Journal of Cerebral Blood Flow and Metabolism 11:1031-1035 © 1991 The International Society of Cerebral Blood Flow and Metabolism Published by Raven Press, Ltd., New York
Cerebral Blood Flow Reactivity to Changes in Carbon Dioxide Calculated Using End-Tidal Versus Arterial Tensions
William L. Young, *Isak Prohovnik, Eugene Ornstein, Noeleen Ostapkovich, and Richard S. Matteo Departments of Anesthesiology and *Psychiatry, Neurology, and Radiology, Columbia University College of Physicians and Surgeons, New York, New York, U.S.A.
Summary: We retrospectively examined arterial and end tidal estimations of CO2 tension used to calculate cere brovascular reactivity in 68 anesthetized patients. CBP was measured using the intravenous 133Xe technique at
+ 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-l min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either Paco2 ( 1.9 ± 0.8) or Pe,co2 ( 1.8 ± 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.9 1, p = 0.0001). The CBP re sponse to changes in CO2 tension can be reliably esti mated from noninvasive measurement of Pe,co2• Key Words: Carbon dioxide reactivity-Carbon dioxide ten sion-Cerebral blood flow.
mean ± SD P aco2 values of 28.2 ± 5.2 and 38.8 ± 4.8 mm Hg. The correlation between all Paco2 and end-tidal Pco2 (Pe,co2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between Paco2 and Pc,co2 (y = O.llx
Estimation of
P aco2
during CBF determination is
tively examined the correlation between arterial and end-tidal estimations of CO2 tension and the
a critical requirement for quantitative interpretation of results. Owing to the potency of
Paco2
in regu
relationship between the two methods to calculate
lation of vascular tone, neither comparative con
cerebrovascular reactivity to changes in
CO2,
trasts nor inferences regarding metabolic rates can be made with confidence unless this powerful co variate is taken into account.
METHODS
CO2 responsiveness is
Data were collected from 68 anesthetized patients en rolled in CBP research protocols (Young et a!., 1989, 1990) undergoing elective carotid endarterectomy (n = 16), resection of cerebral arteriovenous malformation (n = 45), or cervical or thoracic laminectomies (n = 7). No patient had clinically significant pulmonary disease. An esthesia was induced with thiopental 4 mg/kg and endo tracheal intubation was facilitated with a nondepolarizing muscle relaxant. Anesthesia was maintained with 0.751.0% isoflurane in nitrous oxide and oxygen. Standard capnography (Hewlett Packard Capnometer 472IO-A) and arterial blood gas analysis were employed using daily rou tine clinical calibration procedures. CBP was measured with a Cerebrograph lOa (Novo Diagnostic Systems, Bagsvaerd, Denmark) using the intravenous 133Xe tech nique as previously reported (Young et a!., 1988-90). During stable levels of anesthesia, a baseline CBP mea surement was obtained. The Pe,co2 was then increased 10 mm Hg by addition of carbon dioxide to the inspired gas mixture. After a period of � 10 min of a stable P e,co2 level, CBP was again measured. Pe,c02 levels were ver-
particularly important in the assessment of cerebro vascular reserve in ischemic vascular disease (Bul lock et aI., 1985). However, direct measurement of
Paco2
requires arterial puncture and is most often
avoided in favor of monitoring noninvasive end tidal
CO2
tensions
(Petco2).
The convenience and
safety of noninvasive monitoring should, however, be weighed against its precision as an estimate of arterial
CO2
tension. In this study, we retrospec-
Received January 30, 1991; revised May 3, 1991; accepted May 7, 1991. Address correspondence and reprint requests to Dr. W. L. Young at Department of Anesthesiology, Columbia-Presbyterian Medical Center, Neuroanesthesia-AP 901, 161 Fort Washington Ave., New York, NY 10032, U.S. A.
Abbreviations used: ANOVA, analysis of variance; Pa_eco2, difference between arterial and end-tidal Pco2; Pe,co2, end-tidal
Pco2·
1031
1032
W. L. YOUNG ET AL.
ified by arterial blood gas determination for P aco2' The two measurements at different levels of Paco2 were used to calculate CBF reactivity. The CBF data are expressed as the Initial Slope Index (ml 100 g -1 min -1 ) , assuming a Xe blood-brain partition coefficient of unity for the per fused tissue (Risberg et aI., 1975; Prohovnik et aI., 1983, 1985). The mean of up to 10 CBF detectors covering both middle cerebral artery supply territories was taken as an index of global CBF. The global CBF reactivity to carbon dioxide was calculated as the absolute increase in CBF in per millimeter mercury change in PaCoZ (ml 100 g -, min-' mm Hg-'). Decreasing temperature results in increased CO2 solu bility in blood; therefore, use of non-temperature corrected values will tend to overestimate the true Paco2 (Severinghaus et aI., 1957). Since the Paco2 values were measured and reported at 37°C, the influence of patient temperature was examined using the formula shown in Eq. 1 (Bergman, 1968) where T, is patient temperature and T2 is the temperature at which the blood gas machine measures COz tension; Pcoz (T,) is therefore the cor rected value and Pco2 (Tz) is the measured (uncorrected) value at 37°C:
(1)
(>65 years). Data were compared by linear regres sion or by analysis of variance (ANOYA); if an ANOY A was significant, differences between groups were isolated by Fisher's progressive least significant differences test. The threshold for signif icance was taken as p < 0. 05. All values are ex pressed as means ± SD.
RESULTS For the complete group of 68 patients, the base line
Paco2
was 28.2 ± 5. 2 mm Hg versus a temper
ature-corrected value of 25. 9 ± 4.9 mm Hg (p
=
0.001). However, the correlation between the two = 0.93x - 0.46; r = 0.98, p 0. 0001) and use of the corrected versus uncor
values was excellent (y =
rected values had no influence on the various sta tistical analyses. We have therefore presented the uncorrected values below, unless otherwise indi cated. Physiologic data for the three surgical subsam pIes, representing the baseline and CO2 challenge CBF measurement periods, are presented in Table
1. There were differences between the three groups The difference between simultaneous measure
ment of Paco2 and P etC02 (Pa_eC02) was calculated at each CBF measurement. For the purpose of analy
of surgical patients. Primarily, the carotid endar terectomy patients were older, were managed at a significantly higher level of Paco2' and had a higher
sis, patients were divided into three groups: young
MABP than the younger craniotomy and laminec
(20-44 years), midage (45-65 years), and elderly
tomy patients.
± SD) from three groups of surgical patients: carotid endarterectomy (CEA), craniotomy for arteriovenous malformation resection (A VM), and cervical or thoracic laminectomy
TABLE 1. Physiologic data (mean
CEA (n Age (yrs) pH
PetCOZ (mm Hg)
Baseline C02c Baseline C02e Baseline
PaOZ (mm Hg)
COz" Baseline
Hemoglobin (mg/dl)
COz Baseline
MABP (mm Hg)
COz Baseline
Temperature eC)
COz Baseline
CBF (ml lOO g-l min-I)
COz Baseline
Pa--ecoz (mm Hg)
CO2' Baseline
PaCOZ (mm Hg)
COz
PaCOZ slope of CBF response (ml 100 g-l min -, mm Hg-') PetCOZ slope of CBF response (ml 100 g-' min-, mm Hg-')
67 7.42 7,35 35,7 45.4 27 38 192 189 13.2 \3,3 99 95 35,5 35,6 22 40 9 8
=
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
16) 10 0,05 0,05 4.2 4.4 4 6 36 28 2.0 1.9 12 10 0.6 0.6 8 12 2 3
AVM (n
36 7,50 7,38 25.5 36.6 21 32 224 181 12,3 12.5 79 82 35.2 35.3 22 43 5 5
=
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
45) 1O",b 0,04a,b 0,04a 2.5",b 2.5" 2",b 2" 27 36 2.0 1.9 8",b 9" 0.7 0.7 4 II 2a 2a
Laminectomy (n = 7)
45 7.46 7.37 28,5 37.9 24 34 197 192 13.2 \3.3 87 85 35.7 35,8 23 41 4 4
± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±
10" 0,03" 0,02 2,2" 2.6" 2" I" 37 28 2.0 2.0 9" 3" 0.5 0.5 6 5 2a 2a
1.9 ± 0,9
1.8 ± 0,9
2.1 ± 0.8
1.7 ± 0,8
1.8 ± 0.9
1.9 ± 0.6
Differences between groups were tested by analysis of variance and, if significant, by Fisher's progressive least significant differences test. PetCOZ' end-tidal Pcoz; Pa--ecoz, difference between arterial and end-tidal Pcoz' a Significantly different from the CEA group, p < 0.05, b Significantly different from the laminectomy group, p < 0.05, e All groups significantly different from baseline, p < 0.05,
J Cereb Blood Flow Metab, Vol,
11,
No, 6,
1991
ARTERIAL/END-TIDAL CO2 RELATIONSHIP
Paco2
The correlation between all measured
Petco2 values is shown in Fig. 1 (y
and
y
0.85x - 0.49; 0.0001). As shown in Fig. 2, there
14
was a moderate correlation between advancing age
12
r
=
0.93, p
=
and an increase in
0.73, p
Pa_eco2 (y
=
0.1 1x
=
0.79;
+
r
=
0.0001). Cerebrovascular reactivity to I I 1 changes in CO2 (ml 100 g- min- mm Hg- ) was similar (p = 0.358) when calculated by using either Paco2 ( 1.9 ± 0.8) or Petco2 (1.8 ± 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001) and is shown in Fig. 3. There was no influence of =
Q)I I �E E a..�
0.002x - 0.06;
r
0.104, p
=
age groups had significantly different =
(p
Pa_eco2 levels
0.0001). However, there was no difference
0.73
6 • o
2 o
c
10
20
T
c
30
40
60
50
70
SO
CEA AVM Laminectomy
90
Age
Pa_eco2 at baseline and during CO2
challenge as the within-group repeated measure, all
=
..
two-way ANOV A with age group as the between group factor and
r
0.79,
S
0.659). By
=
+
4
activity calculated with arterial or end-tidal values =
0.11x
10
C\I
o OOi
age on the difference between cerebrovascular re
(y
=
1033
(yrs) Paco2 and
end-tidal Pco2 difference as a function of age. CEA, carotid endarterectomy; AVM, arteriovenous malformation.
FIG. 2. Scattergram of
(Pa.eC02)
between baseline and CO2 challenge values within each age group. The mean
Pa_eco2
values for the
nia. Use of temperature correction to adjust for the
young, midaged, and elderly groups for the baseline
difference in patient temperature and the tempera
measurement were 4 ± 2, 6 ± 2, and 9 ± 3 mm Hg.
ture at which the
Paco2
was actually measured re
vealed that, in the temperature range studied, abso
Paco2
lute
DISCUSSION
levels were overestimated by �9%.
However, since patient management was based on In this study we have demonstrated that there is a good correlation between arterial and end-tidal
the uncorrected values and the whole sample was studied in the same temperature range, use of the
estimates of Paco2 and, most importantly, that there
correction factor adding nothing to the interpreta
is a close correlation between the calculated slope
tion of the results, and we have therefore presented
of the CBF response to changes in either
only the measured
PetCo2'
Paco2
or
Further, as demonstrated in Fig. 1, the cor
relation between
PetC02
and
Paco2
appears to be
similar during both hypocapnia and mild hypercap-
50
=
0.S5x - 0.49,
r
=
v
,
v
v,'
�
,/
"
.s; .;:::;
;I
(J � Q) a:
v
-: ., """,, ' " ;""..J: c �w.,,� v ,
OI +-'E E 30 Q) ._ 0...
C\I
0 0
c
.,wyt v vv v 'v ,/ ov D c'" COCCDV ,"0 00
� '0
C
cifCan c
QID:IJ 20 cc,'P:'� � C
C
..�[][]c
o
Baseline
V
C02 challenge
PaC02 (mm Hg) PaC02 for
all patients.
0.86x
+
0.23.
r
0.91
=
C 4
c
3
v
c c
2
05'c
•
c
c
CC
o 0 •
I
---�
FIG. 1. Scattergram of end-tidal
=
.;:::;
15 �20 25 30 35 40 45 50 55
of
it does not appear to affect the compa-
+-'
v v�'
OOl 35
25
Pa_eco2,
>-
v
40
data.
5
0.93
45 C\J
of
y y
Paco2
Although advancing age affects the absolute level
Pco2 (PetC02)
o
'0 C ill
T
CEA AVM Laminectomy
0 0
2
3
4
Arterial C02 reactivity FIG. 3. Scattergram of CBF reactivity to changes in carbon
as a function
dioxide calculated using either end-tidal Pco2 values (y-axis) or P cO2 values (x-axis). Units are ml 100 g-1 min-1 mm Hg-�. CEA, carotid endarterectomy; AVM, arteriovenous malformation.
J Cereb Blood Flow Metab, Vol. 11, No.6, 1991
W. L. YOUNG ET AL.
1034
rability of CBF response slopes calculated using
ported mean P a_eco2 values of 4. 5 mm Hg during
measured, regardless of the degree of age-related
4. 7 mm Hg during mechanical ventilation (Paco2 = 32. 9 mm Hg), similar to the Pa_eco2 found in the
pulmonary dysfunction. The correlation between
present study.
Paco2 or PetC02' This is presumably attributable to a stable Pa_eco2 gradient in the range of CO2 values
spontaneous ventilation (Paco2 = 5 1. 7 mm Hg) and
advancing age and decreased pulmonary function is
The results of this study may not be directly ap
well described (Kohn, 1963). Pulmonary function
plied to the awake state. However, if one assumes
becomes progressively compromised with increas
that anesthesia is a "worst case," then the changes
ing age, involving respiratory mechanics, lung vol
in both Paco2 and PetC02 relative to one another
ume, and gas exchange. Despite the widening
appear to be similar and it is reasonable to conclude
appear to be any influence of age on the agreement
in CO2 tension can be reliably estimated from non
between arterial and end-tidal calculations of cere
invasive measurement of
Pa_eco2 gradient with advancing age, there did not
that the true slope of the CBF response to changes
Petco2.
brovascular reactivity, because both normocapnic and hypercapnic levels were equally affected. An issue that this study did not address is the 133 errors inherent in using the intravenous Xe method where end-tidal gas is sampled to estimate the arterial input function to deconvolute the head curves. As most recently described by Hansen et ai.
(1990), an increased pulmonary dead space will re sult in an underestimation of the arterial input func
Acknowledgment: This work was supported in part by NIH ROI-NS277 13 to Dr. Young. The authors wish to thank Angela Wang for expert technical assistance, Joyce Ouchi for assistance in preparation of the manuscript, and Drs. J. W. Correll, D. O. Quest, B. M. Stein, and R. A. Solomon in the Department of Neurological Surgery and Dr. T. A. Wang and P. O. Alderson in the Department of Radiology for their cooperation in performing these stud ies.
tion and therefore of true CBF. However, this ef
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