increase after
blood loss.
12
8480 8500 8520 8540 8560 8580 8600 8620
24
26
28
30
32
34
36
flow
d28jun99flow16005750 5800 5850 5900
24
26
28
30
32
34
36
Before Blood Loss After Blood Loss
Figure 12. COV before and after blood loss.
In fact, COV increased until approximately 50% of the estimated blood volume
were shed. The values of COV with the approximate blood loss are shown below.
Estimated % Blood Loss
0% 19% 27% 75%
Variation Mean StDev Mean StDev Mean StDev Mean StDev
in Height 0.7 2.0 1.5 1.5 3.1 0.81 2.4 0.78
Table 1. The height of the COV as blood is removed.
COV
01234
0% 20% 40% 60% 80%
% Estimated Blood Loss
Hei
gh
t o
f C
OS
(L
/min
)
Figure 13. The height of the COV as blood is removed.
Monitoring COV was attempted in many other dogs and pigs and even on the
flow signal waveforms of several humans but often times the cardiogenic oscillations in
13
these waveforms were not identifiable. An example is shown below of a pig flow signal
waveform compared to a dog flow signal waveform.
3300 3400 3500 3600 3700 3800-50
-40
-30
-20
-10
0
10
20
30
40
flow
p06oct99flow1200
2250 2300 2350 2400 2450 2500 2550 2600 2650-50
-40
-30
-20
-10
0
10
20
30
d28jun99flow1600
flow
Pig Flow Signal Dog Flow Signal
Figure 14. Pig and Dog flow signal.
As you can see, the cardiogenic oscillations are not very prominent. One possible
reason that the cardiogenic oscillations are not prominent is that pigs and humans have a
different ratio of lung compliance to chest compliance than dogs. In fact, Perel and
associates note that dogs have a greater chest compliance relative to their lung
compliance than humans [1]. Because chest compliance in dogs is greater relative to
lung compliance than in pigs and humans, the lungs are more easily influenced by the
negative pressures created by the pumping of the heart in dogs. Thus, the effects of the
pumping of the heart in pigs and humans do not cause a noticeable oscillation on the flow
signal.
One other problem with monitoring the cardiogenic oscillations of the pigs and
humans is that the ventilation scheme was different than the dog studies. First of all,
constant pressure ventilation was used instead of constant flow ventilation. Constant
flow ventilation is needed to provide a stable baseline from which to measure cardiogenic
14
oscillations. However, constant flow is becoming a less popular method of ventilation
for various reasons [18]. The second problem with the ventilation scheme was that the
tidal volumes were too large and introduced pressures in the lungs that overwhelmed the
cardiogenic oscillations.
So, in summary, although monitoring COV is completely noninvasive,
continuously available in surgery, and a promising method of monitoring blood volume,
the cardiogenic oscillations were often not identifiable or discernable. Perhaps, if a
ventilation scheme were used that employed smaller, more frequent tidal volumes with
constant flow, cardiogenic oscillations would be more often identifiable and useful for
monitoring blood volume status.
15
CHAPTER 4
THE THEORY OF SPV
What causes SPV and the variation of other indicators and why do they increase
with blood loss? Perel gives one explanation [5]. His explanation is based on the
influence of the positive pressure breaths on the preload and afterload of the right and left
ventricle respectively. First, the increased intrathoracic pressure of the positive pressure
breath hinders the blood from entering the right ventricle and decreases the preload of the
right ventricle [5]. Secondly, after the initiation of the positive pressure breath, the
resistance of the pulmonary vasculature increases and thereby increases the afterload of
the right ventricle [1,5]. Eventually, both of these effects serve to decrease the stroke
volume of the right ventricle after one or two beats of the heart.
Another effect of the positive pressure breath is that the positive pressure
squeezes the blood out of the lungs and into the left ventricle [1,5]. The extra blood in
the left ventricle increases the preload of the left ventricle and the left ventricle stroke
volume initially increases. In addition, the systolic wall stress increases and the aortic
impedance decreases [1,5]. These effects serve to decrease left ventricular afterload and
also provide for the initial increase in stroke volume. In Summary, these effects cause an
initial increase in left ventricular stroke volume followed by a decrease in stroke volume
after one or two beats.
Perel continues to explain that the increase in SPV after blood loss is caused by a
further dependence of stroke volume on preload after blood loss [1,5]. Therefore, when
16
preload is decreased by the positive pressure breaths, the decrease in stroke volume is
greater after blood loss. Thus, ∆down and SPV as a whole are increased.
These theories may all be true. However, they have never been tested by
scientific principles. First of all, an explanation based only on afterload and preload
depends on a number of questionable assumptions like constant twitch tension and
contractility for different preloads. They also ignore the role of the body’s vasculature in
providing venous return and preload to the right ventricle. In reality, the cardiac output
of the heart and the venous return of the vasculature are mutually dependent on each
other. Therefore, an adequate explanation of SPV should describe the effects of positive
pressure breaths on both the heart function and the vascular function.
In the following chapters, a graphical analysis of the occurrence of SPV and its
relationship to blood volume is attempted.
17
CHAPTER 5
∆UP
First, an explanation of ∆up is here supplied. ∆Up in particular represents a
transient increase in systolic pressure. Perel proved in his study of stroke volume
variation that the variation of systolic pressure in SPV is closely related to the variation
of stroke volume [15]. Thus, this transient increase in systolic pressure of ∆up followed
by a decrease in systolic pressure is indicative of a temporary augmentation of stroke
volume caused by a positive pressure breath. This augmentation is followed by a
decrease in stroke volume and systolic pressure that is representative of the steady state
response of the circulation to a positive pressure breath. The transient response of the
increased stroke volume can be explained by relating positive pressure breathing to
another study.
This study done by Bromberger-Barnea explains the transient response of the
circulation due to changes in intrathoracic pressure [19]. Bromberger-Barnea showed
that according to graphical analysis, a decrease in intrathoracic pressure causes a decrease
in stroke volume [19]. Bromberger-Barnea’s graphical analysis is shown below. The
first graph is a representation of a normal beat of the heart and the other three graphs are
representations of a beat of the heart under different negative intrathoracic pressures.
18
Figure 15. Bromberger-Barnea’s graphical analysis of decreased intrathoracic
pressure. Bromberger-Barnea B: mechanical effects of inspiration on heart functions: a
review. Federation Proc. 40: 2173, 1981.
Bromberger-Barnea then confirmed her analysis through experiments that
decreased the intrathoracic pressure and thus decreased the stroke volume [19]. The
results one of those experiments is shown below. As can be seen, the QAO or cardiac
output decreases with decreased intrathoracic pressure. This effect is not shown to be
transient here because the QPA or the cardiac output of the right heart is held constant.
19
Figure 16. Experiment confirming graphical analysis of decreased intrathoracic
pressure. Bromberger-Barnea B: mechanical effects of inspiration on heart functions: a
review. Federation Proc. 40: 2176, 1981.
Therefore, using a similar graphical analysis of increased intrathoracic pressure
shows that stroke volume should transiently increase with positive pressure breaths. A
graphical analysis of an increase in intrathoracic pressure of approximately 9-mmHg is
shown below.
20
0 20 40 60 80 100 1200
20
40
60
80
100
120
140
160
PL
V-P
PL
(m
mH
g)
LV VOL. (ml)
AA1BB1
C
C1
D
D1
Increase in SV = 7%
PLAM = 7.2mm Hg
Increased Intrathoracic Pressure
Figure 17. Graphical analysis of increased intrathoracic pressure.
This graph shows an increase of stoke volume of approximately 7% with an
increase in intrathoracic pressure of approximately 9-mmHg. This increase is similar to
the increase in stoke volume and systolic pressure of approximately 3-7% in SPV [1-
3,17]. Therefore, we can see that the ∆up of SPV or the transient increase in stroke
volume is caused by the increase in intrathoracic pressure of positive pressure breathing.
21
CHAPTER 6
∆DOWN
In order to understand the ∆down portion of SPV, the steady state response of the
circulation must be explored. This response is observed after the transient augmentation
of stroke volume. Guyton and associates describe a model of the circulation that
provides a graphical analysis of the steady state response of the circulation to
physiological changes [20-26].
Guyton’s Graphical Model
Guyton’s representation of the circulation is based on two curves, the Cardiac
Function Curve and the Vascular Function Curve, both shown below [20-22].
Figure 18. Cardiac and Vascular Function Curves. Guyton AC: Graphical analysis of
cardiac output regulation. In: Circulatory Physiology: Cardiac Output and Its
Regulation. Saunders: Philadelphia, Pennsylvania, 238, 1973.
22
These curves represent the function of the heart and the vasculature of the body
that Guyton and associates established through varied experiments [20,22]. The
experiments involved isolating the heart from the vasculature and testing their cardiac
output, venous return, and respective atrial pressures independent of each other [20]. An
example of their experiments is shown below.
Figure 19. Guyton’s Experiments. Guyton AC: Effect of right atrial pressure on venous
return – the normal venous return curve. In: Circulatory Physiology: Cardiac Output
and Its Regulation. Saunders: Philadelphia, Pennsylvania, 189, 1973.
The Cardiac Function Curve represents the ability of the heart to deliver a specific
cardiac output to the body at a particular atrial pressure [21].
23
Figure 20. Cardiac Function Curve. Modified from Guyton AC: Graphical analysis of
cardiac output regulation. In: Circulatory Physiology: Cardiac Output and Its
Regulation. Saunders: Philadelphia, Pennsylvania, 238, 1973.
The Vascular Function Curve represents the ability of the vasculature to deliver a
specific venous return to the heart at a particular atrial pressure [22].
24
Figure 21. Vascular Function Curve. Modified from Guyton AC: Graphical analysis of
cardiac output regulation. In: Circulatory Physiology: Cardiac Output and Its
Regulation. Saunders: Philadelphia, Pennsylvania, 238, 1973.
Just as the venous return and cardiac output must equal each other in steady state,
the steady state response of the circulation to the body’s physiological state is determined
by the intersection of these two curves [25]. At the intersection of these two curves, we
can see the atrial pressure and the cardiac output or the venous return [25]. An example
is shown below.
25
Figure 22. Intersection of the Cardiac and Vascular Function Curves. Guyton AC:
Graphical analysis of cardiac output regulation. In: Circulatory Physiology: Cardiac
Output and Its Regulation. Saunders: Philadelphia, Pennsylvania, 238, 1973.
These curves change in predictable ways in response to physiological changes
[21-26] Physiological effects that were determined through experimentation by Guyton
and associates include sympathetic stimulation, cardiac hypertrophy, decreased load on
the heart, myocardial infarction, parasympathetic stimulation, decreased vascular
resistance, changes in vascular capacitance, blood loss, transfusion, positive pressure
breathing, negative pressure breathing, opening of the chest, muscular compression of the
vascular system, and vasomotor tone [21-26]. In response to higher sympathetic
stimulation, the Cardiac Function Curve is augmented due to the increased contractility
of the heart [21]. Shown below is the augmentation of the Cardiac Function Curve by
sympathetic stimulation.
26
Figure 23. Effects of sympathetic stimulation on the Cardiac Function Curve. Guyton
AC: Patterns of cardiac output curves. In: Circulatory Physiology: Cardiac Output and
Its Regulation. Saunders: Philadelphia, Pennsylvania, 163, 1973.
The effect of an instantaneous change in blood volume is to shift the Vascular
Function Curve right or left and increase or decrease the slope. The Vascular Function
Curve shifts to the right and increases slope for transfusion and shifts to the left and
decreases slope for blood loss [23,26]. The reason that the curve shifts is that mean
circulatory pressure changes with blood volume changes [23]. Guyton tells us that the
slope changes because with greater volume the vasculature distends and the resistance to
flow decreases [23,26]. Below is a graph showing the effects of instantaneous changes in
blood volume.
27
Figure 24. Effects of instantaneous blood volume changes on the Vascular Function
Curve. Guyton AC: Effect of blood volume changes and orthostatic factors on cardiac
output. In: Circulatory Physiology: Cardiac Output and Its Regulation. Saunders:
Philadelphia, Pennsylvania, 357, 1973.
Another physiological change that we will discuss is the effects of positive
pressure breathing [21,27]. Positive pressure causes mostly a shift in the Cardiac
Function Curve to the right and a slight decrease in slope of the Venous Return Curve
due to a slight increase in resistance in the vasculature [21,27]. The results of the
experiments done with positive pressure are shown below.
28
Figure 25. Effects of positive pressure on the Cardiac and Vascular Function Curve.
Fermoso JD, Richardson TQ, Guyton AC: Mechanism of decrease in cardiac output
caused by opening of the chest. Am J Physiol. 207(5): 1115, 1964.
SPV is Caused by Positive Pressure Breaths
The positive pressure used in the experiments above was equivalent to
approximately 4-mmHg [27]. According to Gilbert and Glantz, the contact pressure
associated with positive pressure ventilation with a typical tidal volume of 15-20 ml/kg is
less than 2-mmHg [28]. Thus, the effects of positive pressure in positive pressure
ventilation are less than half of those shown on the graph above. So, using extrapolation
of halfway in between the two curves, the following curves were acquired.
29
Figure 26. Approximate effects of positive pressure of positive pressure ventilation on
function curves.
There is an approximate decrease of 160 cc/min in cardiac output or stroke
volume from point A to point C. This is a decrease of about 9.4%. This would
correspond to an approximate 9.4% decrease in systolic pressure in SPV. The actual
decrease in systolic pressure of SPV at normal blood volume is approximately 5-12%
depending on the tidal volume used, which matches fairly closely [1-3].
30
CHAPTER 7
SPV INCREASES WITH BLOOD LOSS
Guyton and associates also conducted experiments with changes in blood volume
[26]. The effects of transfusion on the function curves are shown below.
Figure 27. Effects of transfusion on function curves. Guyton AC: Effect of blood volume
changes and orthostatic factors on cardiac output. In: Circulatory Physiology: Cardiac
Output and Its Regulation. Saunders: Philadelphia, Pennsylvania, 363, 1973.
The first effect is that the Vascular Function Curve shifts to the right and
increases slope because of the increased blood volume, shown at point B [26]. Then, the
compensatory effects of the body to the increased blood volume cause further changes to
the curves [26]. One of these changes is a reflex relaxation of the vasculature and the
heart [26]. This relaxation shifts the Vascular Function Curve to the left and decreases
in slope while the Cardiac Function Curve shifts down and to the right, shown at point C
31
[26]. After ten minutes, the curves further change because of stress relaxation, shown at
point D [26]. In response to stress relaxation, the Vascular Function Curve shifts further
to the left and further decreases in slope [26]. The Cardiac Function Curve recovers a bit
and shifts back up and to the left [26].
The Effect of Blood Loss and Compensation Mechanisms on the Function Curves
The effects of blood loss on the function curves are nearly opposite that of
transfusion. First, the Vascular Function Curve shifts to the left and decreases in slope
due to the decrease in blood volume [23,26]. This is due to the reduction in mean
circulatory pressure and the increase in vascular resistance [23-24,26]. The
compensation mechanisms of the body for blood loss include sympathetic stimulation,
nervous reflexes, and slower compensations of stress relaxation recovery, and
readjustment of blood volume [26]. The effect of the sympathetic stimulation is to
increase the contractility of the heart and augment the Cardiac Function Curve. The
nervous reflex of the vasculature is to constrict. This causes an increase in mean
circulatory pressure and a shift to the right of the Vascular Function Curve. The stress
relaxation recovery has the effect of the vasculature recovering its elasticity, mostly in the
veins, and more tightly clamping down on the reduced blood volume of the body [26].
This also has the effect of returning the Vascular Function Curve more towards normal
[26]. The readjustment of blood volume involves the movement of fluid from the tissues
to the plasma because of the greater osmalarity of the plasma after blood loss [26,29-31].
Guyton also explains that this effect serves to return the Vascular Function Curve
towards normal [26]. The overall change in the function curves after 10% blood loss was
32
determined from graphical analysis of the curves provided by Guyton and associates.
This overall change is shown at point D in the figure below.
Figure 28. Graphical analysis of the effects of 10% blood loss on the function curves.
Will ∆down Increase with Blood Loss According to Guyton’s Model?
In order for ∆down to increase with blood loss, the change in stroke volume due
to positive pressure after blood loss must be greater than the change in stroke volume due
to positive pressure at normal blood volume. Because the positive pressure shifts the
Cardiac Function Curve the same amount at both blood volume states, a greater change
would require an increase in the slopes of the functional curves after blood loss.
However, in the model shown above, there is an overall decrease in slope between the
two curves, even though the Cardiac Function Curve does increase in slope slightly.
Furthermore, to compare ∆down after 10% blood loss to normal blood volume, a
33
graphical analysis of the effects of positive pressure ventilation on the 10% blood loss
was done similar to the one for normal blood volume. Below is an approximation of the
effects of positive pressure on the function curves after 10% blood loss. The point D1
represents the cardiac output with positive intrathoracic pressure.
Figure 29. Graphical analysis of the effects of positive pressure on the functional curves
after 10% blood loss.
The decrease in stroke volume in this case is 140 cc/min. This decrease of 140
cc/min is actually less than the decrease in stroke volume of 160 cc/min at normal blood
volume. These decreases in stroke volume are approximately proportional to ∆down for
each case respectively. Therefore, after 10% blood loss, ∆down would have actually
decreased by approximately 10%. This is exactly opposite the result we expected.
Below is shown a comparison of the decrease in stroke volume for normal blood volume
and the decrease in stroke volume after 10 % blood loss. As can be seen through careful
34
measuring, the decrease in stroke volume from A to A1 is greater than the decrease from
D to D1.
Figure 30. Comparison of the effects of positive pressure ventilation on the normal
function curves and the function curves after 10% blood loss.
What Went Wrong?
Guyton admits that our understanding of the compensation mechanisms to blood
loss is only partially understood [26]. In later publications, Holcroft and Jacobsohn
provide a greater understanding of the compensation mechanisms for blood loss [30-31].
They both discuss how compensation mechanisms of sympathetic stimulation,
vasoconstriction, stress relaxation, and readjustment of blood volume all serve to
augment cardiac output and venous return for acute blood loss [30-31]. However, they
note that these mechanisms fail to augment cardiac output after severe blood loss [30-31].
In addition, they both mention that after some time the movement of the fluid from the
35
tissues and interstitial spaces to the plasma serves to dilute the blood and make the blood
less viscous [30-31]. Holcroft states that this reduces the afterload on the heart and
further augments the Cardiac Function Curve [30]. Jacobsohn goes even further to say
that this dilution of the blood serves to reduce the resistance of the blood to flow and
increases the slope of the Vascular Function Curve [31]. If the Vascular Function Curve
did actually increase in slope for acute blood loss, then the slopes for both functional
curves would increase. If both function curves increase in slope, then positive pressure
ventilation would cause a greater decrease in stroke volume after blood loss than at
normal blood volume. This would cause ∆down to increase with blood loss as was
observed by Perel and many others.
Unfortunately, no data exists which show the Vascular Function Curve with an
increase in slope after blood loss. But, there are studies that suggest that the vascular
resistance decreases and therefore the slope should increase [29-31]. Jacobsohn provides
a graph with his publication that shows the effects of blood loss on the function curves,
which is shown below.
36
Figure 31. Functional curves provided by Jacobsohn. Jacobsohn E, Chorn R, O’Conner
M: The role of the vasculature in the regulating venous return and cardiac output:
historical and graphical approach. Can J Anaesth. 22(8): 859, 1997.
However, he does not state the amount of blood loss that he is assuming and does
not infer that the body has had enough time for the slow effect of blood readjustment to
take place. Nevertheless, if we use his graph and apply the same graphical analysis for
positive pressure ventilation that we performed previously on Guyton’s graphs, we find
that stroke volume or cardiac output is indeed decreased more after blood loss. This
means that ∆down increases with blood loss as was observed by Perel and others.
37
Figure 32. Graphical analysis of the effects of positive pressure on the normal function
curves and the function curves after blood loss.
As can be seen through careful measuring, delta2 is greater than delta1. The
stroke volume actually decreased approximately 45% more after blood loss than at
normal blood volume. This greater decrease in stroke volume accounts for the greater
∆down and greater SPV after blood loss than at normal blood volume.
38
CHAPTER 8
ADDITIONAL STUDIES OF PHOTO-PLETHYSMOGRAPHIC PULSE WAVEFORM
VARIATIONS
In our lab we performed our own experiments which attempted to quantify the
effects of blood loss on photo-plethysmographic pulse waveform variations. Our study
attempted to establish a continuous monitor of blood volume status by only monitoring
the total PWV and not establishing a baseline plateau of peak plethysmographic pulse
signal at apnea. The protocol of our study was simply to continuously record the best
available PWV on a tongue, foot or ear of the animal. Then, the animal was bled of 75%
of their estimated blood volume.
Results
The results of our study turned out to be somewhat different than what was
expected. We expected that the PWV would increase with blood loss at least until about
30% of the estimated blood volume was shed. However, in a study of four animals, the
PWV held constant or increased for a time then dramatically decreased. An example of
this dramatic decrease in PWV is shown below.
39
Before Blood Loss After Blood Loss
Figure 33. Example of dramatic decrease in PWV after blood loss.
This dramatic decrease happened at various estimated blood losses, sometimes
before even 10% blood loss. The magnitude of PWV and %PWV at various estimated
blood losses are shown below for all four animals.
POWV 28-Jun 16-Sep 23-Sep 6-Oct Normal 5416.667 1111 1461.333 108
10% 3969.667 1071 1461.333 139.5333 25% 2727.5 838.3333 1132.667 144.0667 50% 2336.667 621 452.3333 94.53333 75% 726.6667 550.5 409.5 41.01333
Table 2. The magnitude of PWV at various blood volumes.
40
PWV 28-Jun
01000
20003000
40005000
6000
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
Mag
nit
ud
e o
f P
WV
PWV 16-Sep
0200400600800
10001200
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
Mag
nit
ud
e o
f P
WV
PWV 23-Sep
0
200
400
600
800
1000
1200
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
Mag
nit
ud
e o
f P
WV
PWV 6-Oct
0
50
100
150
200
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
Mag
nit
ud
e o
f P
WV
Figure 34. The magnitude of PWV at various blood volumes.
%POWV 28-Jun 16-Sep 23-Sep 6-Oct Normal 0.023807 0.02221 0.044942 0.003553
10% 0.017056 0.020549 0.045624 0.00443 25% 0.011883 0.015753 0.036431 0.004352 50% 0.009376 0.010462 0.013493 0.002615 75% 0.00651 0.00778 0.013829 0.001079
Table 3. The %PWV at various blood volumes.
41
%PWV 28-Jun
00.0050.01
0.0150.02
0.025
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
%P
WV
%PWV 16-Sep
0
0.0050.01
0.0150.02
0.025
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
%P
WV
%PWV 23-Sep
0
0.010.020.030.04
0.05
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)
%P
WV
%PWV 6-Oct
0
0.0010.002
0.0030.004
0.005
0 20 40 60 80
Estimated Blood Loss (% Blood Volume)%
PW
V
Figure 35. The %PWV at various blood volumes.
In the first animal, the PWV decreased immediately. In the second animal, the
PWV held constant until 10% blood loss. In the third animal, the %PWV increased until
10% blood loss. And finally, in the last animal, PWV increased until 25% blood loss.
Discussion
As discussed above, Holcroft and Jacobsohn state that some major compensation
mechanisms are only effective in augmenting the Cardiac Function Curve and the
Vascular Function Curve for acute and moderate blood loss [30-31]. In a more severe
state of hypovolemic shock, these mechanisms are no longer effective and the slopes of
the function curves will decrease [30-31]. This will cause PWV to decrease also.
However, we did not expect these effects to happen so soon after initiating bleeding as
happened in our study.
42
Holcroft and Jacobsohn both mention that these compensation mechanisms also
have a slow response time [30-31]. In some animals of our study, these compensation
mechanisms were not allowed to take effect because we bled the animals too quickly.
The second animal in particular was bled 75% of the estimated blood volume in only 5
minutes. The third and fourth animals were bled a little slower at 8 and 9 minutes,
respectively. In contrast, Perel waited 15 minutes after each blood loss before measuring
SPV in his studies [1]. This explains why in the second animal PWV never increases and
dramatically decreases after only 25% blood loss.
Another of the biggest problems that we had in our study was that we could not
get a consistent signal strength on the photo-plethysmographic signal. This caused
problems in that the magnitude of PWV varied with the signal strength, which would
change when bumping, moving, or otherwise changing the position of the animal. In
addition, another compensation mechanism of the body not mentioned above is that
during blood loss, we can expect the body to react to hypovolemic shock by shutting
down blood perfusion to the periphery or our site of monitoring PWV. This would cause
the signal strength of the photo-plethysmographic signal to decrease and thus decrease
the measured PWV. This undoubtedly caused the PWV to decrease sooner than
expected. Furthermore, the signal strength on a fifth animal was so weak that the pulse
could never be determined through the signal and the results were not used in this study.
Interestingly, the catheter of the first animal was changed shortly after the initiation of
bleeding. This dramatically changed the position of the animal and caused the signal
strength to greatly decrease. This may have been responsible for the immediate decrease
in PWV in the first animal.
43
In summary, the PWV or %PWV increased in two animals until 25% or 10%
blood loss respectively. In the other two animals, the PWV decreased almost
immediately due to either bleeding the animal too fast or decreasing the signal strength
by dramatically changing the position of the animal. In the animal that PWV did
increase, the increase in PWV at 10% blood loss was approximately 28.8%.
In addition, a graphical analysis was done for the effects of a positive pressure
breath after a 75% blood loss without the compensation effects present after acute blood
loss. The graph below shows how the function curves change after 75% blood loss
without the effects of compensation mechanisms.
Figure 36. The change in the function curves after 75% blood loss without compensation
mechanisms.
44
The graphical analysis of the effects of positive pressure ventilation on the
function curves of 75% blood loss without compensation mechanisms is also shown
below.
Figure 37. Graphical analysis of the effects of positive pressure on the function curves
after 75% blood loss but with no compensation mechanisms.
The point B1 represents the decrease in stroke volume with positive pressure.
This analysis showed that in comparison to normal blood volume, the stroke volume
decreased approximately 62% less after 75% blood loss. Thus, PWV should also
decrease by approximately 62%. This is similar to the average 67% decrease in PWV
after 75% blood loss found in our studies.
In the end, our lab abandoned the pursuit of a continuous monitor of blood
volume through PWV because of the inconsistencies in the signal strength of photo-
plethysmographic signal.
45
CHAPTER 9
FURTHER WORK
In order to better understand SPV and other similar noninvasive indicators of
monitoring blood volume, we must better understand the compensation mechanisms that
effect these indicators. To better understand these compensation mechanisms, we must
understand how they affect the function curves and the response times of the curves to
these compensation mechanisms.
An effective way to obtain this understanding of these mechanisms would be to
perform a new set of experiments on animal models. First of all, in an animal model, the
Cardiac Function Curve and the Vascular Function Curve would be established using the
experimental methods used by Guyton and associates [20-22]. Also, the SPV and PWV
would be recorded using Perel’s method [1,17]. Then, we would bleed the animal of a
10% of their blood volume and allow time for the compensation mechanisms to take
effect. Next, the SPV and PWV would be measured using Perel’s methods to confirm an
increase in SPV and PWV. Finally, the Cardiac Function Curve and the Vascular
Function Curve would be determined again through Guyton’s methods to determine the
change in the curves that caused SPV and PWV to increase. This process could be
repeated again for 25% blood loss and greater blood loss to establish when these
mechanisms were no longer effective and no longer caused SPV and PWV to increase.
In addition, the function curves could be determined at different times after each blood
loss to determine how long before these mechanisms were effective in increasing SPV
and PWV.
46
In this way, our understanding of blood loss, compensation mechanisms, and
indicators of blood volume status would be greatly enhanced. This understanding would
help us better diagnose blood loss noninvasively and help us to better treat it effectively.
47
CHAPTER 10
CONCLUSION
Positive Pressure Ventilation causes a transient increase in systolic pressure
termed ∆up and a subsequent decrease in systolic pressure termed ∆down. The increase
in systolic pressure can be explained by a temporary augmentation of stroke volume.
This augmentation is caused by the effects of increased intrathoracic pressure better
understood through a graphical analysis similar to those done by Bromberger-Barnea on
decreased intrathoracic pressure. The decrease in systolic pressure can be explained by
graphical analysis using the model of the circulation established by Guyton and
associates. This model shows that the steady state response of the circulation to positive
intrathoracic pressure is a decrease in stroke volume and thus a similar decrease in
systolic pressure.
However, the current models of circulation do not adequately explain the greater
decrease in stroke volume and the increase in SPV with blood loss. Guyton’s model
actually predicts a decrease in SPV with blood loss. Later revisions of this model imply
that an increase in SPV with blood loss is possible through compensation mechanisms
that increase the slope of both the Cardiac Function Curve and the Vascular Function
Curve. However, the increase in these slopes have never been quantified, therefore a
concrete conclusion as to the cause of the increase in SPV is not currently available.
In addition, a similar noninvasive monitor of blood volume, PWV, was found to
often decrease with blood loss. This increase was caused by not allowing compensation
48
mechanisms to have an effect on PWV or through a decrease in signal strength due to
either moving the animal or the shut down of peripheral blood perfusion.
These compensation mechanisms could be greater understood through further
studies into the function curves after varying degrees of blood loss. These studies could
assist in more effectively diagnosing and treating blood loss.
49
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