Cerebral Blood Flow and Metabolism
Studies Comparing Krypton 85
Desaturation Technique With
Argon Desaturation Technique
Using the Mass Spectrometer
BY MARK L. DYKEN, M.D.
Abstract:
Cerebral
Blood Flow
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and Metabolism
Studies
Comparing
Krypton 85
Desaturation
Technique
With Argon
Desaturation
Technique
Using the
Mass
Spectrometer
• Average cerebral blood flow determinations were performed 26 times
comparing argon desaturation curves measured by mass spectrometry to the
krypton 85 desaturation technique of McHenry.1 During 17 of these studies
krypton 85 and argon desaturations were performed simultaneously. Mean
cerebral blood flow difference was 7.2 ± 5.7% for simultaneous determinations
and 7.9 ± 6.6% for the total, establishing that the two techniques are
comparable. Some of the advantages of using argon in mass spectrometry
include: no blood needs to be withdrawn, curves can be observed at the time
they are obtained, radiation precautions are not required, multiple studies do
not affect the patient, and partial pressures of oxygen and carbon dioxide can be
observed constantly.
Additional Key Words
percutaneous cannulation
blood gas monitoring
• Despite the many new methods to measure
regional and total cerebral blood flow (CBF),
the method for determining average blood flow
originally introduced by Kety and Schmidtusing the Fick principle remains the most
reliable. Because it is relatively simple technically and can easily measure cerebral
metabolic rate (CMROo), it has not been
replaced by newer techniques. Utilizing the
principles of the original nitrous oxide saturation studies, a number of variations in
procedure and in inert gases have evolved. One
of the best of these is the krypton 85
desaturation method of McHenry. 1 From
From the Department of Neurology, Indiana University School of Medicine, 1100 West Michigan Street,
Indianapolis, Indiana, 46202.
This investigation was supported by Cerebral
Vascular Disease Research Center Grant PHS NS
06793.
Stroke, Vol. 3, May-June 1972
cerebral vascular disease
jugular bulb
Pco.»
Poo
experience gained from a total of 325 cerebral
blood flow measurements using this method we
conclude that in our hands it is much more
reliable and repeatable than our previous
measurements obtained from the nitrous oxide
saturation technique. In our laboratory, reproducibility of CBF measurements using krypton
85 is 5.8 ± 3.8%. 3 Despite this, problems exist
in performing these studies. These include:
1. Six to ten persons are required during the
procedure.
2. For each desaturation study a minimum
of 86 to 100 ml of blood must be
removed. Four different measurements
require close to 400 ml of blood.
3. Rare technical difficulties with stopcocks,
frozen syringes, etc., may require a
procedure to be repeated.
4. Extensive equipment and laboratory
preparation require a minimum of two
hours before the procedure and four
279
DYKEN
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hours after for clean-up and analysis. A
minimum of 24 minutes is spent for
each actual cerebral blood flow determination.
5. Extensive radiation precautions are required by the Atomic Energy Commission.
6. Final results are not available after the
procedure but are delayed until blood
analysis and calculations are completed.
7. Technical, needle and gas delivery difficulties are not recognized until calculations are completed. Therefore, if a
procedure needs to be repeated the
patient must be brought back to the
procedure room and arterial and
venous punctures repeated.
8. There is no way of checking changes in
oxygen and carbon dioxide in the blood
until analyses are completed.
Recently intravascular catheters have
been developed that have special gas permeability characteristics and can remain intravascularly for at least 24 hours without generating
thrombi. 4 ' 5 With these catheters, continuous
measurement of blood gases in vivo by mass
spectrography can be made. Woldring et al.6
established this technique in animals in 1966
and Hass et al.7 in humans in 1968. They
demonstrated that cerebral blood flow can be
measured using inert gases with this technique.
To solve the problems with the krypton 85
method, a clinical mass spectrometer (Medspect MS-8, developed and manufactured by
Scientific Research Instruments Corp., Baltimore, Maryland) was acquired. In addition to
being able to repeatedly measure cerebral
blood flow without affecting the patient, partial
pressures of oxygen and carbon dioxide can be
continuously monitored in seriously ill patients.
The instrument measures oxygen, carbon
dioxide, nitrogen, and argon from one of two
catheters which can be automatically switched
at 40-second intervals. Pevsner et al.8 studied
eight normal patients with this technique using
argon and obtained results similar to those
reported using other techniques. The purpose
of this paper is to compare the results obtained
from argon desaturation curves measured by
the mass spectrometer to those from the
krypton 85 desaturation technique of McHenry-1
TRANSIENT ISCHEMIC ATTACKS-LEFT INTERNAL CAROTID ARTERY ( «0 YEAR OLD MALE BREATHING 190XOXYGEN)
n,ooo-
FIGURE 1
Simultaneous argon and krypton 85 desaturation curves for calculation of average cerebral
blood flow.
280
Sfrok*. Vol. 3, May-June 1972
CBF AND METABOLISM STUDIES
Methods
Two gas-sterilized 18-inch long 22-gauge stainless
steel tubing catheters sheathed in heparinized
silastic are connected to four-foot or six-foot
stainless steel cannulas sheathed in Teflon connected to the mass spectrometer. Sterile technique
is maintained. The mass spectrometer is set for
blood mode and placed on "operate," and the
catheters are allowed to equilibrate with air while
the vascular punctures are performed. The
spectrometer has been previously balanced for
oxygen, carbon dioxide, argon, and nitrogen in a
constant temperature water bath with a calibration gas mixture. After at least 10 to 15 minutes
of pumping time the oxygen read-out is balanced
for each catheter. The calculations are made from
a calibration chart based on barometric pressure
and room temperature.
One of the brachial arteries (in one case the
right femoral artery) is cannulated by a special 8inch long 17-gauge angiography needle with a 15gauge Teflon catheter sleeve. This needle was
specially designed and made by Beckman-Dickinson Company for Dr. William Hass and his group
MEAN ARTERIAL PRESSURE (mm Hg)
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200 T
150 •100-50--
n n
T OXYGEN pO2
CARBON DIOXIDE pCO2
80
60-40-20--
o-L
VENOUS PRESSURE (mm Hg)
EKG
500 T NITROGEN
400 -300 -200 • 100 •-
0-L ARGON
27
0
1
Off Oo
r
2
3
4
5
6
7
M I N U T E S
8
9
10
11
12
FIGURE 2
Polygraph recording obtained during argon and krypton 85 desaturation while breathing 100%
oxygen. Taken from the same patient at the same time as figure 1.
Stroke, Vol. 3, May-June 1972
281
DYKEN
TABLE 1
Comparison of Results Obtained by Krypton 85 and Argon Desaturation Techniques
C*r«W«4 Mood flaw
(w/1 M Qm/mtn)
K/AX
Simultaneous
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No.
pt.
KrU
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
1
1
2
2
2
3
3
3
4
4
5
5
5
6
6
6
Air
17
3
4
5
7
8
9
8
1
2
Ar
K-A
+1
47
44
58
43
28
44
50
45
59
53
66
45
45
60
55
46
57
46
51
59
44
24
42
50
50
56
64
62
42
46
58
57
51
66
17
17
50
9.0
17
51
10.2
Air
Air
Air
Air
Air
Air
50
53
45
39
51
39
39
47
43
45
55
42
41
40
40
39
42
35
+ 11
26
48
8.1
26
26
48
o,
co,
Air
o2
CO2
Air
o,
CO2
Air
o2
Air
o2
CO2
Air
o2
CO,
-7
-1
-1
+4
+2
0
-5
+3
-11
+4
+3
-1
+2
-2
-5
-9
%
2.2
14.7
1.7
2.3
15.4
4.7
0
10.4
5.2
18.6
6.3
6.8
2.2
3.4
3.4
10.2
14.5
111
102
86
98
98
117
105
100
90
105
83
106
107
98
103
96
90
86
Subtotal
N
Mean
S
Nonsimultaneous
18
19
20
21
22
23
24
25
26
o2
Air
Air
17
3.6
3.0
+5
-2
+3
-2
-1
0
+5
+8
17
7.2
5.7
17
98
9.0
10.4
3.7
6.8
5.0
24.2
2.5
0
11.2
20.5
111
96
107
95
128
98
100
112
123
26
7.9
6.6
26
102
10.9
Total
N
Mean
S
at New York University Medical Center. After the
artery is punctured, the needle is removed and the
catheter sleeve inserted four to six inches into the
artery. The mass spectrometer silastic catheter is
inserted through a sterile Tuohy-Borst Female
Luer-lok tip which has an additional angled
female Luer-lok side connection and then into the
intra-arterial catheter so the silastic-covered
porous tip extends above the tip of the Teflon
catheter and lies directly in the blood stream. The
connections are tightened and the side connection
is connected to a bank of syringes by a three-way
stopcock so blood can be withdrawn for measurement of krypton 85 desaturation and for volumes
282
9.8
3.8
3.2
percent of oxygen or is connected to a pressure
transducer for arterial pressure recording.
A similar needle and sleeve is inserted just
lateral to the common carotid artery at midneck.
In most instances the internal jugular vein was
located with a Parks Doppler directional ultrasound flowmeter and the side of insertion
determined by maximal venous frequency. The
needle is inserted to resistance or until the tip is
estimated to be deep to the artery. The needle is
then removed and gentle aspiration is performed
on the catheter with an attached syringe. If no
venous blood returns, the catheter is slowly
withdrawn while continuous negative pressure is
Stroke, Vol. 3, Moy-June 1972
CBF AND METABOLISM STUDIES
CtrvfcraJ o i y i i n loniumptton
(ccol/iMgm/mln)
C*r«bral vauslar rcttetaiK*
H|/n/lH|»/«•In)
K/AX
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Kr 13
AT
K-A
37
2.6
3.1
3.4
2.0
2.4
3.7
3.3
3.0
3.2
2.7
2.9
2.5
3.4
27
2.3
2.0
3.6
3.1
3.2
3.5
1.7
2.3
37
3.6
2.9
3.9
2.5
2.8
2.5
3.2
2.8
2.5
2.3
+ 0.1
17
2.9
0.54
17
2.9
0.60
3.7
3.2
2.9
2.5
3.1
3.0
3.4
3.1
2.6
2.8
2.3
37
3.4
2.6
2.9
3.0
25
2.9
0.53
25
2.9
0.51
-0.5
-0.1
-0.1
+ 0.3
+ 0.1
0
-0.3
+ 0.1
-0.7
+ 0.2
+ 0.1
0
+ 0.2
-0.1
-0.2
-0.3
17
0.20
0.18
+ 0.7
-0.2
-0.2
-0.1
+ 0.3
-0.3
+ 0.8
+ 0.4
25
0.26
0.22
111
Kr»
Ar
103
84
97
97
118
104
100
92
103
82
108
104
100
106
96
92
87
3.5
3.7
2.8
3.1
5.3
4.3
2.4
2.6
2.3
2.3
2.0
2.8
3.1
2.5
17
2.0
1.7
3.5
3.2
2.8
3.0
6.1
4.5
2.4
2.4
2.4
1.9
2.1
3.0
3.0
2.6
1.6
1.8
1.5
17
7.1
6.1
17
98
9.2
17
2.8
0.95
17
2.8
1.13
17
K-A
0
+ 0.5
0
+ 0.1
-0.8
-0.2
0
+ 0.2
-0.1
+ 0.4
-0.1
-0.2
+ 0.1
-0.1
+ 0.1
+ 0.2
+ 0.2
0.19
0.20
%
0
14.5
0
3.2
14.0
4.6
0
8.0
4.2
19.0
4.8
6.9
3.2
3.8
12.1
10.5
12.5
17
7.1
57
111
100
116
100
103
87
96
100
108
96
121
95
93
103
96
106
111
113
17
103
9.0
20.6
6.1
67
3.9
10.2
123
94
94
96
111
2.4
2.3
2.8
2.8
1.8
2.6
2.3
3.2
27
2.3
-0.2
0
-0.4
-0.5
8.0
0
13.3
3.6
24.4
12.2
24.2
12.5
88
128
113
2.3
3.5
3.1
2.4
3.9
4.4
-0.1
—0.4
-1.3
4.3
10.8
34.7
96
90
70
25
8.7
25
101
25
2.8
0.83
25
2.9
1.02
25
8.8
25
99
11.3
6.7
11.6
exerted. When venous blood is easily obtained, a
15-inch stainless steel wire guide with Teflon coat
and fixed core with a flexible tip is inserted toward
the jugular bulb. When it passes easily, the Teflon
sleeve is then passed up over the guide wire until
resistance is met or until by measurement the
jugular bulb should be approached. In most cases
when the catheter reaches the bulb, resistance is
met and the patient complains of subjective pain
in the ear. During the first procedures the wire
guide was left in place and radiograms revealed
proper placement in 100% of the cases. Because
of this radiograms were not performed in later
cases. Once the catheter is in place the guide wire
SfroW, Vol. 3, Moy-June 1972
K/AX
%
27
17.5
3.2
2.9
16.2
4.2
0
8.6
3.3
19.4
7.7
3.4
0
6.1
3.6
8.3
14.0
+ 0.1
25
0.25
0.29
8.3
92
100
88
104
78
is removed and the mass spectrometer catheter is
inserted until slight resistance is met indicating the
tip is in the jugular bulb. At this point the Teflon
catheter sleeve is pulled back so the porous tip lies
freely in the blood stream in the jugular bulb. The
same connections are made to the recording
instrument as was done for the arterial pressure.
Since this study was completed it has become
apparent that ideally the catheters should be
calibrated in vivo. Constant recordings were made
on a Grass Model 7 Polygraph from the mass
spectrometer for carbon dioxide, oxygen, nitrogen, and argon content and directly for arterial
283
DYKEN
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and venous blood pressures and electrocardiography. A slave Recti-riter recorder was connected
to the Grass Model 7 DAC power amplifier to
obtain higher amplitude and larger curves for
argon gas measurement. After all parameters had
been determined to be constant and a good
baseline had been obtained for the simultaneous
studies, the patient was allowed to breathe a
mixture of 1 me of krypton 85 per liter of air of
which 9.2% of the nitrogen had been replaced by
argon. A nine-liter respirometer with an oxygen
regulator, flowmeter, and carbon dioxide absorption unit was used. Saturation occurred for a
minimum of 12 minutes or until argon was
observed to reach equilibrium in the arterial and
venous blood as observed on direct read-out from
the mass spectrometer. In addition, the oxygen
and nitrogen determinations were observed closely
as in some cases the flow over the venous catheter
would be too slow to obtain adequate recordings.
In these instances both oxygen and nitrogen
would drop, and argon would not reach equilibrium. In the patients in whom this occurred the
head and the catheter tip were repositioned and
the head tilted from side to side until the deficit
was corrected. In all cases studied to date, after
manipulation flow became adequate for mass
spectrometer determinations. Once the argon had
reached equilibrium, the patient was switched
from the saturation mixture to either room air,
5% carbon dioxide, or 100% oxygen for
desaturation studies. During desaturation constant
recording was performed on the mass spectrometer simultaneously while blood was withdrawn at
intervals as described by McHenry1 for the
krypton 85 desaturation curve. In addition
approximately 10 cc of arterial and venous blood
was drawn at four minutes and five seconds to
CMRC =
four minutes and 20 seconds into desaturation for
analysis for Po.,, Pco.» PH ar>d volumes percent
oxygen for comparison to the mass spectrometer
and to obtain the oxygen volumes percent for
cerebral oxygen consumption determinations.
During nonsimultaneous studies the same technique was performed for the krypton 85 desaturation curves except argon was not in the mixture.
For the separate argon desaturation curves the
patient was saturated directly from a tank of air in
which 9.2% nitrogen had been replaced with
argon.
Calculations
Following the completion of the studies blood was
analyzed for krypton 85 and calculations of
284
cerebral blood flow were determined as described
by McHenry.1
Before the calculations for argon were made
from the mass spectrometer recordings, the
catheters were calibrated again in a constant
temperature (37°C) water bath with a calibration
gas mixture. If variations between the catheters
were observed, correction factors were determined. Following this the areas under the venous
and arterial argon desaturation curves were
measured a minimum of two times with a
standard planimeter. The cerebral blood flow was
calculated from the following formula:
CBF =
(VCS-VCD)IOO
(AVC - AAC X cf#l)cf#2
VCS is the height in inches of the venous curve at
saturation and VCD is the height at desaturation.
AVC is the area under the venous desaturation
curve in square inches and AAC is the area under
the arterial curve. cf#l is a correction factor
determined from variations in catheter recording
of argon from the calibration mixture in the
constant temperature bath and is determined by
dividing the argon read-out for the venous
catheter by the read-out for the arterial catheter.
cf#2 is the reciprocal of the speed of the recorder
in inches per minute (see fig. 1). VCS and VCD
are determined by direct measurement and AVC
and AAC are determined by the planimeter. The
calibration bath recorded 62 for venous catheter
for argon and 60 for the arterial. Therefore, cf#l
equals 1.03. As the Recti-riter recorder moved 1.5
inches per minute, cf#2 was determined by 1/1.5
or 0.6667. Cerebral vascular resistance (CVR)
and cerebral metabolic rate (CMRO.,) are
calculated in the usual manner.
A-V vol % oxygen
100
X CBF.
Results
Nine patients with transient ischemic attacks or
ischemic infarction were studied 26 times by
each technique. During 17 of these studies
krypton 85 and argon desaturation were
performed simultaneously. During each study
permanent recordings were made on the Grass
recorder of mean arterial blood pressure, mean
venous blood pressure, carbon dioxide, oxygen,
nitrogen and argon (fig. 2 ) . Argon curves were
slaved to a Recti-riter recorder for actual
determination of area under the curve (fig. 1)
and krypton 85 desaturation curves were recorded (fig. 1). Table 1 demonstrates the degree of correlation. The mean cerebral blood
Stroke, Vol. 3. May.Juntt 1972
CBF AND METABOLISM STUDIES
flow difference was 7.2 ± 5.7% for simultaneous determinations and 7.9 ± 6.6% for all
26. The cerebral oxygen consumption difference
for simultaneous determination was 7.1 ± 6.1
and 8.7 ± 6.7% for the total, and cerebral
vascular resistance difference was 7.5 ± 5.7%
for simultaneous determinations and 8.8 ±
8.3% for all 26.
Discussion and
Summary
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Previous comparisons of cerebral blood flow
measurements on the same patient using the
krypton 85 desaturation technique of McHenry l demonstrated a mean difference of
5.8 ± 3.8%. Similar comparison of this to the
argon mass spectrometer technique in this
study establishes that the two techniques are
comparable in measuring cerebral blood flow,
cerebral oxygen consumption, and cerebral
vascular resistance. In addition to this the
advantages of mass spectrometry are:
1. No blood need be withdrawn except for
arterial and venous volumes percent
determinations to calculate cerebral
oxygen consumption.
2. Personnel required for the procedure are
decreased by at least one-half.
3. Technical difficulties related to blood
withdrawal are eliminated.
4. Radiation precautions are not required.
5. Total time required for each procedure is
decreased.
6. Multiple studies may be performed
without affecting the patient.
7. The desaturation curve is observed at the
time of the study and, if unsatisfactory,
it can be corrected or repeated without
waiting for analysis.
Sfrok;
Vol. 3, May-Junt
7972
8. Partial pressures of oxygen and carbon
dioxide can be observed constantly and
breathing or other technical difficulties
can be recognized and corrected.
References
1. McHenry LC Jr: Quantitative cerebral blood
flow determination: Application of Krypton
85 desaturation technique in man. Neurology
(Minneap) 1 4 : 7 8 5 - 7 9 3 , 1964
2. Kety SS, Schmidt CF: The nitrous oxide
method for the quantitative determination of
cerebral blood flow in man; theory, procedure
and normal values. J Clin Invest 2 7 : 476-483,
1948
3. Dyken ML, Campbell RL, Frayser R: Cerebral
blood flow, oxygen utilization, and vascular
reactivity: Internal carotid artery complete
occlusion versus incomplete occlusion with
infarction. Neurology (Minneap) 20: 11271132, 1970
4. Brantigan JW, Gott VL, Vestal GJ, et a l : A
nonthrombogenic
diffusion
membrane
for
continuous in vivo measurement of blood gases
by mass spectrometry. J Appl Physiol 28: 375377, 1970
5. Wald A, Hass WK, Siew FP, et a l : Continuous
measurement of blood gases in vivo by mass
spectrography. Med Biol Eng 8: 11-128,
1970
6. Woldring S, Owens G, Woolford DC: Blood
gases: Continuous in vivo recording of partial
pressure by mass spectrography. Science 153:
885-887, 1966
7. Hass WK, Siew FP, Yee DJ: Progress and
adaptation of mass spectrometer to study of
human cerebral blood flow. Circulation 3 8 :
96, 1968
8. Pevsner PH, Bhushan C, Ottesen OE, et a l :
Cerebral blood flow and oxygen consumption:
An on-line technique. Johns Hopkins Med J
128: 134-140, 1971
285
Cerebral Blood Flow and Metabolism Studies Comparing Krypton 85 Desaturation
Technique With Argon Desaturation Technique Using the Mass Spectrometer
Mark L. Dyken
Stroke. 1972;3:279-285
doi: 10.1161/01.STR.3.3.279
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