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Spinal anesthesia for cesarean section
Spinal anesthesia for cesarean section Physiological and biochemical observations
VINCENT STENGER, M.D. THORKILD .A.. ~~DERSE~~'
~1.D.
CONSTANTE DE PADUA, M.D. DONALD EITZMAN, M.D. IRA GESSNER, M.D. HARRY PRYSTOWSKY, M.D. Gainesville, Florida
THE PLAcENTA presents itself as a tissue barrier that separates the maternal and fetal bloods. All materials that move from one circulation to the other must cross that barrier. This movement may be accomplished in different ways. The respiratory gases. cross by diffusion; they move from the plasma of higher concentration to the plasma with the lower. The degree to which this tissue barrier of the placenta restricts or promotes the movement of materials to the fetal circulation must affect their availability to the fetus and the degree to which the barrier limits or promotes movement from the fetal blood must be reflected in the composition of the fetal internal environment. Accordingly, the interest of the physiologist and the ciinician centers about such questions as the following: What is the normal limitation placed by the
tissue barrier upon the free movement of oxygen and carbon dioxide from one circulation to the other; what are the consequences and signs of an increase in that limitation; and, finally, what measures may be taken when the limitation exceeds a normal range to improve the position of the fetus? The data presented here on spinal anesthesia for cesarean section were obtained as a part of a wider investigation of the oxygen supply to the human fetus. As the first step in this program we estimated the arteriovenous oxygen difference across the human pregnant uterus at selected stages in gestation.1 Next we examined the characteristics of fetal and maternal bloods in regard to the blood gases, 2 total osmotic pressure, sodium, and potassium concentrations.' During the course of our study we soon became aware of the profound changes which occurred when functional sympathetic denervation was carried out at the time of elective cesarean section and realized that such circumstances provided us with an opportunity to evaluate the effect of severe maternal hypotension on maternal-fetal relationships and an opportunity to gain insight into mechanisms, maternal and fetal, that exist when gestation is subjected to acute stress. Although the number of patients evaluated is few, the data are complete and reproducible,
From the Departments of Obstetrics and Gynecology, Anesthesiology, and Pediatrics, University of Florida College of Medicine.
This research was supported in part by United States Public Health Service Grants HD-00546-02, H-7129. and 2A 5273. . . Presented by invitation at the Twentysixth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Bal Harbour, Florida, fan. 26-29, 1964.
51
52
Stenger et al.
and certain points of interest emerge from them with sufficient clarity that we do not hesitate to present them at this time. Material and methods
Our observations were made at the University of Florida Teaching Hospital. The 5 patients studied were delivered by cesarean section; 4 were normotensive and 1 had essential hypertension. All were operated upon between the thirty-eighth and fortieth weeks of gestation. Each individual was prepared for study in the following manner: in the supine position and under local anesthesia (Xylocaine 1 per cent) Cournand needles were placed in the radial arteries. A catheter was inserted in an antecubital vein and threaded up to the level of the subclavian vein. Electrocardiographic (EKG) leads were placed. Connection was then made between one artery, the vein, and the EKG equipment with a four channel recorder. The other radial artery was prepared so that it could be utilized for apparatus designed to measure cardiac output in a repetitive manner and at short intervals, i.e., dye dilution technique. 4 Each patient served as her own control. Our procedure was as follows: a continuous recording of intra-arterial blood pressure, EKG, venous pressure, pulse rate, a determination of cardiac output, and collection of 20 mi. of maternal arterial blood in a heparinized and oiled syringe were first obtainedthe so-called "control" period. The single dose technique of spinal anesthesia was then administered. The patient was placed in the left lateral decubitus position while receiving an infusion of 5 per cent dextrose in water. The operating table was adjusted so that the vertebral column was parallel to the floor. A diminution of the lumbar spinal curvature was then effected by having the patient held in complete flexion by an assistant. The lower back was then prepared \Vith tincture of zephiran and draped in sterile fashion. With a stock solution of 1 per cent procaine and a standard No. 26 gauge needle on a 2 mi. syringe a skin wheal was raised in the midline over
Am.
September l, 1964 J Obst. & Gynec.
the interspace between lumber 3 and lumbar 4. Using a No. 22 gauge needle and the same syringe, the interspace was infiltrated with the 1 per cent procaine to the depth of the ligamentum flavum. A midline intrathecal puncture was then made with a No. 26 gauge 3 inch spinal needle with the bevel directed downward. The previously prepared mixture of 0.8 ml. (8 mg.) of pontocaine and 0.8 mi. ( 80 mg.) of 10 per cent dextrose was administered in a steady stream with constant pressure. The spinal needle was then removed and the patient immediately placed in the supine position with a folded pillow under her head. Deep Trendelenburg position was not employed. In one individual 50 mg. of ephedrine was given intramuscularly prior to the anesthesia--mention will be made of this case later in the presentation. Immediately thereafter a second series of recordings, cardiac output determination, and maternal arterial blood collection was carried out. Thereafter, the recording of venous pressure, intra-arterial blood pressure, EKG, and pulse rate were continuous; cardiac output evaluations were likewise repeated. Through a lower midline incision the peritoneal cavity was entered. The uterus was then gently rotated to one side. Another cardiac output was determined. A No. 20 gauge needle attached to a heparinized and oiled syringe was then inserted into one of the large tributaries of the uterine vein which lie lateral to the uterus. Twenty milliliters of blood were then simultaneously collected from the uterine vein and the maternal artery. The uterus was then incised and the fetus delivered. After clamping the umbilical cord, the umbilical vein was sampled immediately at the operating table. In this presentation we shall only be concerned with specimens simultaneously collected from the maternal artery and uterine vein, and the umbilical vein at the moment of delivery. After each collection of blood, the syringe was capped and immediately placed into a beaker containing ice and water. Analyses were performed immediately after the ter-
Anesthesia for cesarean section
Volume 90 Number 1
ruination of the experiment, i.e., within 30 minutes. The oxygen and carbon dioxide contents of each sample were determined in duplicate on 0.5 ml. specimens by the method of Van S!yke and Neill. 5 The oxygen capacity was measured by the same technique as described in a previous paper. 6 The percentage saturation of the blood was calculated by dividing oxygen capacity into oxygen content and multiplying by 100, i.e., (oxygen content -;oxygen capacity) x (100) =percentage saturation. The saturation was then referred to an appropriate oxygen dissociation curve 7 • 8 9 • ; in this manner the partial pressure of oxygen ( p0 2 ) in each sampie was estimated. Another aliquot of the blood sample was transferred to a centrifuge tube under oil, and cells and plasma were separated by centrifugation at 3,000 r.p.m. for 45 minutes. The carbon dioxide content of each plasma sample drawn from the centrifuge tube and transferred to the Van Slyke pipette by means of an oiled syringe was determined in duplicate by the manometric method of Van Slyke and Neill 5 on 0.5 ml. samples. The pH of each specimen was determined by means of a Beckman expanded scale meter, Model 76, which had been set at 37° C. and previously standardized with a buffer of known pH. (The reading error was ± 0.01 units.) Knowing the total carbon dioxide content and pH of each plasma sample, the physically dissolved carbon dioxide was calculated from the Henderson-Hasselbalch equation: pH
= 6 · 10 + log
total C02"·dissolved C02 dissolved COz
The carbon dioxide tension in millimeters of mercury was then calculated from the dissolved carbon dioxide by means of the Bunsen coefficient, i.e., dissolved C0 2 /0.0301) = pC0 2 , where 0.0301 is the quantity of carbon dioxide in rnillimols, dissolved in 1 liter of plasma at standard temperature and pressure per rnm. Hg of carbon dioxide tension, and where the concentration of dissolved carbon dioxide is also expressed in rnillimols per liter. Another part of the plasma sample was
SPINAL ANESTHESIA FOR
CESAREAN SECTION-
THE INTRAARTERIAL BLOOD PRESSURE
! Re.stin9
i60~ 150 140
~ 130~
!
120
~
"110
~
:::
Q:"
".!!
100 90
Q
"'
80
C;
70
~
60
Q
50
·~
.::"
.!: 4n
~~~
I
i
"Spinal Floor"
l I
r l I
lj ll II
l
II
20
II I
10 0 Potient
11.F.
J.J.
RESPONSE
Control BP
r
I
53
s.s.
Ul.
I
l
I II
j
I
I L!J I F. H.
Fig. 1.
used for determination of freezing point. The measurement \vas made \vith a Fiske osmom= eter on 2 ml. specimens. The samples, previously cooled to 4° C., were transferred directly from the syringes in which they were stored by means of a long needle to the bottom of a test tube. Treated in this manner the plasma loses no more than 1 mOs. per kilogram of water of carbon dioxide, and as both the maternal and fetal plasmas lose approximately the same amount no correction has been made for this loss. The Fiske osmometer gives results in terms of milliosmols per kilogram of water with an error of ± 0.5 mOs. per kilogram of water. Results
Physiologic response to functional sympathetic denervation. Data relative to the recorded intra-arterial blood pressure of the 5 patients are presented in Table I and Fig. 1. The control systolic blood pressure of these mothers ranged between 124 and 150 mm. Hg with a mean of 135 rom. Hg. The diastolic pressure varied between 70 and 99 mm. Hg; the average for the series is 81 mm. Hg. In every instance (it is of interest to note
54 Stenger et al.
.\111.
Scptnnbc! l J9ti·l J. ()l,,f, S\ I ;)'lll'C.
Table I. Intra-arterial blood pressure changes
of subclavian vtenous prtessure of
------,-·
H~O.
Patient's
initials H. F.
F. H. ].]. S. S. L. R. Mean
I
Control
blood
Spinal
.flrpff11rP
Hflnnr''
r· ......... --.-
I (mm. Hg) 147/82 i24/70 129/76 150/99 126/78 1:35/81
,---'
Fall
(mm. Hg)
(%)
77/33 49/22 59/29 66/25 38/22 58/26
48/60 60/69 54/62 56/75 70/72 58/68
that patient F. H. received 50 mg. ephedrine intramuscularly and prior to spinal blockade) there was a dramatic and significant fall in blood pressure. The spinal "floor,'' i.e., the lowest point to which the blood pressure has descended within the first four minutes after the subarachnoid injection, reveals that the systolic pressure of these individuals now ranged between 38 and 77 mm. Hg with a mean of 58 mm. Hg. The diastolic pressure varied between 22 and 29 mm. Hg; the average for the series, 26 mm. Hg. The per cent fall in systolic pressure ranged from 48 to 70; the per cent decrease in diastolic pressure 60 to 75; and the mean drop for the entire group was 58 per cent (systolic) and 68 per cent (diastolic) . The pulse rate showed some variation. The control pulse varied from 88 to 134 beats per minute; the average 106. Following denervation, the rate ranged between 72 and 133 and the average is 86, or a mean reduction of 20 beats per minute. The pulse rate response to spinal anesthesia varied, however, both in regard to direction (one of the cases had an increase of 5) and to magnitude of response (of the 4 patients who demonstrated a bradycardia, the latter varied from 1, 9, 41, and 51 beats less than preanesthetic pulse recording) . Subclavian venous pressure determinations, complete in three of the subjects, reveal a reduction from control recordings. The latter ranged between 3.0 to 5.0 cm./H 2 0 and an average of 3.8. With sympathetic denervation there was in each instance a fall which varied from 0.0 to 3.5 cm./H20, the average now was ] .1 cm./H"O or a mean reduction
~. 7
em. ,1
Complete data on cardiac output an• available on two patients. The composite results of all the physiologic observations are presented in Fig. 2 (Patient L. R.). It may be seen that in the "control" period the blood pressure was 126/78 mm. Hg, subclavian venous pressure 3.0 cm./H~O, pulse rate 113 beats per minute, and cardiac output 6.3 liters per minute. Four minutes after functional sympathetic denervation, the blood pressure fell to 38/22 mm. Hg, subclavian venous pressure to 0.0 cm./H~O, and pulse rate to 72 beats per minute~--at this instant the cardiac output was determined and revealed a reduction of better than 3, 700 mi. per minute, or stated in another way, cardiac output was now only 41 per cent of the preanesthetic level. This latter finding is in agreement with the data of Assali and Prystowsky 1 " who demonstrated a statistically significant decrease in the cardiac output of pregnant women at the time of maximum fall in blood pressure. But it is to be men-tioned that their investigation is not directly comparable to this study for the former involved "differential spinal anesthesia,'' i.e., only the smallest fibers within the subarachnoid space are blocked, whilst larger sensory and still larger motor fibers remain functionally unaltered. 11 Although of considerable investigative worth, high spinal blockade is clinically valueless, for the usual operative spinal anesthesia depends upon the use of concentrations of local anesthetic which are adequate to block not only sympathetic fibers but also somatic sensory and motor fibers. The point to be made here is that under clinical conditions sympathetic denervation at the time of cesarean section is also associated with a decreased cardiac output. Soon after the appearance of the severe hypotension measures were introduced in order to restore the blood pressure to preanesthetic levels. The response to such therapy
is presented in Table II. It may be seen that elevation of the lower extremities, tilting of the uterus to one side, and intravenous ephedrine therapy were all employed. Re-
Volume 90 Number i
Anesthesia for cesarean section
PROTOCOL I ON BACK 20N SIDE 3EPHEDRINE I.V. 50 MGM
LEGEND .... INTRAARTERIAL BLOOD PRESSURE C>
I
~
20 ~ 16'
~
TIME
Fig. 2. Spinal anesthesia for cesarean section (Patient L. R.). Data on cardiac output, intra-arterial blood pressure, pulse rate, and venous pressure.
gardless, in 3 of the 5 cases hypotensive levels persisted and were present at the time of sampling of blood from the maternal artery and uterine vein. As a result we were provided with an opportunity to evaluate the effect of severe hypotension on uterine metabolism and maternal-fetal relationships; furthermore, there lie the possibility that we might gain insight into mechanisms, maternal and fetal, that exist when gestation is subjected to such severe stress. Characteristics of the maternal arterial and uterine venous blood. In Table III are presented the arterial, A, and uterine venous, V, oxygen contents and the calculated arteriovenous, A-V, difference. The oxygen content of the arterial blood of the pregnant mother as reported here ranges from 4.51 to 6.19 mM. per liter. Although our observations are few in number, there appeared to be no relation between status of mother and oxygen content, i.e., uncorrected hypotension 5.59 mM. per liter, corrected 4.86. With respect to the absolute volume of oxygen lost by the blood in its passage through the uterus and coefficient of oxygen utilization of
that organ (
A-V A
x 100
)
55
our data permit
comparison between the uteri of five gravidas at similar stages in pregnancy, one group in whom spinal hypotension persists and another in whom the insult of functional sympathetic denervation has been corrected. The results demonstrate that the volume of oxygen lost by the blood en route through the uterus is higher in the hypotensive patients-a feature emphasized when the coefficient of utilization is considered. In patients H. F. and F. H. (hypotension corrected), the volume of oxygen lost by the blood is uniformly small, i.e., from 0.56 to 0.59 mM. per liter; the coefficient of utilization ranged between 10.7 to 13.1. The actual quantities of oxygen lost in the other group, however, ranged from 1.21 to 2.47 mM. per liter of blood and the coefficient varies between 22.4 and 39.9. Stated in another way, the coefficient of oxygen utilization \vas 2. 7 times higher in the three patients in whom hypotension persisted. There is in the uncorrected hypotensive mother no increase in the oxygen capacity of the circulating blood over the values found in those whose blood pressure was stable (Table IV). We found the oxygen capacity of the former to average 6.73 mM. per liter with a range of 5.83 to 8.32, whereas in the latter the average was 5.97 and the range 4.81 to 7.13. The average arterial oxygen saturation in the same complicated patients was 84.2 per cent, the range from 74.4 to 92.8. In the corrected hypotensive series the average arterial oxygen saturation was 83.5 per cent; the range was from 73.1 to 93.8. It is important to mention that we are unable to explain this wide variation in the degree of arterial saturation. The pH and total C0 2 levels of the arterial and uterine venous plasmas respectively, are given in Table V together with the bicarbonate and carbon dioxide tensions are calculated for the same samples. The average value for the pH of the arterial blood is 7.44-the range from 7.40 to 7.48. The average bicarbonate content of the arterial plasma for the series is 17.8 mEq. per liter. with a
56 Stenger et al. Am.
range 16.3 to 19.2. The average of the CO~ tensions of the arterial blood is 27 .3, the individual values range between 22.7 and 30.7 mm. Hg. The data further demonstrate that the pH of the arterial blood of the hypotensive group was 0.03 units higher than the uncomplicated, that the bicarbonate was 1.0 mEq. per liter lower, and that the PC0 2 was 3.5 mm. Hg lower. In regard to the change in pH of the blood as it passes through the uterus the data presented above indicate it to be of the order of 0.02 unit (the vein lower than the artery) with a range from 0.0 to 0.6. The average value for the change in bicarbonate is 1.2 mEq. per liter (the vein
September I. 196+ J. Obst. & ( ;ynl'r'.
higher than the artery) ··-the range from 0.5 to 2. 7. The average of the CO::! tension differences of the arterial and venous bloods is 3. 7 (the vein higher than the artery), the individual values range between 1.3 and 6.0 mm. Hg. The data further demonstrate greater average changes in the uncorrected hypotensive group, i.e., the PCOc difference between the arterial and uterine venous blood averaged 5.3 mm. Hg in this series as compared to 1.3 in the uncomplicated. Similar differences in bicarbonate, plasma C0 2 , and pH between the two groups were 2.0 to 0. 7 mEq. per liter, 2.1 to 0.8 mM. per liter, and 0.04 to 0.01 unit, respectively.
Table II. Response of hypotension to corrective measures
I
Patient's £nitials
H. F.
F. H.
9:49 10:15 10:19 10:59
J.J.
9:25 9:41 ( 31 ')
s. s.
I
1
1
124/70
I
49/22 119/59
6.7
133 120
3.0 9.2
90
129/76
59/29 91/54
95 117
1'\fl/QQ
!04
.11"''-'1 .......
Intramuscular ephedrine, 50 mg. Intravenous ephedrine, 25 mg. uterus tilted corrected blood pressure Elevation legs Intravenous ephedrine, 30 mg. uncorrected blood pressure
Spinal
9:45
10:30 10:45 ( 31 ') 10:49 11:20
134 Spinal
10: 16 10:59 11:00 (29') 11:02 11 : 31
L.R.
I
Intra-arterial blood Pulse rate Cardiac output , pressure (mm. Hg) (Beats/min.) (Liters/min.) 1 Time Comment 9: 15 88 147/82 Elevation legs 9:29 Spinal Intravenous ephedrine, 10 mg. 9:31 79 corrected biood pressure 77/33 10:06 96 144/83
Intravenous ephedrine, 50 mg.
Spinal
uncorrected blood pressure 5:) 152
66/25 116/58 126/78
113
6.3
72 138
2.6 5.2
Spinal 38/22 60/31
Intravenous ephedrine, 50 mg. uncorrected blood pressure
Table III. Arterial and uterine venous oxygen contents and the calculated arteriovenous difference Coefficient of utilization
Blood O, {mM./L.)
A~V x
5.21 4.51
4.65 3.92
0.56 0.59
10.7 13.1
6.19 5.41 5.16
3.72
4.20 3.31
2.47 1.21 1.85
39.9 22.4 35.9
H. F. F. H.
.T . .T.
L. R.
(
A-V
A
s. s.
I
v
Patient's initials
100)
Volume 90 Number 1
Anesthesia for cesarean section
Table IV. Maternal blood
values~xygen
Arterial blood O, (mM./L.)
Percentage I Po: IO,saturation (mm. Hg)
Patient's initials
Capacity
H. F. F. H.
7.13 4.81
5.21 4.51
73.1 93.8
36 80
J.J.
8.32 5.83 6.04
6.19 5.41 5.16
74.4 92.8 85.4
38 70 48
S. S.
L.R.
I
57
Content
I
I I
Uterine venous blood Po: O, Content (mM./L) I 0,% Saturation 1 (mm. Hg) 65.2 4.65 32 8L5 46 3 92
I
I
24.4 36.0 27.5
44.7 72.0 54.8
3.72 4.20 3.31
Table V. Total C02 of the plasma of the arterial and uterine venous bloods, together with the pH and the calculated C0 2 tension and bicarbonate of each sample pH
Patient's initials
A
H. F. F. H.
J.J.
s. s.
L.R.
I
I
v
A
19.2 19.2
19.8 20.2
17.6 20.1 17.0
20.5 21.7 18.9
v
A
7.44 7.40
7.43 7.40
7.43 7.45 7.48
7.41 7.42 7.42
Characteristics of the umbilical arterial blood. The data on the oxygen capacity, content, and degree of oxygen saturation of the fetal bloods are presented in Table VI. The values for the oxygen capacity of bloods from the umbilical vein vary; the lowest is 6.77 and the highest 10.02 mM. per liter, and there is a tendency for the higher values to occur in the bloods of fetuses in the uncorrected hypotensive series. Correspondingly, there is a tendency for the oxygen content of the umbilical vein blood to be lower in this same group. The oxygen content of the umbilical vein bloods of the fetuses in the hypotensive series ranged from 0.94 to 3.44 mM. per liter; in the uncomplicated group the range was 3.49 to 3.98. The percentage saturation of the umbilical vein blood with oxygen averages 33.6 when the whole series of values is taken and ranges from 9.4 to 58.8 per cent. The pH of the blood in the umbilical vein varies between 7.27 and 7.40 (average 7.34) and the estimated oxygen tension from 7.2 to 23.0 mm. Hg. The average oxygen tension from the umbilical vein is 15.6 mm. Hg. When compared to the status of the mother there ap-
Pco, (mm. Hg)
HCO, (mEq./L.)
Plasma CO: (mM./L.)
I
I
v
v
A
18.4 18.3
18.9 19.2
28.0 30.7
29.3 32.0
16.8 19.2 16.3
19.5 20.7 18.1
26.3 28.7 22.7
32.0 33.0 28.7
pears to be a tendency for the tension to be lower in the uncorrected hypotensive series. The data obtained on the "total carbon dioxide" content and the C0 2 tension of the fetal bloods are presented in Table VII. The total C0 2 of the umbilical arterial blood ranges from 17.35 to 20.71 mM. per liter (average 18.49). In the plasmas the total C0 2 varied between 20.88 and 23.52 mM. per liter (average 22.11). The carbon dioxide tension in the umbilical vein blood, as calculated using the Henderson-Hasselbalch equation, ranges between 34.7 and 47.7 (average 40.8). Comment
The results presented above appear to provide for the first time data on the oxygen, carbon dioxide, and hydrogen ion concentrations of the blood entering and leaving the pregnant uterus in conjunction with similar data of umbilical vein blood in mothers who manifest severe hypotension secondary to spinal anesthesia. The circumstances that favor the increased arteriovenous oxygen differences in the uncorrected hypotensive group have not been
58
Stenger et al. \m.
St·ptt-tnh,·: 1 I~H).f. J. Oh. t. (\: ( ,YIH'C:.
Table VI. Fetal blood values-oxygen (umbilical Yein) O, (mM./L.) Patient's initials --Capa~ii-;--1---- Co~t~~t-
H. F. F. H.
6.77 7.77
:i.98 3.49
].]. S. S. L. R_
10.02 9.29 8.18
0.94 1.17 3.44
identified as yet, but we believe that they might well be attributed to a reduction in uterine blood flow-a reasonable assumption, granted the same rate of oxygen consumption of the uterus and its contents in the brief period of experimental observation. Associated with the increased A-V oxygen difference there is an increased Pco~ difference (uterine vein-maternal artery) across the uterus. As oxygen and carbon dioxide appear to move across the placental barrier by diffusion these differences in their concentrations in the uterine capillaries can be expected to affect the rate of their exchange between the two circulations-maternal and fetal. The nature of these changes in fetal blood have been shown to consist of an increased oxygen capacity, reduced oxygen content, and decreased percentage oxygen saturation. In regard to carbon dioxide we have found an increased transplacental gradient. The differences in the carbon dioxide tension in the maternal blood entering the uterus and in the arterialized blood of the fetus are shown in Table VIII. The average value in the corrected hypotensive group is 9.0 mm. Hg (range 7.0 to 11.0) . In the uncorrected the average difference is 16.5 and the range 12.0 to 19.0. It is our feeling that in the uncorrected hypotensive gravidas we have described the oxygen supply might well have been compromised-an inference which gains further support from our observations on the total osmotic pressure of the maternal and fetal plasmas of these same individuals. In the course of our observations we have noted that acute insult to the mother resulted in a rise
0, Percentage
saturation
pH
58.8
H.9
7.40 7.34
9.4 12.6 42.1
7.27 7.29 7.38
Po, (mnz. Hg)
7.2 9.5 18.1
m the total osmotic pressure of the fetal plasma with respect to the maternal ( 15 m0s./Kg./H 2 0) . When the maternal blood pressure had been corrected to prespinal levels the total osmotic pressure of the fetal plasma was slightly higher than that of the maternal (5 m0s./Kg./H 2 0). As reported by Meschia and colleagues, 1 " this measurement might well serve as a most sensitive indicator of fetal hypoxia. The physiological effects of spinal anesthesia are due solely to the preganglionic sympathetic block produced by the technique Exceptions to this statement are infrequent; hence, the cardiovascular and occasional respiratory alterations produced by this procedure cannot be ascribed to direct depression of brain stem centers by the local anesthetic. In those rare instances in which respiratory inadequacy or arrest occurs, it is more frequently due to an ischemic depression of the medullary respiratory center than due to phrenic paralysis. 13 That skeletal muscle paralysis has no effect on venous return or cardiovascular function is demonstrated by the fact that equally profound muscle relaxation produced by interference with normal myoneural junction transmission following succinylcholine administration is unattended by cardiovascular effects. At this point it is well to recall the fact that the level of sympathetic denervation extends two or as many as six spinal segments beyond the level of sensory anesthesia during spinal blockade. 14 Accordingly, it is often difficult-if not impossible-to relate sensory levels of anesthesia to physiological changes with any degree of precision. Moreover, since each preganglionic sympathetic fiber synapses
Volume 90 Number 1
in the paravertebral sympathetic chain with as many as 22 postganglionic sympathetic fibers 15 and since each postganglionic fiber is distributed to the periphery in a non-segmental manner, block of a single preganglionic sympathetic fiber during spinal anesthesia results in a peripheral sympathetic paralysis which is not only diffuse but also bears no relation to peripheral segmental sensory distribution. For these reasons the sympathetic denervation accompanying spinal anesthesia is often surprisingly extensive. In pregnant women the response to blockade might well be aggravated, for it has been shown 16 that in normal pregnancy the blood pressure is maintained mainly by neurogenic impulses. Spinal anesthesia produces arterial and arteriolar vasodilatation17 ; there results increases in pulse volume 18 and in peripheral arterial pulse wave contour. 19 The degree to which arteries and arterioles vasodilate varies in different types of tissues, and the important point to be made here is that the vasodilatation results in relatively insignificant changes in total peripheral vascular resistance. One reason for the failure of peripheral vascular resistance to decrease markedly is that compensatory vasoconstriction occurs in sympathetically intact areas. 20 Moreover, there is still resistance to peripheral flow of blood through postarteriolar vessels--the major site of resistance is shifted peripherally21 but resistance is not eliminated. Changes in total peripheral resistance during spinal anesthesia are neither as frequent nor as profound as often assumed. Severe decreases in arterial pressure, as we have noted in our study group, must be due to additional factors. Although it is impossible to make categorical statements on postarteriolar denervation, it has been demonstrated that neurogenic impulses play an ever decreasing role in vascular homeostasis as the postarteriolar bed is approached. 22 It is of critical importance, however, to recognize the fact that sympathetic nerves innervate veins and denervation is capable of producing venous hemodynamic changes. After blockade of an artery there is con-
Anesthesia for cesarean section 59
Table VII. Fetal blood and plasma valuescarbon dioxide (umbilical vein) Patient's initials
Blood (mM./L. CO,)
Plasma (mM./L. CO,)
Pco, (mm. Hg)
H. F. F. H.
18.13 17.35
22.02 23.01
35.0 41.7
J.J.
18.32 20.71 17.92
21.12 23.52 20.88
44.7 47.7 34.7
s. s.
L. R.
Table VIII. C0 2 tension (mm. Hg)
Ill
maternal artery and umbilical vein
Maternal artery
Umbilical vein
Difference umbilical vein to maternal artery
H. F. F. H.
28.0 30.7
35.0 41.7
7.0 11.0
J.J.
26.3 28.7 22.7
44.7 47.7 34.7
18.4 19.0 12.0
Patient's initials
S. S.
L.R.
siderable residual smooth muscle tone, whereas in the vein there is little or no residual tone. The degree of venodilation in denervated veins is a function of the volume of blood within the vein and, in turn, this is a function of intraluminal hydrostatic pressures determined primarily by gravity. If a sufficiently large number of denervated veins is below the level of the right auricle, the consequent peripheral pooling of blood and decrease in effective circulating blood volume have effects of greater importance in determining the physiological response to spinal anesthesia than any of the events taking place in the arterial or postarteriolar circulations because of profound effects on cardiac output. Stated in another way, the effects of preganglionic sympathetic denervation on cardiac output are determined by changes in venous return to the heart. All investigators are agreed that spinal anesthesia decreases cardiac output2 3-this statement may now be extended to the preg-
September 1. 196+
60 Stenger et al.
nant patient under clinical circumstances. The decrease is accompanied by a corresponding decrease in right auricular pressure. 24 The most important single determinant of mean aortic pressure during spinal anesthesia is cardiac output! Only when cardiac output falls is the arterial hypotension of sympathetic denervation found to be severe. In view of the relationship between venous return and cardiac output the maintenance of an adequate venous return becomes the sine qua non for the safe management of the patient with impaired activity of the sympathetic nervous system. The use of the slight head-down position, elevation of the lower extremities, tilting of the uterus to one side have all been recommended but clearly the most popular procedure is the administration of drugs which restore smooth muscle tone to denervated veins, thereby preventing peripheral pooling of blood. The concept that vasopressors raised arterial blood pressure by increasing cardiac output and/or peripheral resistance is inadequate for it is apparent that even a drug with a strongly positive inotropic effect cannot increase cardiac output and blood pressure in the presence of an inadequate venous return and an inadequate ventricular diastolic filling. Also, since the decrease in peripheral resistance during sympathetic blockade can account for on the average only 13 per cent of an observed decrease in arterial blood pressure, restoration of a pressure which has fallen 40 per cent cannot be solely the result of increased peripheral resistance. Accordingly, it is now accepted that a significant portion of the vascular response to vasopressors is due to their constricting effect on the venous circulation. There are aspects of the vasopressor situation which are disturbing to us. First, we have not been able to correct the hypotension induced in pregnant women in every instance; nor have we been successful in preventing hypotension by the use of prophylactic medication. Moya 25 also reports that of a series of 1,141 gravid patients who received ephedrine prophylactically, 46 per cent had
Am.
J.
Obst. & Gym·c.
falls in blood pressure exceeding 20 per cent of the preanesthetic level, and in more than half of the cases the systolic pressure fell below 100 mm. Hg. Second, there is recent evidence that vasoconstrictors may indeed reduce uterine blood flow. 26 Bradycardia is a characteristic finding during the sympathetic denervation of spinal anesthesia. It has been hypothesized that the slow pulse rate is due to preganglionic block of the cardiac accelerator fibers-an inadequate explanation. The primary reason is change in central venous pressure and right auricular pressures. 27 Moreover, there is a direct correlation between decrease in pulse rate and decrease in arterial blood pressurethe common denominator linking them under these conditions is, of course, venous return. Summary
The choice of anesthesia in the pregnant patient is of real significance. Indeed the unique sensitivity of the fetus to the effects, or occasional side effects, of abnost all forms of maternal anesthesia poses one of the most difficult problems in obstetrics. On the one hand, it is essential to employ an agent that will allow the safe and satisfactory execution of the technical procedures involved; on the other, it is also important to be mindful of the especial vulnerability of the respiratory center of the fetus to various anesthetics. It is well known that certain agents, whether they be inhaled or be given systemically, traverse the placenta and there rises the possibility of jeopardizing the respiratory behavior of the newborn. For other reasons also, in the recent past there has been a trend toward and widespread acceptance of conduction anesthesia for cesarean section; in this category the subarachnoid approach enjoys the greatest popularity. The purpose of this communication is not to advocate that spinal anesthesia for cesarean section be discontinued, nor is it intended to belittle the advantages of the technique. Its main aim is to point out that there are real dangers-both maternal and fetal.
Volume 90 Number 1
Anesthesia for cesarean section
61
REFERENCES
1. Stenger, V., Andersen, T., Eitzman, D., Gess· ner, I., De Padua, C., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 87: 1037, 1963. 2. Stenger, V., Eitzman, D., Andersen, T., De Padua, C., Gessner, I., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 88: 45, 1964. 3. Stenger, V., Eitzman, D., Gessner, 1., Andersen, T., De Padua, C., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 87: 1042, 1963. 4. Kinsman, J, M., Moore, J. W., and Hamilton, W. F.: Am. J. Physiol. 89: 322, 1929. 5. Van Slyke, D. D., and Neill, J. M.: J. Bioi. Chern. 61: 523, 1924. 6. Prystowsky, H., and Eastman, N. J.: Bull. Johns Hopkins Hosp. 101: 45, 1957. 7. Prystowsky, H., Hellegers, A., Cotter, J., and Bruns, P.: AM. J. 0BsT. & GvNEC. 77: 585, 1959. 8. Prystowsky, H., Hellegers, A., and Bruns, P.: AM. J. 0BST. & GYNEC. 78: 489, 1959. 9. Prystowsky, H., Hellegers, A., and Bruns, P.: Obst. & Gynec. 15: 778, 1960. 10. Assali, N. S., and Prystowsky, H.: J. Clin. Invest. 29: 1367, 1950. 11. Sarnoff, S. J., and Arrowood, J. G.: Surgery 20: 150, 1946. 12. Meschia, G., Battaglia, F., and Barron, D. H.: Quart. J. Exper. Physiol. 42: 164, 1957. 13. Greene, N. M.: Physiology of Spinal Anes·
Discussion DR. S. LEON IsRAEL, Philadelphia, Pennsyl· vania. In studying the manuscript sent to me by Doctor Prystowsky several months in advance of this meeting, I was reminded constantly of the present-day facility with which scientists tell of their work as well as of the continuing difficulty experienced by others who must struggle to understand them because of a lack of easy, daily familiarity with the jargonautic ambience of such reports. In this vein, Robert Oppenheimer has recently explained that the effectiveness of the converse between specialists within a profession hinges upon problems "having to do just with communication and comprehension-understanding-of scientific knowledge." 4 For this reason, my discussion will be that of an obstetrician but of one devoted to the use of properly administered spinal anesthesia for cesarean section. Any critical references to the biochemical measurements reported by the essayists will not be those of a physiologist but rather of a clinician interpreting data with which he is not called upon to cope daily. The material presented this morning reflects Prystowsky's decade-long interest in the physiol-
14. 15. 16. 17. 18. 19. 20. 21.
22. 23. 24. 25. 26. 27.
thesia, Baltimore, 1958, Williams & Wilkins Co. Greene, N. M.: Anesthesiology 19: 45, 1958. White, J, C., Smithwick, R. H., and Simeone, F. A.: The Autonomic Nervous System, ed. 3, New York, 1952, The MacMillan Company. Assali, N. S., and Prystowsky, H.: J. Clin. Invest. 29: 1354, 1950. Lee, W. C., and Shideman, F. E.: Circulation Res. 6: 66, 1958. Neuman, C., Foster, A. D., and Rovenstine, E. A.: J. Clin. Invest. 24: 345, 1945. Eather, K. F., Peterson, L. H., and Dripps, R. D.: Anesthesiology 10: 125, 1949. Milwidsky, H., and de Vries, A.: Anesthesiology 9: 258, 1948. Haddy, F. J., and Gilbert, R. P.: Circulation Res. 4: 25, 1956. Zweifach, B. W.: Am. J. Med. 23: 684, 1957. Smith, H. W., Rovenstine, E. A., Goldring, W., Chasis, H., and Ranges, H. A.: J. Clin. Invest. 18: 319, 1939. Lynn, R. B., Sancetta, S. M., Simeone, F. A., and Scott, R. W.: Surgery 32: 195, 1952. Moya, F., and Smith, B.: J. A. M. A. 179: 609, 1962. Huckabee, W.: Personal communication. Pugh, L. G. C., and Wyndham, C. L.: Clin. Sci. 9: 189, 1950.
ogy of fetomaternal relations and his persistent effort to clarify the factors that govern the placenta's two-way transfer of gases in solution. The changing physical as well as geographic circumstances in which his investigations have been accomplished truly represent the "pursuit of knowledge under difficulties." In this study, he and his colleagues have attempted to demonstrate the effects of maternal hypotension upon the oxygen available to and used by the fetus. It is not difficult to accept the theses that the degree of hypotension following spinal anesthesia varies directly with the magnitude of sympathetic blockade; that uncorrected hypotension results in lowering of subclavian venous pressure as well as reduced cardiac output; that such physiologic alterations produce a slower blood flow within the uterus, permitting its tissues a longer period of time to extract oxygen from that blood; and that this alone eventuates in a lower oxygen content of uterine venous blood than that coming from a uterus in the absence of hypotension. The so-called "coefficient of oxygen utilization" is thus increased-a magnificent evidence of the body's physiologic economy, one
62 Stenger et al.
of its accommodating responses to maintain the all-important level of tissue oxygen in spite of reduced blood flow. Under such compensating circumstances, it is, likewise, no surprise to note the increased oxygen capacity of fetal blood. That such augmentation of the oxygen capacity of fetal blood is normal under conditions of stress was well documented by Low,:l whose investigations showed significant elevation of oxygen capacity in the fetus subjected to normal uterine contractions during vaginal delivery in contrast to that of the fetus delivered by cesarean section. Such enhancement-attributed by Born, Dawes and Mott 2 in their study of anoxia in lambs to splenic contracture and by Walker and Turnbull 5 in their investigation of umbilical cord hemoglobin levels to fetal hematopoiesis-~ probably helps to account for the astounding fact that the fetus of the markedly hypotensive patient, L. R., was able to transfer sufficient oxygen from the intervillous space to its umbilical vein. However, although we may congratulate such a fetus upon its ability to avert disaster by instantaneous accommodation, we still lack comprehension of its method. It is evident that the essayists, in their search for elucidation, are sensible to the complexity of their manifold calculations as well as of the difficulty in attaining meaningful interpretation of observations made in but five patients. They have, for instance, taken osmotic pressure as wt>IJ as pH into account. Their osmotic pressure data are of particular interest inasmuch as each of the patients received an intravenous infusion of 5 per cent solution of dextrose in watt>r continuously during the time of spinal anestht>sia. Since shifts of water in plasma can change oxygen capacity, 1 one wonders whether the hypotensively induced reduction of uterine blood flow could have also affected the fetomaternal exchange of dextrose solution and thus accounted
for the altered osmotic pressures. When maternal blood pressure was restored, the osmotic pressure of fetal plasma increased. Do('s this, perhaps, merely reflect better transfer of the administered dextrose as a result of improved uterine flow? It should be emphasized that the use of such intravenous therapy is imperative for the proper administration of spinal anesthesia for cesarean section. We have observed the drop of blood pressure to occur as late as 10 minutes after initiation of spinal anesthesia, not-as the essayists have stated-4 minutes. Because this fall rnay be drarnatic and cannot be predicted, we likewise pstablish suitable intravenous infusion
.\m.
.',q>tt'mht"'t 1. IYfi-t ,r. Ob.;r. & f;ynPc.
before the spinal anesthesia is administered; at the time of intrathecal inj1~ction of the anesthetic agent, 10 mg. of methamphetamine hydrochloride are given intravenously. If the pulse rate is above 100, we substitute 4 mg. of methoxamine hydrochloride for the methamphetamine. The intravenous route insures that the drug has entered the circulation, that its maximum effect will be produced within 5 minutes, and that the major response to it will have worn off by the time the postdelivery oxytocic is given, lessening the risk of disturbing hypertension. In our management, the danger of uncontrollable hypotension is slight. Finally, as an obstetrician, I must ask a practical question of Dr. Prystowsky, for he has tantalizingly failed to give us clinical information concerning the infant of J. J., whose umbilical vein biochemically had a literal absence of oxygen (Table VI), suggesting severe deprivation. We must not forget in our scrutiny of twigs and leaves on the many branches that a for~st has trees. Will Dr. Prystowsky please relate that baby's birth-room condition as well as its eventual neonatal outcome? REFERENCES
1. Battaglia, F.,
Prystowsky, H., Smisson, C., Hellegers, A., and Bruns, P.: Pediatrics 25: 1, 1960.
2. Born, G. \r. R., Dawes, G. S., and Mottl J. C.: ]. Physiol. 134: 149, 1956. 3. Low, ]. A.: Obst. & Gynec. 20: 363, 1962. 4,. Oppenheimer, R.: Science 142: 1143, 1963. 5. Walker, J., and Turnbull, E. P. N.: Lancet 2: 312, 1953. 807 Spruce Street Philadelphia, Pennsylvania 19107
DR. jACOB RozrER,* Winter Park, Florida. There are a few questions that come to mind. Mention of sensory level of anesthesia obtained is not recorded, but it is pointed out that the sympathetic level of anesthesia does run much higher than the sensory level. Moya 1 reported that 46 per cent of cesarean sections with spinal anesthesia exhibited a greater than 20 per cent fall in blood pressure. Moya also pointed out that pressure of the uterus on the vena cava is probably responsible for the lowered cardiac output and hypotension in I 2 per cent of cases in which tht> blood pressure falls below 100 mm. Hg systolic. Hingson 2 likewise stated that uterine pressure on the vena cava is a probable cause of hypo-
*By invitation.
Volume 90 Number 1
tension and further stated that profound hypotension is twice as frequent in anemic patients. I would assume that anemia was not a factor in the case studied. It would have been interesting to have had continuous fetal electrocardiographs since Hon 3 states that the fetal heart shows definite pathologic bradycardia of a hypoxic type within a few minutes after the maternal blood pressure drops below 100 mm. Hg systolic. In review of the cesarean sections done during the last years under spinal anesthesia at the Winter Park Hospital where all spinals were given by trained anesthesiologists there seems to have been little hypotension. Thirty-two per cent of patients showed a fall of 15 per cent in blood pressure but 3 per cent dropped below 100 mm. Hg systolic. All live born babies had an Apgar score of 8 to 10. One stillborn infant resulted from complete abruptio placentae. It is
Anesthesia for cesarean section
63
not the policy of the anesthesiologist to give a preoperative prophylactic vasopressor. We have certainly not been presented with such problems of hypotension as the essayist describes for, otherwise, I would be looking for another and safer type of anesthesia. The preoperative maternal arterial oxygen saturation, not given in this paper, would have been interesting to know for comparison with the oxygen saturations during hypotension, commenting upon which the authors state that "we are unable to explain this wide variation in the degree of arterial saturation." REFERENCES
1. Moya, F., and Smith, B.: J. A. M. A. 179: 609, 1962. 2. Hingson, R. T., and Cull, W. A.: Clin. Obst. & Gynec. 4: 104, 1961. 3. Hon, E. H., and Chung, F.: Obst. & Gynec. 13: 633, 1959.
VINCENT STENGER, M.D. THORKILD .A.. ~~DERSE~~'
~1.D.
CONSTANTE DE PADUA, M.D. DONALD EITZMAN, M.D. IRA GESSNER, M.D. HARRY PRYSTOWSKY, M.D. Gainesville, Florida
THE PLAcENTA presents itself as a tissue barrier that separates the maternal and fetal bloods. All materials that move from one circulation to the other must cross that barrier. This movement may be accomplished in different ways. The respiratory gases. cross by diffusion; they move from the plasma of higher concentration to the plasma with the lower. The degree to which this tissue barrier of the placenta restricts or promotes the movement of materials to the fetal circulation must affect their availability to the fetus and the degree to which the barrier limits or promotes movement from the fetal blood must be reflected in the composition of the fetal internal environment. Accordingly, the interest of the physiologist and the ciinician centers about such questions as the following: What is the normal limitation placed by the
tissue barrier upon the free movement of oxygen and carbon dioxide from one circulation to the other; what are the consequences and signs of an increase in that limitation; and, finally, what measures may be taken when the limitation exceeds a normal range to improve the position of the fetus? The data presented here on spinal anesthesia for cesarean section were obtained as a part of a wider investigation of the oxygen supply to the human fetus. As the first step in this program we estimated the arteriovenous oxygen difference across the human pregnant uterus at selected stages in gestation.1 Next we examined the characteristics of fetal and maternal bloods in regard to the blood gases, 2 total osmotic pressure, sodium, and potassium concentrations.' During the course of our study we soon became aware of the profound changes which occurred when functional sympathetic denervation was carried out at the time of elective cesarean section and realized that such circumstances provided us with an opportunity to evaluate the effect of severe maternal hypotension on maternal-fetal relationships and an opportunity to gain insight into mechanisms, maternal and fetal, that exist when gestation is subjected to acute stress. Although the number of patients evaluated is few, the data are complete and reproducible,
From the Departments of Obstetrics and Gynecology, Anesthesiology, and Pediatrics, University of Florida College of Medicine.
This research was supported in part by United States Public Health Service Grants HD-00546-02, H-7129. and 2A 5273. . . Presented by invitation at the Twentysixth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Bal Harbour, Florida, fan. 26-29, 1964.
51
52
Stenger et al.
and certain points of interest emerge from them with sufficient clarity that we do not hesitate to present them at this time. Material and methods
Our observations were made at the University of Florida Teaching Hospital. The 5 patients studied were delivered by cesarean section; 4 were normotensive and 1 had essential hypertension. All were operated upon between the thirty-eighth and fortieth weeks of gestation. Each individual was prepared for study in the following manner: in the supine position and under local anesthesia (Xylocaine 1 per cent) Cournand needles were placed in the radial arteries. A catheter was inserted in an antecubital vein and threaded up to the level of the subclavian vein. Electrocardiographic (EKG) leads were placed. Connection was then made between one artery, the vein, and the EKG equipment with a four channel recorder. The other radial artery was prepared so that it could be utilized for apparatus designed to measure cardiac output in a repetitive manner and at short intervals, i.e., dye dilution technique. 4 Each patient served as her own control. Our procedure was as follows: a continuous recording of intra-arterial blood pressure, EKG, venous pressure, pulse rate, a determination of cardiac output, and collection of 20 mi. of maternal arterial blood in a heparinized and oiled syringe were first obtainedthe so-called "control" period. The single dose technique of spinal anesthesia was then administered. The patient was placed in the left lateral decubitus position while receiving an infusion of 5 per cent dextrose in water. The operating table was adjusted so that the vertebral column was parallel to the floor. A diminution of the lumbar spinal curvature was then effected by having the patient held in complete flexion by an assistant. The lower back was then prepared \Vith tincture of zephiran and draped in sterile fashion. With a stock solution of 1 per cent procaine and a standard No. 26 gauge needle on a 2 mi. syringe a skin wheal was raised in the midline over
Am.
September l, 1964 J Obst. & Gynec.
the interspace between lumber 3 and lumbar 4. Using a No. 22 gauge needle and the same syringe, the interspace was infiltrated with the 1 per cent procaine to the depth of the ligamentum flavum. A midline intrathecal puncture was then made with a No. 26 gauge 3 inch spinal needle with the bevel directed downward. The previously prepared mixture of 0.8 ml. (8 mg.) of pontocaine and 0.8 mi. ( 80 mg.) of 10 per cent dextrose was administered in a steady stream with constant pressure. The spinal needle was then removed and the patient immediately placed in the supine position with a folded pillow under her head. Deep Trendelenburg position was not employed. In one individual 50 mg. of ephedrine was given intramuscularly prior to the anesthesia--mention will be made of this case later in the presentation. Immediately thereafter a second series of recordings, cardiac output determination, and maternal arterial blood collection was carried out. Thereafter, the recording of venous pressure, intra-arterial blood pressure, EKG, and pulse rate were continuous; cardiac output evaluations were likewise repeated. Through a lower midline incision the peritoneal cavity was entered. The uterus was then gently rotated to one side. Another cardiac output was determined. A No. 20 gauge needle attached to a heparinized and oiled syringe was then inserted into one of the large tributaries of the uterine vein which lie lateral to the uterus. Twenty milliliters of blood were then simultaneously collected from the uterine vein and the maternal artery. The uterus was then incised and the fetus delivered. After clamping the umbilical cord, the umbilical vein was sampled immediately at the operating table. In this presentation we shall only be concerned with specimens simultaneously collected from the maternal artery and uterine vein, and the umbilical vein at the moment of delivery. After each collection of blood, the syringe was capped and immediately placed into a beaker containing ice and water. Analyses were performed immediately after the ter-
Anesthesia for cesarean section
Volume 90 Number 1
ruination of the experiment, i.e., within 30 minutes. The oxygen and carbon dioxide contents of each sample were determined in duplicate on 0.5 ml. specimens by the method of Van S!yke and Neill. 5 The oxygen capacity was measured by the same technique as described in a previous paper. 6 The percentage saturation of the blood was calculated by dividing oxygen capacity into oxygen content and multiplying by 100, i.e., (oxygen content -;oxygen capacity) x (100) =percentage saturation. The saturation was then referred to an appropriate oxygen dissociation curve 7 • 8 9 • ; in this manner the partial pressure of oxygen ( p0 2 ) in each sampie was estimated. Another aliquot of the blood sample was transferred to a centrifuge tube under oil, and cells and plasma were separated by centrifugation at 3,000 r.p.m. for 45 minutes. The carbon dioxide content of each plasma sample drawn from the centrifuge tube and transferred to the Van Slyke pipette by means of an oiled syringe was determined in duplicate by the manometric method of Van Slyke and Neill 5 on 0.5 ml. samples. The pH of each specimen was determined by means of a Beckman expanded scale meter, Model 76, which had been set at 37° C. and previously standardized with a buffer of known pH. (The reading error was ± 0.01 units.) Knowing the total carbon dioxide content and pH of each plasma sample, the physically dissolved carbon dioxide was calculated from the Henderson-Hasselbalch equation: pH
= 6 · 10 + log
total C02"·dissolved C02 dissolved COz
The carbon dioxide tension in millimeters of mercury was then calculated from the dissolved carbon dioxide by means of the Bunsen coefficient, i.e., dissolved C0 2 /0.0301) = pC0 2 , where 0.0301 is the quantity of carbon dioxide in rnillimols, dissolved in 1 liter of plasma at standard temperature and pressure per rnm. Hg of carbon dioxide tension, and where the concentration of dissolved carbon dioxide is also expressed in rnillimols per liter. Another part of the plasma sample was
SPINAL ANESTHESIA FOR
CESAREAN SECTION-
THE INTRAARTERIAL BLOOD PRESSURE
! Re.stin9
i60~ 150 140
~ 130~
!
120
~
"110
~
:::
Q:"
".!!
100 90
Q
"'
80
C;
70
~
60
Q
50
·~
.::"
.!: 4n
~~~
I
i
"Spinal Floor"
l I
r l I
lj ll II
l
II
20
II I
10 0 Potient
11.F.
J.J.
RESPONSE
Control BP
r
I
53
s.s.
Ul.
I
l
I II
j
I
I L!J I F. H.
Fig. 1.
used for determination of freezing point. The measurement \vas made \vith a Fiske osmom= eter on 2 ml. specimens. The samples, previously cooled to 4° C., were transferred directly from the syringes in which they were stored by means of a long needle to the bottom of a test tube. Treated in this manner the plasma loses no more than 1 mOs. per kilogram of water of carbon dioxide, and as both the maternal and fetal plasmas lose approximately the same amount no correction has been made for this loss. The Fiske osmometer gives results in terms of milliosmols per kilogram of water with an error of ± 0.5 mOs. per kilogram of water. Results
Physiologic response to functional sympathetic denervation. Data relative to the recorded intra-arterial blood pressure of the 5 patients are presented in Table I and Fig. 1. The control systolic blood pressure of these mothers ranged between 124 and 150 mm. Hg with a mean of 135 rom. Hg. The diastolic pressure varied between 70 and 99 mm. Hg; the average for the series is 81 mm. Hg. In every instance (it is of interest to note
54 Stenger et al.
.\111.
Scptnnbc! l J9ti·l J. ()l,,f, S\ I ;)'lll'C.
Table I. Intra-arterial blood pressure changes
of subclavian vtenous prtessure of
------,-·
H~O.
Patient's
initials H. F.
F. H. ].]. S. S. L. R. Mean
I
Control
blood
Spinal
.flrpff11rP
Hflnnr''
r· ......... --.-
I (mm. Hg) 147/82 i24/70 129/76 150/99 126/78 1:35/81
,---'
Fall
(mm. Hg)
(%)
77/33 49/22 59/29 66/25 38/22 58/26
48/60 60/69 54/62 56/75 70/72 58/68
that patient F. H. received 50 mg. ephedrine intramuscularly and prior to spinal blockade) there was a dramatic and significant fall in blood pressure. The spinal "floor,'' i.e., the lowest point to which the blood pressure has descended within the first four minutes after the subarachnoid injection, reveals that the systolic pressure of these individuals now ranged between 38 and 77 mm. Hg with a mean of 58 mm. Hg. The diastolic pressure varied between 22 and 29 mm. Hg; the average for the series, 26 mm. Hg. The per cent fall in systolic pressure ranged from 48 to 70; the per cent decrease in diastolic pressure 60 to 75; and the mean drop for the entire group was 58 per cent (systolic) and 68 per cent (diastolic) . The pulse rate showed some variation. The control pulse varied from 88 to 134 beats per minute; the average 106. Following denervation, the rate ranged between 72 and 133 and the average is 86, or a mean reduction of 20 beats per minute. The pulse rate response to spinal anesthesia varied, however, both in regard to direction (one of the cases had an increase of 5) and to magnitude of response (of the 4 patients who demonstrated a bradycardia, the latter varied from 1, 9, 41, and 51 beats less than preanesthetic pulse recording) . Subclavian venous pressure determinations, complete in three of the subjects, reveal a reduction from control recordings. The latter ranged between 3.0 to 5.0 cm./H 2 0 and an average of 3.8. With sympathetic denervation there was in each instance a fall which varied from 0.0 to 3.5 cm./H20, the average now was ] .1 cm./H"O or a mean reduction
~. 7
em. ,1
Complete data on cardiac output an• available on two patients. The composite results of all the physiologic observations are presented in Fig. 2 (Patient L. R.). It may be seen that in the "control" period the blood pressure was 126/78 mm. Hg, subclavian venous pressure 3.0 cm./H~O, pulse rate 113 beats per minute, and cardiac output 6.3 liters per minute. Four minutes after functional sympathetic denervation, the blood pressure fell to 38/22 mm. Hg, subclavian venous pressure to 0.0 cm./H~O, and pulse rate to 72 beats per minute~--at this instant the cardiac output was determined and revealed a reduction of better than 3, 700 mi. per minute, or stated in another way, cardiac output was now only 41 per cent of the preanesthetic level. This latter finding is in agreement with the data of Assali and Prystowsky 1 " who demonstrated a statistically significant decrease in the cardiac output of pregnant women at the time of maximum fall in blood pressure. But it is to be men-tioned that their investigation is not directly comparable to this study for the former involved "differential spinal anesthesia,'' i.e., only the smallest fibers within the subarachnoid space are blocked, whilst larger sensory and still larger motor fibers remain functionally unaltered. 11 Although of considerable investigative worth, high spinal blockade is clinically valueless, for the usual operative spinal anesthesia depends upon the use of concentrations of local anesthetic which are adequate to block not only sympathetic fibers but also somatic sensory and motor fibers. The point to be made here is that under clinical conditions sympathetic denervation at the time of cesarean section is also associated with a decreased cardiac output. Soon after the appearance of the severe hypotension measures were introduced in order to restore the blood pressure to preanesthetic levels. The response to such therapy
is presented in Table II. It may be seen that elevation of the lower extremities, tilting of the uterus to one side, and intravenous ephedrine therapy were all employed. Re-
Volume 90 Number i
Anesthesia for cesarean section
PROTOCOL I ON BACK 20N SIDE 3EPHEDRINE I.V. 50 MGM
LEGEND .... INTRAARTERIAL BLOOD PRESSURE C>
I
~
20 ~ 16'
~
TIME
Fig. 2. Spinal anesthesia for cesarean section (Patient L. R.). Data on cardiac output, intra-arterial blood pressure, pulse rate, and venous pressure.
gardless, in 3 of the 5 cases hypotensive levels persisted and were present at the time of sampling of blood from the maternal artery and uterine vein. As a result we were provided with an opportunity to evaluate the effect of severe hypotension on uterine metabolism and maternal-fetal relationships; furthermore, there lie the possibility that we might gain insight into mechanisms, maternal and fetal, that exist when gestation is subjected to such severe stress. Characteristics of the maternal arterial and uterine venous blood. In Table III are presented the arterial, A, and uterine venous, V, oxygen contents and the calculated arteriovenous, A-V, difference. The oxygen content of the arterial blood of the pregnant mother as reported here ranges from 4.51 to 6.19 mM. per liter. Although our observations are few in number, there appeared to be no relation between status of mother and oxygen content, i.e., uncorrected hypotension 5.59 mM. per liter, corrected 4.86. With respect to the absolute volume of oxygen lost by the blood in its passage through the uterus and coefficient of oxygen utilization of
that organ (
A-V A
x 100
)
55
our data permit
comparison between the uteri of five gravidas at similar stages in pregnancy, one group in whom spinal hypotension persists and another in whom the insult of functional sympathetic denervation has been corrected. The results demonstrate that the volume of oxygen lost by the blood en route through the uterus is higher in the hypotensive patients-a feature emphasized when the coefficient of utilization is considered. In patients H. F. and F. H. (hypotension corrected), the volume of oxygen lost by the blood is uniformly small, i.e., from 0.56 to 0.59 mM. per liter; the coefficient of utilization ranged between 10.7 to 13.1. The actual quantities of oxygen lost in the other group, however, ranged from 1.21 to 2.47 mM. per liter of blood and the coefficient varies between 22.4 and 39.9. Stated in another way, the coefficient of oxygen utilization \vas 2. 7 times higher in the three patients in whom hypotension persisted. There is in the uncorrected hypotensive mother no increase in the oxygen capacity of the circulating blood over the values found in those whose blood pressure was stable (Table IV). We found the oxygen capacity of the former to average 6.73 mM. per liter with a range of 5.83 to 8.32, whereas in the latter the average was 5.97 and the range 4.81 to 7.13. The average arterial oxygen saturation in the same complicated patients was 84.2 per cent, the range from 74.4 to 92.8. In the corrected hypotensive series the average arterial oxygen saturation was 83.5 per cent; the range was from 73.1 to 93.8. It is important to mention that we are unable to explain this wide variation in the degree of arterial saturation. The pH and total C0 2 levels of the arterial and uterine venous plasmas respectively, are given in Table V together with the bicarbonate and carbon dioxide tensions are calculated for the same samples. The average value for the pH of the arterial blood is 7.44-the range from 7.40 to 7.48. The average bicarbonate content of the arterial plasma for the series is 17.8 mEq. per liter. with a
56 Stenger et al. Am.
range 16.3 to 19.2. The average of the CO~ tensions of the arterial blood is 27 .3, the individual values range between 22.7 and 30.7 mm. Hg. The data further demonstrate that the pH of the arterial blood of the hypotensive group was 0.03 units higher than the uncomplicated, that the bicarbonate was 1.0 mEq. per liter lower, and that the PC0 2 was 3.5 mm. Hg lower. In regard to the change in pH of the blood as it passes through the uterus the data presented above indicate it to be of the order of 0.02 unit (the vein lower than the artery) with a range from 0.0 to 0.6. The average value for the change in bicarbonate is 1.2 mEq. per liter (the vein
September I. 196+ J. Obst. & ( ;ynl'r'.
higher than the artery) ··-the range from 0.5 to 2. 7. The average of the CO::! tension differences of the arterial and venous bloods is 3. 7 (the vein higher than the artery), the individual values range between 1.3 and 6.0 mm. Hg. The data further demonstrate greater average changes in the uncorrected hypotensive group, i.e., the PCOc difference between the arterial and uterine venous blood averaged 5.3 mm. Hg in this series as compared to 1.3 in the uncomplicated. Similar differences in bicarbonate, plasma C0 2 , and pH between the two groups were 2.0 to 0. 7 mEq. per liter, 2.1 to 0.8 mM. per liter, and 0.04 to 0.01 unit, respectively.
Table II. Response of hypotension to corrective measures
I
Patient's £nitials
H. F.
F. H.
9:49 10:15 10:19 10:59
J.J.
9:25 9:41 ( 31 ')
s. s.
I
1
1
124/70
I
49/22 119/59
6.7
133 120
3.0 9.2
90
129/76
59/29 91/54
95 117
1'\fl/QQ
!04
.11"''-'1 .......
Intramuscular ephedrine, 50 mg. Intravenous ephedrine, 25 mg. uterus tilted corrected blood pressure Elevation legs Intravenous ephedrine, 30 mg. uncorrected blood pressure
Spinal
9:45
10:30 10:45 ( 31 ') 10:49 11:20
134 Spinal
10: 16 10:59 11:00 (29') 11:02 11 : 31
L.R.
I
Intra-arterial blood Pulse rate Cardiac output , pressure (mm. Hg) (Beats/min.) (Liters/min.) 1 Time Comment 9: 15 88 147/82 Elevation legs 9:29 Spinal Intravenous ephedrine, 10 mg. 9:31 79 corrected biood pressure 77/33 10:06 96 144/83
Intravenous ephedrine, 50 mg.
Spinal
uncorrected blood pressure 5:) 152
66/25 116/58 126/78
113
6.3
72 138
2.6 5.2
Spinal 38/22 60/31
Intravenous ephedrine, 50 mg. uncorrected blood pressure
Table III. Arterial and uterine venous oxygen contents and the calculated arteriovenous difference Coefficient of utilization
Blood O, {mM./L.)
A~V x
5.21 4.51
4.65 3.92
0.56 0.59
10.7 13.1
6.19 5.41 5.16
3.72
4.20 3.31
2.47 1.21 1.85
39.9 22.4 35.9
H. F. F. H.
.T . .T.
L. R.
(
A-V
A
s. s.
I
v
Patient's initials
100)
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Anesthesia for cesarean section
Table IV. Maternal blood
values~xygen
Arterial blood O, (mM./L.)
Percentage I Po: IO,saturation (mm. Hg)
Patient's initials
Capacity
H. F. F. H.
7.13 4.81
5.21 4.51
73.1 93.8
36 80
J.J.
8.32 5.83 6.04
6.19 5.41 5.16
74.4 92.8 85.4
38 70 48
S. S.
L.R.
I
57
Content
I
I I
Uterine venous blood Po: O, Content (mM./L) I 0,% Saturation 1 (mm. Hg) 65.2 4.65 32 8L5 46 3 92
I
I
24.4 36.0 27.5
44.7 72.0 54.8
3.72 4.20 3.31
Table V. Total C02 of the plasma of the arterial and uterine venous bloods, together with the pH and the calculated C0 2 tension and bicarbonate of each sample pH
Patient's initials
A
H. F. F. H.
J.J.
s. s.
L.R.
I
I
v
A
19.2 19.2
19.8 20.2
17.6 20.1 17.0
20.5 21.7 18.9
v
A
7.44 7.40
7.43 7.40
7.43 7.45 7.48
7.41 7.42 7.42
Characteristics of the umbilical arterial blood. The data on the oxygen capacity, content, and degree of oxygen saturation of the fetal bloods are presented in Table VI. The values for the oxygen capacity of bloods from the umbilical vein vary; the lowest is 6.77 and the highest 10.02 mM. per liter, and there is a tendency for the higher values to occur in the bloods of fetuses in the uncorrected hypotensive series. Correspondingly, there is a tendency for the oxygen content of the umbilical vein blood to be lower in this same group. The oxygen content of the umbilical vein bloods of the fetuses in the hypotensive series ranged from 0.94 to 3.44 mM. per liter; in the uncomplicated group the range was 3.49 to 3.98. The percentage saturation of the umbilical vein blood with oxygen averages 33.6 when the whole series of values is taken and ranges from 9.4 to 58.8 per cent. The pH of the blood in the umbilical vein varies between 7.27 and 7.40 (average 7.34) and the estimated oxygen tension from 7.2 to 23.0 mm. Hg. The average oxygen tension from the umbilical vein is 15.6 mm. Hg. When compared to the status of the mother there ap-
Pco, (mm. Hg)
HCO, (mEq./L.)
Plasma CO: (mM./L.)
I
I
v
v
A
18.4 18.3
18.9 19.2
28.0 30.7
29.3 32.0
16.8 19.2 16.3
19.5 20.7 18.1
26.3 28.7 22.7
32.0 33.0 28.7
pears to be a tendency for the tension to be lower in the uncorrected hypotensive series. The data obtained on the "total carbon dioxide" content and the C0 2 tension of the fetal bloods are presented in Table VII. The total C0 2 of the umbilical arterial blood ranges from 17.35 to 20.71 mM. per liter (average 18.49). In the plasmas the total C0 2 varied between 20.88 and 23.52 mM. per liter (average 22.11). The carbon dioxide tension in the umbilical vein blood, as calculated using the Henderson-Hasselbalch equation, ranges between 34.7 and 47.7 (average 40.8). Comment
The results presented above appear to provide for the first time data on the oxygen, carbon dioxide, and hydrogen ion concentrations of the blood entering and leaving the pregnant uterus in conjunction with similar data of umbilical vein blood in mothers who manifest severe hypotension secondary to spinal anesthesia. The circumstances that favor the increased arteriovenous oxygen differences in the uncorrected hypotensive group have not been
58
Stenger et al. \m.
St·ptt-tnh,·: 1 I~H).f. J. Oh. t. (\: ( ,YIH'C:.
Table VI. Fetal blood values-oxygen (umbilical Yein) O, (mM./L.) Patient's initials --Capa~ii-;--1---- Co~t~~t-
H. F. F. H.
6.77 7.77
:i.98 3.49
].]. S. S. L. R_
10.02 9.29 8.18
0.94 1.17 3.44
identified as yet, but we believe that they might well be attributed to a reduction in uterine blood flow-a reasonable assumption, granted the same rate of oxygen consumption of the uterus and its contents in the brief period of experimental observation. Associated with the increased A-V oxygen difference there is an increased Pco~ difference (uterine vein-maternal artery) across the uterus. As oxygen and carbon dioxide appear to move across the placental barrier by diffusion these differences in their concentrations in the uterine capillaries can be expected to affect the rate of their exchange between the two circulations-maternal and fetal. The nature of these changes in fetal blood have been shown to consist of an increased oxygen capacity, reduced oxygen content, and decreased percentage oxygen saturation. In regard to carbon dioxide we have found an increased transplacental gradient. The differences in the carbon dioxide tension in the maternal blood entering the uterus and in the arterialized blood of the fetus are shown in Table VIII. The average value in the corrected hypotensive group is 9.0 mm. Hg (range 7.0 to 11.0) . In the uncorrected the average difference is 16.5 and the range 12.0 to 19.0. It is our feeling that in the uncorrected hypotensive gravidas we have described the oxygen supply might well have been compromised-an inference which gains further support from our observations on the total osmotic pressure of the maternal and fetal plasmas of these same individuals. In the course of our observations we have noted that acute insult to the mother resulted in a rise
0, Percentage
saturation
pH
58.8
H.9
7.40 7.34
9.4 12.6 42.1
7.27 7.29 7.38
Po, (mnz. Hg)
7.2 9.5 18.1
m the total osmotic pressure of the fetal plasma with respect to the maternal ( 15 m0s./Kg./H 2 0) . When the maternal blood pressure had been corrected to prespinal levels the total osmotic pressure of the fetal plasma was slightly higher than that of the maternal (5 m0s./Kg./H 2 0). As reported by Meschia and colleagues, 1 " this measurement might well serve as a most sensitive indicator of fetal hypoxia. The physiological effects of spinal anesthesia are due solely to the preganglionic sympathetic block produced by the technique Exceptions to this statement are infrequent; hence, the cardiovascular and occasional respiratory alterations produced by this procedure cannot be ascribed to direct depression of brain stem centers by the local anesthetic. In those rare instances in which respiratory inadequacy or arrest occurs, it is more frequently due to an ischemic depression of the medullary respiratory center than due to phrenic paralysis. 13 That skeletal muscle paralysis has no effect on venous return or cardiovascular function is demonstrated by the fact that equally profound muscle relaxation produced by interference with normal myoneural junction transmission following succinylcholine administration is unattended by cardiovascular effects. At this point it is well to recall the fact that the level of sympathetic denervation extends two or as many as six spinal segments beyond the level of sensory anesthesia during spinal blockade. 14 Accordingly, it is often difficult-if not impossible-to relate sensory levels of anesthesia to physiological changes with any degree of precision. Moreover, since each preganglionic sympathetic fiber synapses
Volume 90 Number 1
in the paravertebral sympathetic chain with as many as 22 postganglionic sympathetic fibers 15 and since each postganglionic fiber is distributed to the periphery in a non-segmental manner, block of a single preganglionic sympathetic fiber during spinal anesthesia results in a peripheral sympathetic paralysis which is not only diffuse but also bears no relation to peripheral segmental sensory distribution. For these reasons the sympathetic denervation accompanying spinal anesthesia is often surprisingly extensive. In pregnant women the response to blockade might well be aggravated, for it has been shown 16 that in normal pregnancy the blood pressure is maintained mainly by neurogenic impulses. Spinal anesthesia produces arterial and arteriolar vasodilatation17 ; there results increases in pulse volume 18 and in peripheral arterial pulse wave contour. 19 The degree to which arteries and arterioles vasodilate varies in different types of tissues, and the important point to be made here is that the vasodilatation results in relatively insignificant changes in total peripheral vascular resistance. One reason for the failure of peripheral vascular resistance to decrease markedly is that compensatory vasoconstriction occurs in sympathetically intact areas. 20 Moreover, there is still resistance to peripheral flow of blood through postarteriolar vessels--the major site of resistance is shifted peripherally21 but resistance is not eliminated. Changes in total peripheral resistance during spinal anesthesia are neither as frequent nor as profound as often assumed. Severe decreases in arterial pressure, as we have noted in our study group, must be due to additional factors. Although it is impossible to make categorical statements on postarteriolar denervation, it has been demonstrated that neurogenic impulses play an ever decreasing role in vascular homeostasis as the postarteriolar bed is approached. 22 It is of critical importance, however, to recognize the fact that sympathetic nerves innervate veins and denervation is capable of producing venous hemodynamic changes. After blockade of an artery there is con-
Anesthesia for cesarean section 59
Table VII. Fetal blood and plasma valuescarbon dioxide (umbilical vein) Patient's initials
Blood (mM./L. CO,)
Plasma (mM./L. CO,)
Pco, (mm. Hg)
H. F. F. H.
18.13 17.35
22.02 23.01
35.0 41.7
J.J.
18.32 20.71 17.92
21.12 23.52 20.88
44.7 47.7 34.7
s. s.
L. R.
Table VIII. C0 2 tension (mm. Hg)
Ill
maternal artery and umbilical vein
Maternal artery
Umbilical vein
Difference umbilical vein to maternal artery
H. F. F. H.
28.0 30.7
35.0 41.7
7.0 11.0
J.J.
26.3 28.7 22.7
44.7 47.7 34.7
18.4 19.0 12.0
Patient's initials
S. S.
L.R.
siderable residual smooth muscle tone, whereas in the vein there is little or no residual tone. The degree of venodilation in denervated veins is a function of the volume of blood within the vein and, in turn, this is a function of intraluminal hydrostatic pressures determined primarily by gravity. If a sufficiently large number of denervated veins is below the level of the right auricle, the consequent peripheral pooling of blood and decrease in effective circulating blood volume have effects of greater importance in determining the physiological response to spinal anesthesia than any of the events taking place in the arterial or postarteriolar circulations because of profound effects on cardiac output. Stated in another way, the effects of preganglionic sympathetic denervation on cardiac output are determined by changes in venous return to the heart. All investigators are agreed that spinal anesthesia decreases cardiac output2 3-this statement may now be extended to the preg-
September 1. 196+
60 Stenger et al.
nant patient under clinical circumstances. The decrease is accompanied by a corresponding decrease in right auricular pressure. 24 The most important single determinant of mean aortic pressure during spinal anesthesia is cardiac output! Only when cardiac output falls is the arterial hypotension of sympathetic denervation found to be severe. In view of the relationship between venous return and cardiac output the maintenance of an adequate venous return becomes the sine qua non for the safe management of the patient with impaired activity of the sympathetic nervous system. The use of the slight head-down position, elevation of the lower extremities, tilting of the uterus to one side have all been recommended but clearly the most popular procedure is the administration of drugs which restore smooth muscle tone to denervated veins, thereby preventing peripheral pooling of blood. The concept that vasopressors raised arterial blood pressure by increasing cardiac output and/or peripheral resistance is inadequate for it is apparent that even a drug with a strongly positive inotropic effect cannot increase cardiac output and blood pressure in the presence of an inadequate venous return and an inadequate ventricular diastolic filling. Also, since the decrease in peripheral resistance during sympathetic blockade can account for on the average only 13 per cent of an observed decrease in arterial blood pressure, restoration of a pressure which has fallen 40 per cent cannot be solely the result of increased peripheral resistance. Accordingly, it is now accepted that a significant portion of the vascular response to vasopressors is due to their constricting effect on the venous circulation. There are aspects of the vasopressor situation which are disturbing to us. First, we have not been able to correct the hypotension induced in pregnant women in every instance; nor have we been successful in preventing hypotension by the use of prophylactic medication. Moya 25 also reports that of a series of 1,141 gravid patients who received ephedrine prophylactically, 46 per cent had
Am.
J.
Obst. & Gym·c.
falls in blood pressure exceeding 20 per cent of the preanesthetic level, and in more than half of the cases the systolic pressure fell below 100 mm. Hg. Second, there is recent evidence that vasoconstrictors may indeed reduce uterine blood flow. 26 Bradycardia is a characteristic finding during the sympathetic denervation of spinal anesthesia. It has been hypothesized that the slow pulse rate is due to preganglionic block of the cardiac accelerator fibers-an inadequate explanation. The primary reason is change in central venous pressure and right auricular pressures. 27 Moreover, there is a direct correlation between decrease in pulse rate and decrease in arterial blood pressurethe common denominator linking them under these conditions is, of course, venous return. Summary
The choice of anesthesia in the pregnant patient is of real significance. Indeed the unique sensitivity of the fetus to the effects, or occasional side effects, of abnost all forms of maternal anesthesia poses one of the most difficult problems in obstetrics. On the one hand, it is essential to employ an agent that will allow the safe and satisfactory execution of the technical procedures involved; on the other, it is also important to be mindful of the especial vulnerability of the respiratory center of the fetus to various anesthetics. It is well known that certain agents, whether they be inhaled or be given systemically, traverse the placenta and there rises the possibility of jeopardizing the respiratory behavior of the newborn. For other reasons also, in the recent past there has been a trend toward and widespread acceptance of conduction anesthesia for cesarean section; in this category the subarachnoid approach enjoys the greatest popularity. The purpose of this communication is not to advocate that spinal anesthesia for cesarean section be discontinued, nor is it intended to belittle the advantages of the technique. Its main aim is to point out that there are real dangers-both maternal and fetal.
Volume 90 Number 1
Anesthesia for cesarean section
61
REFERENCES
1. Stenger, V., Andersen, T., Eitzman, D., Gess· ner, I., De Padua, C., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 87: 1037, 1963. 2. Stenger, V., Eitzman, D., Andersen, T., De Padua, C., Gessner, I., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 88: 45, 1964. 3. Stenger, V., Eitzman, D., Gessner, 1., Andersen, T., De Padua, C., and Prystowsky, H.: AM. J. 0BST. & GYNEC. 87: 1042, 1963. 4. Kinsman, J, M., Moore, J. W., and Hamilton, W. F.: Am. J. Physiol. 89: 322, 1929. 5. Van Slyke, D. D., and Neill, J. M.: J. Bioi. Chern. 61: 523, 1924. 6. Prystowsky, H., and Eastman, N. J.: Bull. Johns Hopkins Hosp. 101: 45, 1957. 7. Prystowsky, H., Hellegers, A., Cotter, J., and Bruns, P.: AM. J. 0BsT. & GvNEC. 77: 585, 1959. 8. Prystowsky, H., Hellegers, A., and Bruns, P.: AM. J. 0BST. & GYNEC. 78: 489, 1959. 9. Prystowsky, H., Hellegers, A., and Bruns, P.: Obst. & Gynec. 15: 778, 1960. 10. Assali, N. S., and Prystowsky, H.: J. Clin. Invest. 29: 1367, 1950. 11. Sarnoff, S. J., and Arrowood, J. G.: Surgery 20: 150, 1946. 12. Meschia, G., Battaglia, F., and Barron, D. H.: Quart. J. Exper. Physiol. 42: 164, 1957. 13. Greene, N. M.: Physiology of Spinal Anes·
Discussion DR. S. LEON IsRAEL, Philadelphia, Pennsyl· vania. In studying the manuscript sent to me by Doctor Prystowsky several months in advance of this meeting, I was reminded constantly of the present-day facility with which scientists tell of their work as well as of the continuing difficulty experienced by others who must struggle to understand them because of a lack of easy, daily familiarity with the jargonautic ambience of such reports. In this vein, Robert Oppenheimer has recently explained that the effectiveness of the converse between specialists within a profession hinges upon problems "having to do just with communication and comprehension-understanding-of scientific knowledge." 4 For this reason, my discussion will be that of an obstetrician but of one devoted to the use of properly administered spinal anesthesia for cesarean section. Any critical references to the biochemical measurements reported by the essayists will not be those of a physiologist but rather of a clinician interpreting data with which he is not called upon to cope daily. The material presented this morning reflects Prystowsky's decade-long interest in the physiol-
14. 15. 16. 17. 18. 19. 20. 21.
22. 23. 24. 25. 26. 27.
thesia, Baltimore, 1958, Williams & Wilkins Co. Greene, N. M.: Anesthesiology 19: 45, 1958. White, J, C., Smithwick, R. H., and Simeone, F. A.: The Autonomic Nervous System, ed. 3, New York, 1952, The MacMillan Company. Assali, N. S., and Prystowsky, H.: J. Clin. Invest. 29: 1354, 1950. Lee, W. C., and Shideman, F. E.: Circulation Res. 6: 66, 1958. Neuman, C., Foster, A. D., and Rovenstine, E. A.: J. Clin. Invest. 24: 345, 1945. Eather, K. F., Peterson, L. H., and Dripps, R. D.: Anesthesiology 10: 125, 1949. Milwidsky, H., and de Vries, A.: Anesthesiology 9: 258, 1948. Haddy, F. J., and Gilbert, R. P.: Circulation Res. 4: 25, 1956. Zweifach, B. W.: Am. J. Med. 23: 684, 1957. Smith, H. W., Rovenstine, E. A., Goldring, W., Chasis, H., and Ranges, H. A.: J. Clin. Invest. 18: 319, 1939. Lynn, R. B., Sancetta, S. M., Simeone, F. A., and Scott, R. W.: Surgery 32: 195, 1952. Moya, F., and Smith, B.: J. A. M. A. 179: 609, 1962. Huckabee, W.: Personal communication. Pugh, L. G. C., and Wyndham, C. L.: Clin. Sci. 9: 189, 1950.
ogy of fetomaternal relations and his persistent effort to clarify the factors that govern the placenta's two-way transfer of gases in solution. The changing physical as well as geographic circumstances in which his investigations have been accomplished truly represent the "pursuit of knowledge under difficulties." In this study, he and his colleagues have attempted to demonstrate the effects of maternal hypotension upon the oxygen available to and used by the fetus. It is not difficult to accept the theses that the degree of hypotension following spinal anesthesia varies directly with the magnitude of sympathetic blockade; that uncorrected hypotension results in lowering of subclavian venous pressure as well as reduced cardiac output; that such physiologic alterations produce a slower blood flow within the uterus, permitting its tissues a longer period of time to extract oxygen from that blood; and that this alone eventuates in a lower oxygen content of uterine venous blood than that coming from a uterus in the absence of hypotension. The so-called "coefficient of oxygen utilization" is thus increased-a magnificent evidence of the body's physiologic economy, one
62 Stenger et al.
of its accommodating responses to maintain the all-important level of tissue oxygen in spite of reduced blood flow. Under such compensating circumstances, it is, likewise, no surprise to note the increased oxygen capacity of fetal blood. That such augmentation of the oxygen capacity of fetal blood is normal under conditions of stress was well documented by Low,:l whose investigations showed significant elevation of oxygen capacity in the fetus subjected to normal uterine contractions during vaginal delivery in contrast to that of the fetus delivered by cesarean section. Such enhancement-attributed by Born, Dawes and Mott 2 in their study of anoxia in lambs to splenic contracture and by Walker and Turnbull 5 in their investigation of umbilical cord hemoglobin levels to fetal hematopoiesis-~ probably helps to account for the astounding fact that the fetus of the markedly hypotensive patient, L. R., was able to transfer sufficient oxygen from the intervillous space to its umbilical vein. However, although we may congratulate such a fetus upon its ability to avert disaster by instantaneous accommodation, we still lack comprehension of its method. It is evident that the essayists, in their search for elucidation, are sensible to the complexity of their manifold calculations as well as of the difficulty in attaining meaningful interpretation of observations made in but five patients. They have, for instance, taken osmotic pressure as wt>IJ as pH into account. Their osmotic pressure data are of particular interest inasmuch as each of the patients received an intravenous infusion of 5 per cent solution of dextrose in watt>r continuously during the time of spinal anestht>sia. Since shifts of water in plasma can change oxygen capacity, 1 one wonders whether the hypotensively induced reduction of uterine blood flow could have also affected the fetomaternal exchange of dextrose solution and thus accounted
for the altered osmotic pressures. When maternal blood pressure was restored, the osmotic pressure of fetal plasma increased. Do('s this, perhaps, merely reflect better transfer of the administered dextrose as a result of improved uterine flow? It should be emphasized that the use of such intravenous therapy is imperative for the proper administration of spinal anesthesia for cesarean section. We have observed the drop of blood pressure to occur as late as 10 minutes after initiation of spinal anesthesia, not-as the essayists have stated-4 minutes. Because this fall rnay be drarnatic and cannot be predicted, we likewise pstablish suitable intravenous infusion
.\m.
.',q>tt'mht"'t 1. IYfi-t ,r. Ob.;r. & f;ynPc.
before the spinal anesthesia is administered; at the time of intrathecal inj1~ction of the anesthetic agent, 10 mg. of methamphetamine hydrochloride are given intravenously. If the pulse rate is above 100, we substitute 4 mg. of methoxamine hydrochloride for the methamphetamine. The intravenous route insures that the drug has entered the circulation, that its maximum effect will be produced within 5 minutes, and that the major response to it will have worn off by the time the postdelivery oxytocic is given, lessening the risk of disturbing hypertension. In our management, the danger of uncontrollable hypotension is slight. Finally, as an obstetrician, I must ask a practical question of Dr. Prystowsky, for he has tantalizingly failed to give us clinical information concerning the infant of J. J., whose umbilical vein biochemically had a literal absence of oxygen (Table VI), suggesting severe deprivation. We must not forget in our scrutiny of twigs and leaves on the many branches that a for~st has trees. Will Dr. Prystowsky please relate that baby's birth-room condition as well as its eventual neonatal outcome? REFERENCES
1. Battaglia, F.,
Prystowsky, H., Smisson, C., Hellegers, A., and Bruns, P.: Pediatrics 25: 1, 1960.
2. Born, G. \r. R., Dawes, G. S., and Mottl J. C.: ]. Physiol. 134: 149, 1956. 3. Low, ]. A.: Obst. & Gynec. 20: 363, 1962. 4,. Oppenheimer, R.: Science 142: 1143, 1963. 5. Walker, J., and Turnbull, E. P. N.: Lancet 2: 312, 1953. 807 Spruce Street Philadelphia, Pennsylvania 19107
DR. jACOB RozrER,* Winter Park, Florida. There are a few questions that come to mind. Mention of sensory level of anesthesia obtained is not recorded, but it is pointed out that the sympathetic level of anesthesia does run much higher than the sensory level. Moya 1 reported that 46 per cent of cesarean sections with spinal anesthesia exhibited a greater than 20 per cent fall in blood pressure. Moya also pointed out that pressure of the uterus on the vena cava is probably responsible for the lowered cardiac output and hypotension in I 2 per cent of cases in which tht> blood pressure falls below 100 mm. Hg systolic. Hingson 2 likewise stated that uterine pressure on the vena cava is a probable cause of hypo-
*By invitation.
Volume 90 Number 1
tension and further stated that profound hypotension is twice as frequent in anemic patients. I would assume that anemia was not a factor in the case studied. It would have been interesting to have had continuous fetal electrocardiographs since Hon 3 states that the fetal heart shows definite pathologic bradycardia of a hypoxic type within a few minutes after the maternal blood pressure drops below 100 mm. Hg systolic. In review of the cesarean sections done during the last years under spinal anesthesia at the Winter Park Hospital where all spinals were given by trained anesthesiologists there seems to have been little hypotension. Thirty-two per cent of patients showed a fall of 15 per cent in blood pressure but 3 per cent dropped below 100 mm. Hg systolic. All live born babies had an Apgar score of 8 to 10. One stillborn infant resulted from complete abruptio placentae. It is
Anesthesia for cesarean section
63
not the policy of the anesthesiologist to give a preoperative prophylactic vasopressor. We have certainly not been presented with such problems of hypotension as the essayist describes for, otherwise, I would be looking for another and safer type of anesthesia. The preoperative maternal arterial oxygen saturation, not given in this paper, would have been interesting to know for comparison with the oxygen saturations during hypotension, commenting upon which the authors state that "we are unable to explain this wide variation in the degree of arterial saturation." REFERENCES
1. Moya, F., and Smith, B.: J. A. M. A. 179: 609, 1962. 2. Hingson, R. T., and Cull, W. A.: Clin. Obst. & Gynec. 4: 104, 1961. 3. Hon, E. H., and Chung, F.: Obst. & Gynec. 13: 633, 1959.