The acid-base and biochemical characteristics of intrapartum fetal asphyxia J.
A.
S. R.
LOW,
M.D.
PANCHAM,
M.D.
D.
WORTHINGTON,
R.
W.
Kingston,
BOSTON, Ontario,
M.D. M.D.
Canada
The maternal and fetal acid-base, lactate, and pyruvate characteristics during the course of labor and at delivery were studied in 124 patients delivered of an infant with evidence of metabolic acidosis at delivery. This metabolic acidosis is principally caused by hyperlactatemia resulting from the tissue oxygen debt accompanying fetal asphyxia. Hypoxemia was one mechanism contributing to this fetal asphyxia and tissue oxygen debt. This evidence of fetal asphyxia developed during the last half and principally during the last two hours of the intrapartum period. Acid-base assessment of fetal blood with identification of a metabolic
acidosis
will
provide
an accurate
objective
diagnosis
T H E 0 B J E C T IV E of the present study was to examine the biochemical characteristics, the pattern of development, and the mechanisms relevant to the occurrence of intrapartum fetal asphyxia. The acidbase and biochemical characteristics of 140 normal obstetric patients with a normal fetus have been reported1 and serve as the “normal” group in the present review. The asphyxia group included 124 patients delivered of an infant with evidence of a metabolic acidosis at delivery. The criterion used was an umbilical artery buffer base < 36.1 mEq. per liter, which represents two standard deviations below the mean in the normal group.
asphyxia.
Results
Fetal acid-base characteristics. The
acid-base characteristics in fetal capillary blood during labor and in the umbilical vein and arterial blood at delivery in the asphyxia group are compared to the normal group in Table I. The development of metabolic acidosis in the asphyxia group is identified by the fetal capillary blood estimations during labor. The fetal capillary buffer base in the asphyxia group at midlabor, 41.9 mEq. per liter, is essentially the same as the fetal capillary buffer base one hour prior to delivery in the normal group. The capillary blood buffer base is significantly lower in the asphyxia group two hours prior to delivery, 38.9 mEq. per liter (paired t value, 3.01)) and one hour prior to delivery, 39.2 mEq. per liter (paired t value, 3.24)) with a further decrease at delivery to 36.6 mEq. per liter. This terminal capillary blood buffer base is between the umbilical vein and the umbilical artery buffer base. The changes in buffer base in the asphyxia group during labor and at delivery are associated with parallel changes in pH. The pH is significantly
Department of Obstetrics and and the Department of Paediatrics,
Queen’s University. Presented at the Thirtieth Annual Meeting of the Society of Obstetricians and Gynaecologists Canada, Murray Bay, Quebec, Canada, June 20-23, 1974.
fetal
lactate, and pyruvate characteristics at delivery. Measurements of pH, oxygen tension, carbon dioxide tension, buffer base, and lactate and pyruvate concentrations were carried out as previously described.l
Methods The observations made include maternal venous blood acid-base, lactate, and pyruvate characteristics during labor and at delivery, fetal acid-base characteristics during the last half of labor, and acid-base, From the Gynaecology
of intrapartum
of
Reprint requests: Dr. J. A. Low, Department of Obstetrics and Gynaecology, Queen’s University, Kingston, Ontario, Canada.
446
Volume Numhrr
121 4
Acid
50
1
base
and
UMBILICAL
biochemistry
of
intrapartum
asphyxia
447
ARTERY
Buffer
Base
50
60
-
Lactate
25.
01 IO
20
30
40
70
80
90
100
LACTATE
Fig. 1. Relationship between umbilical artery buffer base and umbilical tration in the combined normal and asphyxia groups.
lower two hours prior to delivery, 7.225 (paired t value, 3.77), and one hour prior to delivery, 7.221 (paired t value, 4.16)) with a further decrease at delivery to 7.176, which is between the umbilical vein and artery pH. Fetal lactate and pyruvate characteristics. The lactate, pyruvate, and lactate-pyruvate ratio at delivery in the asphyxia group are compared to those in the normal group in Table II. The lactate concentration in the asphyxia group in the umbilical vein, 37.4 mg. per cent (paired t value, 8.63), and in the umbilical artery, 46.4 mg. per cent (paired t value, 8.95)) is significantly higher than in the normal group. The pyruvate concentration in the asphyxia group in the umbilical vein, 1.60 mg. per cent (paired t value, 6.10)) and in the umbilical artery, 1.76 mg. per cent (paired t value, 6.36)) is significantly higher than in the normal group. The increase in lactate exceeds the increase in pyruvate concentration; thus, the lactate-pyruvate ratio in the asphyxia group in the umbilical vein, 22.1 (paired t value, 7.65)) and in the umbilical artery, 26.7 (paired t value, 7.92)) is significantly higher than in the normal group. The relationship between umbilical artery buffer base and lactate concentration and umbilical artery buffer base and lactate-pyruvate ratio in the combined normal group and asphyxia group is presented in Figs. 1 and 2. There is a highly significant correlation between decreasing buffer base and in-
artery lactate concen-
45
UMBILICAL
40 A . w” E : cl al
.
* .a*
*I . : :r. .‘:.: ..:...: . i ’
35.
30.
” IL IL
Base
Lactate
- Pyruvate
Ratio
. . . .;
.
A 0:
. *
ARTERY
Buffer
*
:
. * .
25
.
/
15 1 lOi
IO
20 LACTATE
30
40 - PYRUVATE
50
60
70
80
RATIO
Fig. 2. Relationship between umbilical artery buffer base and umbilical artery lactate-pyruvate ratio in the combined normal and asphyxia groups. creasing lactate concentration (coefficient of correlation, 0.84; R, 0.708) (Fig. 1) and between decreasing buffer base and increasing lactate-pyruvate ratio (coefficient of correlation, 0.78; R, 0.603) (Fig. 2). Fetal blood-gas characteristics. The oxygen tension and saturation in the asphyxia group are compared to the normal group in Table I. The capillary oxygen tension in the asphyxia group is lower, although not significantly so, at midlabor, 16.9 mm.
448
Low et al.
Table I. The normal group
pH,
buffer
base, carbon
dioxide
tension,
and
oxygen
tension
--+*jy;-
in fetal
capillary
blood
prior
PH Mean Normal1
Midlabor 120 min. prior to delivery 60 min. prior to delivery O-15 min. prior to delivery Umbilical vein Umbilical artery
7.313 7.279 7.340 7.270
S.D.
Mean Asphyxia 1
S.D.
0.05 0.07 0.05 0.05
7.294 7.225 7.221 7.176 7.223 7.109
0.04 0.09 0.10 0.08 0.11 0.12
ratio group
in umbilical
Table II. The lactate, pyruvate, and lactate-pyruvate in the fetal asphyxia group compared to the normal Lactate
Vein Artery
Table III. at delivery
1
Asphyxia S.D.
19.4 22.7
2.0 3.7 2.0 2.5
vein and artery
blood
2.9 4.:; 4.1 4.0 4.2 4.1
at delivery
Pvruvate
Normal Mean
42.2 42.0 42.8 41.1
41.9 38.9 39.2 36.6 37.0 32.4
Mean
8.0 9.6
/
37.4 46.4
Normal S.D.
19.1 20.7
Mean
/
Asphyxia S.D.
1.19 1.34
0.35 0.35
Mean
)
1.60 1.76
Lactate-pyruvate S.D.
Normal
0.56 0.47
The pH, buffer base, and lactate concentration in maternal venous in the fetal asphyxia group compared to corresponding observations
ratio 1
Asphyxia
16.0 17.0
22.1 26.7
blood during in the normal
labor and group -
Buffer
PH Normal Mean
Onset of labor Midlabor Second stage Delivery
7.408 7.433 7.423 7.377
Normal
Asphyxia
( S.D.
0.03 0.05 0.06 0.05
Mean 7.391 7.399 7.401 7.373
( S.D.
Mean
1 S.D.
42.2 43.3 42.2 41.3
1.7 1.6 1.7 1.7
0.02 0.04 0.04 0.06
Hg (paired t value, 2.28)) and two hours prior to delivery, 17.0 mm. Hg (paired t value, 1.23)) but is significantly lower one hour prior to delivery, 15.5 mm. Hg (paired t value, 3.40). The oxygen tension at delivery, 14.0 mm. Hg, is between the umbilical vein and the umbilical artery oxygen tension. The asphyxia group umbilical vein oxygen tension, 25.8 mm. Hg (paired t value, 2. lo), and umbilical artery oxygen tension, 12.9 mm. Hg (paired t value, 2.95), are slightly but significantly lower than the corresponding observations in the normal group. The calculated oxygen saturation emphasizes the relevance of these small decreases in oxygen tension caused by the shift of the oxygen dissociation curve as a result of the low pH in the asphyxia group. The oxygen saturation and content during the last two hours of labor are approximately half that in the normal group.
base
Asphyxia Mean 1 S.D. 41.4 1.9 41.0 2.3 41.0 2.3 40.1 2.2
Lactate Normal Mean
9.8 10.8 16.7 20.7
Asphyxia
1 S.D.
2.7 3.7 8.5 9.5
1
Mean 11.6 12.8 15.5 20.0
S.D.
4.1 5.3 5.6 9.1
The CO, tension in the asphyxia group is compared to the normal group in Table I. The capillary CO2 tension in the asphyxia group at midlabor, 47.0 mm. Hg, is essentially the same as the CO, tension one hour prior to delivery in the normal group. The CO, tension in the asphyxia group is higher two hours prior to delivery, 55.0 mm. Hg (paired t value, 2.60), and one hour prior to delivery, 51.5 mm. Hg increase at (paired t value, 2.13), with a further delivery to 58.0 mm. Hg, which is between the umbilical vein and umbilical artery Pco,. The asphyxia group umbilical vein CO, tension, 45.6 mm. Hg (paired t value, 4.73), and umbilical artery CO, tension, 60.3 mm. Hg (paired t value, 6.26)) are significantly higher than the normal group. The relationship between the umbilical artery lactate-pyruvate ratio and CO, tension and the umbilical artery lactate-pyruvate ratio and oxygen
to
Volume 121 Number
delivery
Acid
base
and
biochemistry
of intrapartum
asphyxia
449
4
and in umbilical
vein
and artery
blood
at delivery
1
45.0 51.0 39.6 50.7
group compared
PO?
PC02 Normal Mean
in the asphyxia
Normal
Asphyxia S.D.
Mean
7.0 7.8 5.5 6.8
47.0 55.0 51.5 58.0 45.6 60.3
1
Mean
S.D. 6.2 11.0 8.9 10.3 13.7 15.9
1
19.8 16.6 27.7 14.9
O9 saturation (%I
Asphyxia S.D.
Mean
3.4 4.3 6.4 4.6
16.9 17.0 15.5 14.0 25.8 12.9
to the
(
S.D.
Normal
3.7 9.1 4.3 4.2 7.7 6.1
1 Asphyxia 32 26 22 15 50 10
42 30 67 24
loo.
90.
UMLIILICAL
ARTERY
Loctote Pyruvote COP Tension
Ratio
40. 30.
201
IO
20
30
40
LACTATE
Fig. 3. Relationship between tension in the asphyxia group.
30-
umbilical
UMBILICAL Lactote
:, v, 5 + 6
60
artery
70
80
lactate-pyruvate
ratio
too
and
umbilical
FETAL
ARTERY
- Pyruvote
90
RATIO
artery
CO:
ASPHYXIA
Ratio
0, Tension
25I" E
50
- PYRUVATE
FETAL
ASPHYXIA
I
20. TISSUE
OXYGEN
DEBT
15.
.
IO-
HYPERLACTATEMIA
WITH
INCREASED
L’P
RATIO
5I IO
20
30 LACTATE
Fig. 4. pyruvate asphyxia
Relationship ratio and group.
\ 40
METABOLIC 50
- PYRUVATE
between umbilical umbilical artery oxygen
60
70
ACIDOSIS
WITH
DECREASED
BUFFER
BASE
80 1
RATIO
artery lactatetension in the
DECREASE
Fig. 5. Biochemical phyxia.
and
OF
acid-base
pH
response
to
fetal
as-
450
February Am. J. Obstet.
Low et. al.
BUFFER
PH
BASE
LI
7 150.
I 1
7.100.
CO, TENSION
1
30.
0,
TENSION
I
40.
d
20. C-Y
25
35-
15, 1975 Gynecol.
i I I
15-
x
I Y
7.050
, MID
. 120
Fig. 6. The pattern normal and asphyxia
60
20 15 1 DELIVERY
, MID
of acid-base groups.
I20
60
changes
30 * I5 1 DELIVERY
MID
120
60
during
the
last
half
tension in the asphyxia group is presented in Fig-s. 3 and 4. There is a significant relationship between increasing lactate-pyruvate ratio and increasing CO, tension (coefficient of correlation, 0.72; R, 0.523) (Fig. 3) and decreasing oxygen tension (coefficient of correlation, 0.44; R, 0.198) (Fig. 4). Maternal acid-base characteristics. Representative acid-base and lactate observations in maternal venous blood of the asphyxia group are compared to those of the normal group in Table III. The pattern for pH, buffer base, and lactate concentration throughout labor and at delivery in the asphyxia group closely paralleh the corresponding observations in the normal group.
Comment The essential interrelationships in respect to fetal asphyxia are outlined in Fig. 5. Fetal asphyxia results in tissue oxygen debt. Laboratory identification and assessment of tissue oxygen debt is based upon the resultant hyperlactatemia which leads to metabolic acidosis, decreased buffer base, and, in turn, a decrease of pH. The criterion for the asphyxia study group was metabolic acidosis at delivery defined by an umbilical artery buffer base less than 36.1 mEq. per liter, which is two standard deviations below the mean in the normal group. The importance of hyperlactatemia in respect to
IO 15 1 DELIVERY
of labor
MID
and
120
60
IS 1 DELIVERY
at delivery
in the
this metabolic acidosis is indicated by the high degree of correlation in the combined normal and asphyxia groups between decreasing buffer base and increasing lactate concentration. Thus, although other fixed acids may be responsible for a metabolic acidosis, lactic acid was the principal fixed acid in these infants. Hyperlactatemia may be caused by one of two mechanisms. The first mechanism, which is essentially innocuous, results from an increase of pyruvate concentration. There is a small but significant increase of pyruvate concentration in the asphyxia group which contributes to a small component of the hyperlactatemia. The second mechanism is caused by a tissue oxygen debt which results in a rise of lactate concentration without a corresponding rise of pyruvate and leads to a corresponding increase of the lactate-pyruvate ratio. The importance of the tissue oxygen debt in respect to the hyperlactatemia and metabolic acidosis is indicated by the high degree of correlation in the combined normal and asphyxia group between decreasing buffer base and increasing lactate-pyruvate ratio. The pattern of development of fetal asphyxia and metabolic acidosis in the asphyxia group is outlined in Fig. 6. There is no evidence of fetal asphyxia in this study group at midlabor. The developing fetal asphyxia during the last half of labor is identi-
Volume 121 Number4
Acid
fied by the progressive decrease of pH and buffer base measured during the last two hours of labor and at delivery. The factors leading to tissue oxygen debt are frequently complex and often difficult to define accurately.” The significance in this asphyxia group of deficient maternal-fetal blood-gas exchange leading to hypoxemia and hypercapnea is indicated by the lower oxygen tension and higher CO2 tension in the asphyxia group in relation to the normal group and the significant correlation at delivery between the increasing lactate-pyruvate ratio and the decreasing oxygen tension and increasing CO, tension in the asphyxia group. The extent of the hypoxemia is more accurately indicated by the oxygen saturation. The small decrease of oxygen tension in the asphyxia group caused by the shift of the oxygen dissociation curve results in a marked decrease of oxygen saturation and content. The oxygen saturation in the asphyxia group is just 50 per cent of that in the normal group during the last 2 hours of labor.
Note
to Authors:
Change
in Reference
base
and
biochemistry
of
intrapartum
asphyxia
451
Although maternal metabolic acidosis may occur in individual instances, it was not a significant factor in the fetal metabolic acidosis in this asphyxia group. The maternal venous blood acid-base and lactate characteristics in the asphyxia group were similar to the maternal observations in the normal group. The accurate diagnosis of fetal asphyxia with tissue oxygen debt can be provided by the acid-base assessment of fetal blood with identification of the presence of a fetal metabolic acidosis. The observation is usefully complemented by measurement of a parallel hyperlactatemia and increased lactate-pyruvate ratio. The availability of such laboratory documentation of fetal asphyxia is essential to any clinical investigation of fetal asphyxia and the optimal management of individual clinical problems. REFERENCES
1.
2.
Low, J. A., Pancham, S. R., Worthington, Boston,, R. W.: AM. J. OBSTET. GYNECOL. 1974. Huckahee, W. E.: Am. J. Cardiol. 12: 663,
Style
The Editors and Publisher have agreed to add the article title to references in the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. References will now conform to the style of the Cumulated Index Medicus, viz., name of author, title of article, name of periodical, volume, page, and year. Authors are always encouraged to limit references to sixteen for the following JOURNAL sections: Obstetrics, Gynecology, and Fetus, Placenta, and Newborn.
D., and 120: 862, 1963.