-
ARTERIAL BLOOD GASES AND ACID-BASE BALANCE INCYANOTIC CONGENITAL
HEART DISEASE'BY MINERVA MORSE AND DONALD E. CASSELS 2
(From the Department of Pediatrics, University of Chicago
Clinics, Chicago, Illinois)
(Submitted for publication April 16, 1953; accepted May 15,
1953)
The purpose of this report is to present dataconcerning the
arterial blood gases and the acid-base balance in patients with
cyanosis due to con-genital heart disease. Since the study is
relatedto cyanosis and abnormalities of the blood con-sequent to
this, no distinction is made betweenthe various anatomical defects
producing cyanosis.
Compensatory or adaptive mechanisms in thepresence of cyanosis
related to congenital heartdisease have been the subject of a
number ofstudies (1-6). The present study was undertakento obtain
further information concerning the ar-terial blood gases in this
disease, especially in re-lation to age and in respect to the
influence ofarterial unsaturation on the acid-base balance.
Sixty cyanotic patients were studied, varying inage from 1 to 36
years. The methods used havebeen described in a preceding report
(7).
RESULTS
Because age has been found to affect the concen-trations of the
blood gases (7), especially the HbO2capacity, the CO2 content and
the alkaline reserve,it was necessary to evaluate the results for
an indi-vidual of a given age in terms of deviations from themean
values for that age. Normal values for chil-dren of different ages
are given in the preceding re-port (7). Table I gives the results
of single tests oneach of 60 patients with cyanotic congenital
heartdisease, in terms both of absolute values and ofdeviations
from the normal. In Figures 1 and 2deviations from the normal are
plotted for eachage group against a background which representsthe
range of variation found in normal, healthyindividuals of the same
age group. Table II givesthe results of repeated tests on seven
individuals.It includes cases of pulmonary stenosis in which
I This work was conducted under a grant from theDouglas Smith
Foundation at the University of Chicago.2Present address: Bobs
Roberts Memorial Hospital,
920 East 59th Street, Chicago, Ill.
pulmonary blood flow was increased by aortic-pulmonary artery
anastomosis or pulmonaryvalvulotomy.
Certain differences in distribution with respectto age are
evident in the data of Table I andFigures 1 and 2. Arterial oxygen
saturation be-low 50 per cent was found only in children of 7years
and younger. The fact that all but one ofthe adults had arterial
saturations above 79 percent is misleading and an artifact of
sampling.Of the adult group only one was believed to havepulmonary
stenosis. It should be noted that inthe reports of Talbott et al.
(1), Bing, Vandam,and Gray (8), and Suarez, Chiodi, Fasciolo,
andTaquini (3), of 33 patients with cyanotic con-genital heart
disease who were over 18 years ofage, 15 were found to have
arterial saturationsbelow 75 per cent. However, only one of
thesepatients had a saturation below 60 per cent. Thegreat majority
of patients of our study who hadHbO2 capacities within the normal
range wereyounger children. On the other hand, the ma-jority of
very high HbO2 capacities, over 32 vol.per cent, were found in
older children and adults.One child of 6 years was found to have a
HbO2capacity of 32.5 vol. per cent. In regard to thealkaline
reserve of the plasma there seems to be nospecial trend with age.
The lowest values werefound in children of 7 and 8 years. It may
besignificant that in spite of the fairly high arterialoxygen
saturations found in the adults of thisstudy, all values for
alkaline reserve were belowthe normal range of variation. In the
case of thearterial pCO2, about a third of the children of 12years
and younger had values above the normalmean, whereas in children
above that age and inadults all values but one lay below the
normalmean. The great majority of the lower thannormal pH. values
were found in children between6 and 10 years.
Since the data of Table I are arranged in theorder of increasing
arterial saturation, it can be
837
-
MINERVA MORSE AND DONALD E. CASSELS
TABLE IOxygen saturation, HbO2 capacity, pkssma CO2 T4o0* pCO2
and pH. of arterial blood of patients with
cyanotic congenital heart diseaseHbO2 capacity
Dev.Arterial Value from
Age Sex saturation found normalyr. per cent Vo. % Vol. %2 F 21.0
14.5 - 2.02 M 21.4 28.6 +12.11 F 21.6 18.0 + 1.56 M 40.5 28.6 +
10.27 M 40.6 31.1 +12.72 M 41.7 25.6 + 9.12 M 46.9 14.0 - 2.54 F
49.8 30.9 +13.2
14 M 52.0 33.8 +15.49 M 58.7 32.8 +14.415 M 59.1 35.1 +16.77 F
61.8 26.6 + 8.26 M 63.2 28.4 +10.036 F 63.4 35.1 +14.614 F 65.4
32.4 + 14.06 M 65.6 32.5 +14.110 F 65.7 25.0 + 6.63 F 68.3 19.7 +
2.04 M 68.6 29.9 +11.55 M 70.4 27.8 + 9.47 M 70.6 27.8 + 9.4
17 M 71.2 26.4 + 6.710 M 72.1 27.3 + 8.913 M 72.2 22.7 + 4.32 M
73.0 16.6 - 0.15 F 73.3 21.0 + 2.6
10 M 74.2 31.2 +12.88 M 74.3 28.1 + 9.72 M 74.9 19.1 + 2.65 F
75.4 22.7 + 4.34 M 76.8 24.6 + 6.910 M 77.0 36.5 +18.16 M 77.4 17.4
- 1.0
24 F 79.0 22.7 + 2.211 M 79.3 25.3 + 6.935 F 79.4 29.1 + 8.625 M
79.7 25.7 + 5.231 M 79.9 22.6t + 2.14 M 80.0 18.2 + 0.58 M 80.7
24.6 + 6.27 F 80.8 23.9 + 5.516 F 81.0 26.2 + 7.019 M 82.4 35.7
+15.28 M 82.8 22.5 + 4.15 F 83.6 23.8 + 5.4
23 F 83.8 25.2 + 4.712 M 84.9 22.5 + 4.19 M 85.9 21.6 + 3.210 F
87.1 20.0 + 1.612 M 88.0 21.6 + 3.231 M 89.0 28.5 + 8.012 F 89.8
17.2 - 1.225 M 89.9 24.4 + 3.916 M 90.1 27.9 + 8.29 F 90.5 18.4
0.09 M 90.8 18.4 0.010 M 91.7 21.1 + 2.74 F 91.7 17.2 - 0.54 M 91.9
18.6 + 0.29 M 92.7 26.1 + 7.7
Plasma C02 Tso*Dev.
Value fromfound normaloi. % Vol. %37.3 -11.137.4 -11.039.6 -
8.835.7 -18.934.6 -20.037.3 -11.142.6 - 5.841.5 -12.043.3 -12.233.6
-21.041.6 -13.945.3 - 9.340.8 -12.745.6 -12.641.2 -14.342.4
-11.150.6 - 4.043.6 - 4.846.4 - 7.149.4 - 4.145.9 - 8.749.5 -
6.349.0 - 5.654.2 - 1.349.1 + 0.745.9 - 7.646.2 - 8.448.9 - 5.743.6
- 4.845.5 - 8.042.5 -11.043.8 -10.849.6 - 3.955.5 - 2.946.1 -
9.448.0 -10.252.2 - 6.050.9 - 7.341.1 -12.448.6 - 6.943.7 -10.945.6
- 9.947.6 -10.649.3 - 5.349.2 - 4.351.5 - 6.747.6 - 7.050.9 -
3.746.6 - 8.155.6 + 1.051.6 - 6.652.7 - 2.854.3 - 3.950.0 - 5.548.7
- 5.952.3 - 2.453.0 - 1.653.0 - 0.547.1 - 6.448.6 + 0.2
Arterial pCO2Dev.
Value fromfound normalmm. mm.41.7 + 4.440.2 + 2.942.1 + 4.837.8
- 0.235.9 - 2.135.0 - 2.325.5 -11.839.3 + 2.040.8 - 0.538.3 +
0.331.6 - 9.737.9 - 0.132.9 - 4.430.2 -10.932.8 - 8.541.6 + 4.339.5
+ 1.540.7 - 3.429.4 - 7.934.5 - 2.837.8 - 0.229.7 -11.633.4 -
4.627.5 -13.832.4 - 4.929.4 - 7.938.4 + 0.439.4 + 1.434.7 - 2.637.7
+ 0.435.2 - 2.127.7 -10.344.7 + 7.428.5 -12.634.4 - 3.646.8 +
5.734.3 - 6.838.8 - 2.323.5 -13.834.5 - 6.833.1 - 4.934.4 - 6.737.2
- 3.929.5 - 8.534.7 - 2.633.7 - 7.430.0 - 8.035.9 - 2.142.2 +
4.226.5 -11.537.1 - 4.034.0 - 4.037.9 - 3.233.5 - 7.840.2 + 2.245.7
+ 7.732.8 - 5.243.7 + 6.439.7 + 2.428.7 - 8.6
Arterial pHsDev.
Value fromfound normal
7.227 -.1227.266 -.0837.257 -.0927.244 - .1557.244 -.1S57.279
-.0707.423 +.0747.297 - .0937.308 -.0737.203 -.2017.348 -.0337.334
-.0657.322 -.0777.399 -.0037.328 -.0537.283 -.1077.369 -.0347.289
-.0607.407 +.0177.392 +.0027.333 -.0667.434 +.0537.398 -.0067.502
+.1217.407 +.0587.401 +.0117.333 - .0717.351 - .0537.330 -
.0197.328 - .0627.313 - .0777.391 +.0137.311 -.0927.496 +.0947.355
-.0497.296 - .1067.408 +.0067.367 -.0357.412 +.0227.379 - .0027.340
- .0017.351 - .0307.352 - .0297.429 +.0257.377 - .0227.407
+.0057.407 +.0037.387 -.0177.298 - .1057.519 +.1167.380 - .0227.421
+.0227.399 -.0037.394 +.0137.330 - .0747.323 - .0807.428 +.0257.340
-.0507.317 -.0737.420 +.016
No. Subject
1 S.D.2 R.E.3 P.S.4 R.B.5 J.M.6 J.A.7 H.R.8 J.G.9 M.P.10 J.W.11
S.X.12 V.S.13 W.B.14 M. M.15 L.C.16 C.F.17 J.R.18 V.J.19 N.H.20
A.F.21 B.G.22 L.S.23 J.S.24 B. M.25 C.L.26 P. M.27 S. D.28 R. B.29
R.J.30 P. K.31 R.F.32 R. D.33 R. M.34 L.Z.35 E.V.36 G.H.37 R.G.38
G. N.39 C.L.40 D. R.41 S.L.42 M.C.43 D. B.44 D. M.45 J.T.46 I. B.47
A.G.48 C. K.49 M. M.50 J. M.51 B.Z.52 M. D.53 P.T.54 B. N.55 P.
B.56 W.G.57 B.V.58 P.C.59 R.W.60 T.A.
* Plasma C2 T40, or alkaline reserve, is defined as the CO2
content of plasma from fully oxygenated blood whichhas been
equilibrated with CO2 at a tension of 40 mm. Hg.
t The moderately low HbO2 capacity in this case is due to
repeated phlebotomy.
838
-
BLOOD GASES IN CYANOTIC CONGENITAL HEART DISEASE
0
0~~~~~
W...:.y.. :.:..I,....: .' .......'.-.':"" ,.,....,..,.-
0~~~~~~~~
1-2 3-4 5-14 15-1 ADUL. "MNYEAR S ALT.
.20-
+15-
+10-
I-
:
41
-!O-
-15-
0
1-2
%
.. ...............
. " .,.......
.. ...,. .... ...,.--. ........
3-4 6-14YEARS
0
I
00
00
00
.......
,..........I
.
0*
.... ....
.........
..........
.. ..i. ..
..........
o-17 ADULTS.RE S.ALT.
1-4 5-6 7-I ADULTSREHYEARS ALL
FIG. 1. ARTERIAL HbO, CONTENT, HbO, CAPACITY, AND PERCENTAGE
OXYGEN SATURATION OF THEBLOOD OF PATIENTS WITH CYANOTIC CONGENITAL
HEART DISEASE, SHOWN AS DISTRIBUTIONS OF THEDEVIATIONS FROM THE
NORMAL MEAN FOR THE VARIOUS AGE GROUPS
seen that rough relationships exist between thedegree of
arterial unsaturation and the extent ofthe deviations of the HbO2
capacity, alkaline re-serve and arterial pH. from the normal
mean.These relationships are more clearly apparent inTable III
which gives mean values for the threegroups into which the material
was divided onthe basis of arterial unsaturation. The moremarked
deviations from the normal tend to occurin patients with arterial
saturations below 70 percent. In each group there are marked
exceptions.The acid-base balance of the arterial blood of
patients with cyanotic congenital heart disease isshown in
Figure 3, in which the individual datafor (HCO8)S, pCO2 and pH. are
plotted ontriaxial charts according to the method of Hast-ings and
Steinhaus (9) and of Shock and Hast-ings (10). The shaded area in
each chart repre-sents the range of variation which we have
foundfor normal healthy children of corresponding age
groups and for adults (7). It is evident that inthe great
majority of cases the acid-base balancemay be described as that due
to fixed acid excessor to a combination of fixed acid excess and
CO2deficit.Data concerning serum chloride, protein and
lactic acid were obtained for 15 of the patientswith cyanotic
congenital heart disease in the hopesof observing changes in the
electrolyte balance ofthe serum which might compensate for the
re-duced bicarbonate concentration. The data in-clude two
independent determinations on three ofthe patients, in one case
separated in time bythree years. The results in Table IV show
thatin half of the cases the sum of the three ions whichconstitute
the great part of the anion moiety ofthe serum electrolytes,
bicarbonate, chloride, andproteinate, falls within the normal range
of varia-tion, while in the other half the sum of the threemajor
anions is below normal. The table shows
839
z
z0.C)W0
'1
4
I
--
-
MINERVA MORSE AND DONALD E. CASSELS
clearly that the difference in the sum of the threeanions is due
almost entirely to a difference in themean chloride level. Thus, in
approximately halfof the cases a reduction in the bicarbonate level
isalmost balanced by a rise in the serum chloridelevel, but in the
other half there is no apparentrise in chloride concentration.
Those in the groupwithout chloride compensation tend to have
lowersaturations and higher HbO2 capacities, althoughthe values of
the two groups overlap. The meanpH. of the group without chloride
compensationis 7.332 as compared with a mean value of 7.382for the
other group, but the low mean pH5 of theformer group is due to
lower than normal valuesin only half of the group. The blood
lactate con-centration of the group without chloride compen-sation
is not significantly higher than in the othergroup.
In Figures 1 and 2 the last column of eachgroup contains
corresponding data for residents
at high altitude, taken from the reports of Dill etal. (11-13)
and of Hurtado and Aste-Salazar(14). The triangles and squares of
Figure 3 alsoshow these data. They are given for the purposeof
comparison since both residents at high altitudeand patients with
cyanotic congenital heart diseaserepresent hypoxic states to which
the individualhas become acclimatized over a long period oftime.
Both groups show approximately the samedegree of arterial
unsaturation, although thespread of values in cyanotic congenital
heart dis-ease is greater and much lower values are some-times
found. Figure 2 shows that the alkalinereserve of the plasma tends
to be lower in resi-dents at high altitude than in patients with
cyanoticcongenital heart disease. Table III includesdata for
residents at high altitude in terms of meandeviations from the
normal. Of the three groupsof patients with cyanotic congenital
heart diseasewhich are shown in this table, the second group,
z +5-0
z
0-
_ -F0
-i
4I-49
-10-
-15-
-20-
1-4 5-6 7-11 12-rTA0U S RES.YEARS ALT.
0* *
.t.y@*,.'..... ... .
4...........*.... +**. *
..... '..... ,. ..
,'..'.... ,, K ''
....w.... ,.,...,..,.,-..*SX*s* e.
....- -....... ..
-::.E....-::..
*
*0 00
-
0.....
0....
1-6
*.......
..v.....
...........
,...............
...v.......
.... ....
....-......
0x,....
0
.
0
'..:v'g3..
...v.x...-.......
x...x... 3.
0.0-
+.15-
+.10-
*.os
0
I 0--i4
IdI--S
KI-.10-
-.15-
-.20-
7-12 13-I7 ADULTS RES.YEARS ALI
l* 0-* *
s* 0e*
t-:.;.:4.'.-,..':.:., :s:,., * -..
[wy * 0~fe *
........: .
,.,.,.,......
..
......
3.. .0 _
.....0............. ....
1-3 4-5 6-2YIEARS
FIG. 2. PLASMA CO2 T., ARTERIAL pCO,, AND ARTERIAL pH. OF
PATIENTS WITHCYANOTIC CONGENITAL HEART DISEASE, SHOWN AS
DISTRIBUTIONS OF THE DEVIATIONSFROM THE NORMAL MEAN FOR THE VARIous
AGE GROUPS
840
0
CM
0
U41
0.
...:-y:.:.]
sS
:::..........
[........l.:..... .14.
..'' '14..
[..::.....1K -: .:.::1
W. -..-......
[..-.......
E S9*'
I *0
jiI37AOUt* RES.HIGH
ALT.
iL--I
....
.......
*......
,..:..........
x--,. .vv
:'.'v
......
*x..
i
-
BLOOD GASES IN CYANOTIC CONGENITAL HEART DISEASE
TABLE II
Results of repeated tests on the same individual
Arterial HbO Plasma* Arterial ArterialNo. Date Subject Age Notes
saturation capacity CO2T4o pCO2 pHs
5 2-25-429- 8-4312- 3-464-22-47
Post-op.,5-14-473-10-49
17 10-14-47Post-op.,11-18-47
22 4-11-52Post-op.,10-15-52
27 6-12-4410-11-4610-17-4610-28-4612-12-469- 9-47
Post-op.,10- 8-4712- 8-473- 8-49
28 5- 5-47Post-op.,5-23-478-20-52
29 1-10-49Post-op.,2- 4-49
50 12-11-471-18-494- 2-51
Post-op.,6-29-51
J. Mu.
J. R.
L. S.
S. D.
R. B.
R. J.
Yr. Mo.2 74 27 47 97 109 8
Aortic-pulmonary arteryanastomosis, 4-24-47
9 8 Blalock anastomosis, 3-29-47Obliteration of anastomosis,
9 9 10-17-47
16 1017 48 010 410 410 510 611 311 411 612 98 08 113 22 0
2 1
J. Mr. 10 1011 1114 114 4
Pulmonary valvulotomy, 4-14-52
Phlebotomy, 10-24-46Iron medication begun
10-30-46Aortic-pulmonary artery
anastomosis, 9-14-47
Aortic-pulmonary arteryanastomosis, 5-47
Aortic-pulmonary arteryanastomosis, 1-11-49
Pulmonary valvulotomy, 6-13-51
per cent54.954.240.653.1
72.275.2
wl. %27.131.431.127.923.925.7
vol. %41.740.034.633.5
47.053.0
mm. Hg43.447.735.940.8
44.934.7
7.2667.2327.2447.186
7.2957.422
71.8 18.7 54.6 47.3 7.34065.7 25.0 50.6 39.5 7.369
71.2 26.4 49.5 29.7 7.43496.6 19.7 57.0 48.6
7.38768.870.874.262.666.177.184.383.883.2
31.531.131.127.429.427.924.025.426.0
47.142.746.249.342.847.052.451.453.4
34.736.338.439.035.233.933.531.432.4
7.3737.3147.3337.3657.3257.3727.4227.4317.438
74.3 28.1 48.9 39.4 7.35177.6 21.9 52.3 33.3 7.42674.1 24.2 47.6
30.2 7.40174.9 19.1 43.6 34.7 7.33076.8 16.4 47.5 31.1
7.40384.088.081.095.1
22.021.623.120.9
51.755.654.953.6
30.126.537.139.7
7.4477.5197.4157.375
* Plasma CO2 T40, or alkaline reserve, is defined as the CO2
content of plasma from oxygenated blood which hasbeen equilibrated
with CO2 at a tension of 40 mm. Hg.
with arterial saturations of 70 to 88 per cent,compares well in
arterial saturation with residentsat high altitude. It is evident
that for comparabledegrees of arterial unsaturation the blood of
resi-dents at high altitudes has a slightly higher HbO2capacity, a
much lower alkaline reserve andarterial pCO2, and a slightly lower
pH.. Theacid-base picture in Figure 3 is quite similar inboth
groups, i.e., a combination of fixed acid ex-cess and CO2
deficit.The post-operative results in Table II give
information as to the effects of increased pul-monary blood flow
on the arterial blood gases andthe acid-base balance. In four cases
of Tetralogy
of Fallot, two, J. Mu. and S. D., showed markedimprovement in
arterial saturation, but littlechange was observed in R. B. and R.
J. Notshown in the table is the fact that R. J. showedmarked
clinical improvement and little evidenceof cyanosis when seen four
years later. L. S. andJ. Mr., who had diagnoses of pulmonary
stenosisand atrial septal defect, showed arterial satura-tions of
96.6 and 95.0 per cent respectively follow-ing valvulotomy. A
reduction of HbO2 capacityoccurred in all cases. Those patients who
had amarked rise in arterial saturation also showed amarked rise in
the alkaline reserve of the plasma.In the cases of J. Mu. and S. D.
the alkaline re-
841
-
MINERVA MORSE AND DONALD E. CASSELS
TABLE III
Relation of the degree of arterial unsaturation to the
deviations from the normal of the Hb02 capacity and the acid base
balanceof the blood of patients with cyanotic congenikal heart
disease-a comparison of these deviations from
the normal with comparable values in native residents at high
altitude*
Mean deviations from the normal meanArterial
No. of saturation HbO2 capacity Plasma C02 T4ot Arterial pCO2
Arterial pHscases per cent vol. % vl. % mm.
Patients with cyanotic congenital heart disease10 93-88 + 2.9 4
1.21t -3.5 4 0.79 -1.4 4 1.81 -0.023 4 0.013631 88-70 + 5.8 i 1.31
-5.4 4 1.18 -4.6 4 1.29 -0.010 d 0.010412 70-40 +12.9 1 0.72 -13.8
4i 1.72 -3.1 1.44 -0.083 4 0.0185
Residents at high altitudes15 85-68 + 8.5 41 0.95 -13.2 :1 0.73
-8.4 :1= 1.19 -0.043 :1= 0.0106
* Data for residents at high altitude are taken from the reports
of Dill et al. (11-13) and of Hurtada and Aste-Salazar(14).t Plasma
CO2 T40, or alkaline reserve, is defined as the CO2 content of
plasma from fully oxygenated blood which
has been equilibrated with CO2 at a tension of 40 mm. Hg.t The
figures following the 4 signs represent the standard error of the
mean.
serve of the plasma rose to levels within the nor-mal range in
spite of the fact that their arterialblood still contained a
considerable degree ofvenous admixture. Their pH. levels, which
pre-viously had been consistently low, rose to normallevels after
an aortic-pulmonary artery anastomo-sis had been made. In the case
of J. R. the pre-operative values are comparable to the
post-operative values in the other patients. A Blalockanastomosis
had been performed some time beforebut cardiac decompensation
followed. Subsequentsurgical obliteration of the anastomosis
reducedthe arterial saturation, raised the HbO2 capacity,and
decreased the alkaline reserve of the plasma.It also reduced the
arterial pCO2 which presum-ably had been high because of pulmonary
conges-tion.
DISCUSSION
The fact that the great majority of patients withcyanotic
congenital heart disease have a normal orhigher than normal
arterial oxygen content isdue to the fact that the great majority
have a highHbO2 capacity. The high arterial oxygen con-tent loses
much of its value in the presence of re-duced arterial saturation
since the arterial oxygentension rather than its concentration
determinesthe level of the mean capillary oxygen pressureand the
resultant pressure gradient or diffusionpressure head between
capillaries and tissues.Studies of cyanotic congenital heart
disease byBing et al. (2) and Ermsting and Shephard (6)
have emphasized the great part played by thesigmoid shape of the
oxygen dissociation curve inreducing the arterial-mean capillary
oxygen ten-sion gradient, in contrast to the small effect of
thegreatly increased HbO2 capacity. The latter ex-erts its effect
on the mean capillary oxygen pres-sure by raising the venous level
of saturation since,of two bloods equally saturated, the one with
highHbO2 capacity will remain more highly saturatedafter equal
quantities of oxygen per unit of bloodhave been transferred to the
tissues.
It is of interest to find that 12 patients withcyanotic
congenital heart disease, or 20 per centof the number studied, did
not have an elevatedHbO2 capacity. Half of these had mild
cyanosisand arterial saturations between 87 and 92 percent. The
majority of the remainder were infantsnot over 2 years of age. The
fact that bloodcounts in these infants showed elevated values,with
red cell counts of 6.2 to 8.5 million per cu.mm., suggests that the
low HbO2 capacity is dueto a nutritional deficiency. Administration
of fer-rous sulfate to one infant raised his HbO2 ca-pacity.
Talbott and associates' (1) summary ofthe literature shows several
cases of congenitalheart disease in which the blood HbO2
capacitywas not elevated. Burchell, Taylor, Knutson, andWood (4)
have also noted a case with 68 percent saturation and with an HbO2
capacity ofonly 15.2 vol. per cent.The arterial saturation found in
patients with
cyanotic congenital heart disease covers a wide
842
-
BLOOD GASES IN CYANOTIC CONGENITAL HEART DISEASE
range. Eight cases showed arterial saturationsbelow 50 per cent.
It is probably significant thatsaturations below 25 per cent were
found only ininfants and that no saturation below 50 per centwas
observed in children over 7 years of age. Avery low arterial
saturation suggests a poor prog-nosis unless remedial operative
procedures canbe used. Operation was attempted in the case oftwo
infants with arterial saturations below 25 percent but death
followed. The third infant withthis low saturation survived only a
few monthsafter she was studied. Autopsy revealed trans-position of
the great vessels. There is suggestiveevidence that correction of
the iron deficiencypresent in cyanotic infants with low HbO2
ca-pacity improves their status.We believe that many of the
saturation values
found in arterial samples in children may rep-resent the lower
limit of a variable quantity whichis determined by factors which
regulate both the
PH.40 Pft pHI
amount of right to left shunt and the venous oxy-gen level.
Saturation levels determined by theear oximeter are usually higher
because they aremeasured under conditions that are less
disturbingto the patient than are arterial punctures.The finding of
a low alkaline reserve of the
plasma in patients with cyanotic congenital heartdisease has
been reported previously by Talbottet al. (1) and by Suarez,
Chiodi, Fasciolo, andTaquini (3). It has also been suggested by
thelow CO2 contents of arterial blood found in Tal-bott's summary
of the literature (1), and in theserum of arterial blood as
reported by Bing et al.(2).Talbott et al. (1) first described the
analogy be-
tween the tissue anoxia of patients with cyanoticcongenital
heart disease and that of persons livingunder the low oxygen
pressure of high altitudes.He attributed the low alkaline reserve
of the bloodin these patients to the effects of chronic
hyperven-
7.40 pH, pHs 7.40 PHs
FIG. 3. ARTERIAL (HCO,) ., PCO2 AND pH. OF THE BLOOD OF PATIENTS
WITH CYANOTIC CONGENITALHEART DISEASE, PLOTTED ON TRIAXIAL
COORDINATES
The shaded areas represent the range of normal variation for the
various age groups as determined by+ 2 standard deviations from the
mean value of each group.
843
-
MINERVA MORSE AND DONALD E. CASSELS
tilation, but he also recognized that some otherfactors caused
the acidosis which was observed inthe patient he had studied so
extensively and inseveral other cases reported in the
literature.Bing et al. (2) found that the minute volume
ofrespiration was increased above the normal in 29out of 30 cases
of cyanotic congenital heart dis-ease, but the arterial pCO2 and
the alkaline re-serve were reduced proportionately and the
ar-terial pH. remained within normal limits.Suarez, Chiodi,
Fasciolo, and Taquini (3) foundhyperventilation to be
characteristic of the six pa-tients with this disease which they
studied andarterial pH. in the normal range or slightly low.
Bing et al. (2) emphasized the difference inconditions under
which tissue anoxia is producedin patients with congenital heart
disease and inresidents at high altitudes. In the latter a
lowalveolar oxygen pressure produces the low arterialPO2 and
saturation. Hyperventilation is bene-ficial in that it raises the
alveolar PO2. In patientswith cyanotic congenital heart disease on
the otherhand low arterial PO2 and saturation levels arecaused by
venous admixture through abnormalchannels. Beneficial effects of
hyperventilationare questionable in such patients since the
bloodthat passes through the lungs is exposed to a highoxygen
tension and is well oxygenated, while the'blood shunted from the
right to the left side ofthe heart does not pass through the
lungs.
Presumably hyperventilation rises in response toan anoxic
stimulus both in patients with cyanoticcongenital heart disease and
in residents at high al-titude. Dill, Talbott and Consolazio (13)
showedthat an essential process in acclimatization to highaltitude
consists first of hyperventilation to increasealveolar oxygen
pressure, followed later by a re-duction of the alkaline reserve of
the plasma bykidney action to the point where the normal
ratiobetween the pCO2 and the serum bicarbonate isreached. Both
Dill, Talbott and Consolazio (13)and Hurtado and Aste-Salazar (14)
found thatthe arterial blood serum of permanent residentsat high
altitude is characterized by a lowering ofthe pCO2 proportional to
that of the alkaline re-serve, with a normal or slightly low pH8,
in con-trast to the elevated pH. of the arterial blood oftemporary
residents at high altitude. Patients
with cyanotic congenital heart disease resembleresidents at high
altitude in that they are ac-climatized to their state of anoxia.
Our resultsshow that for a given degree of arterial unsatura-tion
the blood of patients with cyanotic congenitalheart disease shows
less of a depression of alkalinereserve than that of residents at
high altitude.Since for equal degrees of alveolar hyperventila-tion
the arterial pCO2 must remain higher in theblood of patients with
cyanotic congenital heartdisease because of the venous admixture it
con-tains, there is need for less decrease in the alkalinereserve
of the blood in these patients in order tomaintain a normal
arterial pHi.The case of cyanotic congenital heart disease
studied by Talbott et al. (1) was unusual becauseof the low
arterial pH. which was observed. Thepresent report shows 32 per
cent of pH8 valuesbelow the lower limit of normal. The great
ma-jority of pH8 values below 7.30 were found insamples showing
less than 60 per cent saturationand are therefore associated with
large venous-arterial shunts. In such cases of severe hypoxia alow
pH. offers compensation by raising arterialoxygen tension, hence
mean capillary oxygenpressure, through the Bohr effect on the
oxygendissociation curve.The low pH. of the arterial-blood and the
lack
of balance in the common electrolytes of the serumin cases of
severe hypoxia led Talbott to suggestthe presence of increased
concentrations of organicacids in the blood. Since tissue
metabolism ap-parently proceeds at relatively low levels of oxy-gen
tension, it is conceivable that enzyme reactionsinvolved in muscle
metabolism operate at a moreanaerobic level, with production of
lactic acid inlarger quantities than normal. Our results agreewith
those of Hallock (15), Bing et al. (2), andHavel and Watkins (5) in
showing that in theresting state the lactic acid concentration in
theblood of cyanotic patients with congenital heartdisease is not
significantly higher than in thenormal person, and that the
slightly elevated lacticacid levels that are occasionally found are
notgreat enough to explain the deficiencies in theelectrolyte
balance.
It is important to note also that although Binget al. (2) found
that the basal oxygen consump-
844
-
BLOOD GASES IN CYANOTIC CONGENITAL HEART DISEASE
TABLE IV
Serum electrolyte concentrations in the arterial blood of
patients with cyanotic congenital heart disease
Oxygen (HCOs)s+satura- HbOi (Pro- (C1)a+(Pro-
Age tion capacity (HCOs), (Cl)5 teinate)s teinate)5 (Lactate),
(Sodium).yr. Subject per cent Vol. % mEq./L. mEq./L. mEq./L.
mEq./L. mEq./L. mEq.IL. pHs
Group I. Normal values for (HCOs). + (Cl). + (Proteinate).3 W.
B. 63.4 23.2 18.8 110.0 16.6 145.4 1.9 7.4146 J. T. 83.6 23.8 20.0
106.3 18.1 144.4 2.9 7.3777 V. S. 61.8 26.6 19.8 105.6 19.6 145.0
1.2 7.234
10 J. S. 72.1 27.3 20.3 105.1 20.4 145.8 1.0 7.39816 B. N. 90.1
27.9 20.2 106.3 18.0 144.5 1.8 7.39416 M. C. 81.0 26.2 18.7 106.6
17.5 142.8 1.0 7.351
Adult R. G. 79.7 25.7 21.2 108.2 15.6 145.0 0.6 7.408Mean 76.0
25.8 19.9 106.9 18.0 144.7 1.5 7.382
Group II. Low values for (HCO,). + (Cl). + (Proteinate),3 N. H.
84.1 26.0 17.6 99.8 17.8 135.2 1.5 7.4324 J. M. 54.3 31.4 19.7
100.6 15.0 135.3 1.2 133.6 7.2325 A. F. 70.4 27.8 20.7 103.2 14.0
137.9 1.6 7.3926 R. B. 40.5 28.6 16.1 104.2 18.0 138.3 2.9 7.2446
R. B. 39.2 26.5 16.9 103.2 17.8 137.9 2.6 7.3007 J. M. 40.6 31.1
15.3 104.2 16.6 136.1 1.7 146.3 7.2447 W. G. 70.6 27.8 19.8 101.7
18.5 140.0 1.6 7.3338 D. M. 82.8 22.5 19.2 104.1 17.3 140.6 1.8
7.429
10 S. D. 66.1 29.4 18.1 98.3 19.5 135.9 2.1 139.8 7.32511 S. D.
77.1 35.7 19.3 101.5 16.4 137.2 1.7 7.372
Adult D. B. 82.4 35.7 20.2 103.3 16.3 139.8 1.1 7.352Mean 64.4
29.3 18.4 102.2 17.0 137.7 1.8 7.332
tion was usually below the normal mean in thesepatients, that
finding has not been corroborated inour laboratory or by other
investigators such asBurchell, Taylor, Knutson, and Wood
(4),Suarez, Chiodi, Fasciolo, and Taquini (3) andErnsting and
Shephard (6). We must concludethat metabolic requirements for the
resting stateare met by adequate oxygen consumption in pa-tients
with marked arterial unsaturation. Atpresent it is not known
whether this is made pos-sible by modifications in the complex of
enzymaticprocesses involved in tissue metabolism andwhether the
production of organic acids other thanlactic acid are increased
under these conditions.The problem requires further study. The
pos-sibility of alterations in renal excretion also mustbe studied
in this connection.
SUMMARY
The blood gases and acid-base balance of theblood were
determined in arterial samples from60 patients with cyanotic
congenital heart diseasewho varied in age from 1 to 36 years. The
re-sults may be summarized as follows:
Arterial saturation varied from 21 to 93 percent. Saturations
below 50 per cent were foundonly in children under 8 years of
age.
In 80 per cent of the cases HbO2 capacities weremore than 2 vol.
per cent higher than the normalmean for the appropriate age. Of
those withnormal or below normal HbO2 capacities, halfwere cases
with arterial saturation between 87and 92 per cent, and the
majority of the remainderwere infants in whom a nutritional iron
deficiencywas suspected. Very high HbO2 capacities, over32 vol. per
cent, were usually found only in olderchildren and in adults.By
means of high HbO2 capacities the oxygen
content of the arterial blood was maintained withinthe normal
range in all but 15 per cent of thecases.
The alkaline reserve of the plasma tended to bereduced, for
approximately two-thirds of the ob-served values were below tle
lower limit of nor-mal. Arterial pCO2 was below the normal rangein
only one-third of the cases. As a result, valuesfor arterial pH.
were below the lower limit ofnormal in approximately one-third of
the cases.A rough relationship was fQund to exist be-
845
-
MINERVA MORSE AND DONALD E. CASSELS
tween the degree of arterial unsaturation and theextent of the
deviations of the HbO2 capacity,alkaline reserve and arterial pH.
from the normalmean.
Deviations of the acid-base characteristics of theserum from the
normal were found to be due inmost cases either to fixed acid
excess or to a com-bination of fixed acid excess and CO2
deficit.
Calculation of a partial electrolyte balanceshowed that in some
cases the reduced bicarbon-ate concentration of the serum was
balanced by arise in serum chloride concentration. In othercases
there was no evidence of replacement ofserum bicarbonate by
chloride, nor by increasedlactate concentration. The question of a
cor-responding reduction of total fixed base or anincrease in other
organic acids has not been in-vestigated sufficiently.The
determination of arterial blood gases in
samples drawn post-operatively, after pulmonaryblood flow had
been increased by aortic-pulmonaryartery anastomosis or pulmonary
valvulotomy,showed a marked rise in the alkaline reserve andthe
arterial pH. of the blood, in addition to thewell-known increase in
arterial saturation andreduction of HbO2 capacity.
ACKNOWLEDGMENTS
The authors acknowledge with gratitude the technicalassistance
of Lottie Walaszek Pietrowski, June BreidijanDenemark, Melba
Holder, Florence Numajiri Field, AxelSwanson and Edna
O'Connell.
REFERENCES1. Talbott, J. H., Coombs, F. S., Castleman, B.,
Chamber-
lain, F. L., Consolazio,.W. V., and White, P. D.,A record case
of the Tetralogy of Fallot, with com-ments on metabolic and
pathologic studies. Am.Heart J., 1941, 22, 754.
2. Bing, R. J., Vandam, L. D., Handelsman, J. C.,Campbell, J.
A., Spencer, R., and Griswold, H. E.,Physiological studies in
congenital heart disease.VI. Adaptations to anoxia in congenital
heart dis-
ease with cyanosis. Bull. Johns Hopkins Hosp.,1948, 83, 439.
3. Suarez, J. R. E., Chiodi, H., Fasciolo, J. C., andTaquini, A.
C., Respiration and circulation inmorbus coeruleus. Acta
cardiologica, 1949, 4, 439.
4. Burchell, H. B., Taylor, B. E., Knutson, J. R. B., andWood,
E. H., Circulatory adjustments to the hy-poxemia of congenital
heart disease of the cyanotictype. Circulation, 1950, 1, 404.
5. Havel, R. J., and Watkins, E., Jr., The metabolism oflactate
and pyruvate in children with congenitalheart disease. Circulation,
1950, 2, 536.
6. Ernsting, J., and Shephard, R. J., Respiratory adap-tations
in congenital heart disease. J. Physiol.,1951, 112, 332.
7. Cassels, D. E., and Morse, M., Arterial blood gasesand
acid-base balance in normal children. J. Clin.Invest., 1953, 32,
824.
8. Bing, R. J., Vandam, L. D., and Gray, F. D.,
Jr.,Physiological studies in congenital heart disease.II. Results
of preoperative studies in patients withTetralogy of Fallot. Bull.
Johns Hopkins Hosp.,1947, 80, 121.
9. Hastings, A. B., and Steinhaus, A. H., A new chartfor the
interpretation of acid-base changes and itsapplication to exercise.
Am. J. Physiol., 1931, 96,538.
10. Shock, N. W., and Hastings, A. B., Studies of acid-base
balance of the blood. IV. Characterizationand interpretation of
displacement of the acid-basebalance. J. Biol. Chem., 1935, 112,
239.
11. Dill, D. B., Christensen, E. H., and Edwards, H. T.,Gas
equilibria in the lungs at high altitudes. Am.J. Physiol., 1936,
115, 530.
12. Talbott, J. H., and Dill, D. B., Clinical observations
athigh altitude. Observations on six healthy personsliving at
17,500 feet and a report of one case ofchronic mountain sickness.
Am. J. M. Sc., 1936,192, 626.
13. Dill, D. B., Talbott, J. H., and Consolazio, W. V.,Blood as
a physicochemical system. XII. Man athigh altitudes. J. Biol.
Chem., 1937, 118, 649.
14. Hurtado, A., and Aste-Salazar, H., Arterial bloodgases and
acid-base balance at sea level and at highaltitudes. J. Appl.
Physiol., 1948, 1, 304.
15. Hallock, P., Lactic acid production during rest andafter
exercise in subjects with various types ofheart disease with
special reference to congenitalheart disease. J. Clin. Invest.,
1939, 18, 385.
846