Epidural analgesia for obstetrics

OBSTETRICS

Epidural analgesia for obstetrics A maternal,

fetal,

and neonatal

JOHN

S.

MCDONALD,

M.D.

LARS

L.

BJORKMAN,

M.D.

ENRIQUE

C.

Los Angeles,

REED,

study

M.D.

California

The effect of lumbar epidural (LE) and caudal epidural (CE) analgesia on the fetal heart rate and fetal acid-base status (pH and base excess) of 41 patients was studied during first- and second-stage analgesia in a controlled research delivery room environment. All patients had baseline parameters which made it possible to observe the effects of the epidural technique upon the fetal heart rate, pH, and base excess. Certain neonatal parameters were recorded to evaluate the epidural effect upon the neonate’s postdelivery period. These included Apgar scores at 1 and 5 minutes, umbilical cord arterial and venous blood gases, and neonatal blood gases from the umbilical artery in the first hour after birth. There was an increase in late deceleration after epidural block despite segmental analgesia with minimal lidocaine dosages and the absence of hypotension. However, unless second-stage embarrassment or hypotension occurred, no significant deterioration of the acid-base status was noted. The greatest incidence of late deceleration was noted when epidural analgesia was combined with oxytocin. For the few toxemia patients studied, the epidural technique did not prove hazardous. These intrapartum regional analgesic techniques (LE and CE) do not appear to present a hazard to the normal fetus or the fetus at mild risk. Nevertheless, discretion would dictate that these techniques be restricted with evidence of combined antepartum and intrapartum fetal compromise.

THIS ARTICLE iS the result of a 2 year study which was conceived to determine whether an increase in late decelera-

tion or fall in pH occurred after epidural analgesia. It was prompted by recent clinical studies which raised the query of fetal hazard secondary to the popular epidural technique. l, 2 Our clinical impression, based on a large obstetric regional anesthesia service, had already confirmed the opinion of Bonica and others who suggested that neonatal condition was optimal with major regional techniques after minimal drug exposure and eradication of the hypotensive hazard.:‘, 6 Original fetal heart rate interpretations by Hon an8 Quilligan6 were devised exclusive

From the Department of Obstetrics and Gynecology, Women’s Hospital, Los Angeles County/University of Southern California Medical Center. j$;;ived Revised Accepted

for publication April April

January

17,

8, 1974. 26,1974.

Reprint requests: John M.D., P.O. Box 54508, California 90054.

S. McDonald, Los Angeles, 1055

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VD+LD

A

LD

LD

A

VD+LD J w

FHR ------------

----------,A % PATHOLOGICAL

----

-

PATTERNS

15, 1974 Gynecol.

-------__---__--

f

% PATHOLOGICAL

PATTERNS

UTERINE \ CONTRACTIONS

FETAL

pM. BE

FETAL

pH. BE

Fig. 1. Model

FHR-acid-base study. The frequency of late decelerations (number of late decelerations vs. all patterns) prior to activation of the epidural was noted and compared to the frequency afterward. Usually the time was 30 minutes on each side of activation. In addition, pH and base-excess baselines were established before activation within 60 minutes and from 15 to 60 minutes afterward. VD, variable deceleration; LD, late deceleration; A, acceleration.

Table I. Maternal

1 Normal Toxemia Diabetes Premature Others

class A-D rupture

Table II. Analgesia

and fetal complications

of the membranes

17 13 7 5 12

of specific analgesic considerations. The techniques of both fetal heart rate monitoring and fetal pH sampling have unquestionably improved intrapartum fetal surveillance.7-11 These techniques have improved both obstetric and anesthesiologic management and have made it possible to investigate the effects of epidural analgesia on the mother and the fetus. To our knowledge, this is the first combined fetal heart rate and pH study specifically related to the epidural analgesic technique performed in a controlled optimum environment.* Material

and

methods

The optimum environment consisted of a single labor and delivery room dedicated to *The authors are appreciative Section of Perinatal Biology and

of the cooperation E. H. Hon, M.D.

1

No.

of the

Good Fair Poor Total

effectiveness E~idurals 35 5 1

1

Per cent 85.5 12 2.5

41

a complete 6 to 8 hour intrapartum study with staff personnel including two obstetricians (one fellow and one staff consultant), one pediatrician, two anesthesiologists (one fellow and one staff consultant), and three nurses. Some of these personnel were in constant attendance. Instrumentation included a seven-channel Brush Clevite Mark 200 paper recorder and an Ampex FR-1260 magnetic tape recorder for preservation of continuous fetal heart rate (FHR) , maternal heart rate (MHR) , fetal beat-to-beat interval, maternal uterine pressure, fetal electrocardiogram (FECG) , maternal electrocardiogram (ME and maternal blood pressure. Fetal CG), heart rate and beat-to-beat interval were detected by a scalp electrode. Maternal heart rate was recorded from the MECG by standard chest leads. Uterine pressure was perceived by use of an intrauterine cathe-

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ter connected to a Statham transducer. Maternal blood pressure was detected by the Doppler ultrasonic technique. Forty-one patients with continuous heart rate monitoring and intermittent fetal pH measurement had either lumbar (29) or both ( 12 ) lumbar and caudal epidural catheters inserted. The lumbar epidural technique consisted of the paramedian approach described by Bonica,“’ using lack of resistance for epidural space identification and insertion of the catheter tip between the twelfth thoracic and the first lumbar vertebrae. Caudal catheter placement consisted of the usual sacrococcygeal puncture with catheter tip location between the first and second sacral vertebrae in order to decrease the required total volume of local anesthetic. All patients had certain baseline parameters which allowed a comparison of fetal heart rate and fetal pH base excess changes. These parameters included: ( 1) the continuous recording of the fetal heart rate for ,t fixed interval before and after activation; the interval prior to epidural injection was 30 minutes, the interval after was 30 minutes in 31 patients and 20 minutes in the remainder; (2) fetal scalp pH’s and base excesses with multiple punctures within 60 minutes prior to and 15 to 60 minutes after activation. Epidural injection was performed sometime during the acceleration phase of labor (after cervical dilatation of 4 cm. or more) .I” The drug was lidocaine without epinephrine (1 to 2 per cent) in a dosage depending upon the first- or second-stage need. Of the 41 patients, 29 had 60 to 120 mg. and 12 had 150 to 200 mg. For first-stage pain relief, a T-10 to L-l band of analgesia, from the tenth thoracic to the first lumbar vertebrae, with 60 to 120 mg. was used. For second-stage relief, perineal analgesia was instituted with a larger dose of 200 mg.14 All epidural injections were monitored in the standard fashion of detecting changes in blood pressure and noting the 30 minute analgesic level by identifying involved dermatomes. A systolic or diastolic reduction of at least 20 mm. Hg was defined as significant

Epidural

INCREASE

analgesia

DECREASE

1057

NONE

LATE DECELERATION

Fig. 2. The

per cent of patients who experienced a change in the incidence of late deceleration after epidural. Group A (56 per cent), 23 patients with increased late decelerations, and Group B (22 per cent), nine patients with no change in the frequency of late decelerations, are compared to Group C (22 per cent), nine patients with no late deceleration patterns recorded at any time.

and immediately treated with left uterine displacement, leg elevation, and intravenous fluid administration, After the onset of analgesia, another fetal pH base excess was determined. If delivery occurred within 60 minutes of epidural injection and a fetal pH was not obtained, umbilical artery values were used to reflect postinjection fetal pH and base excess since fetal scalp values and umbilical artery values have been shown to correlate closely.15 Neonatal data consisted of the Apgar scores at 1 and 5 minutes, umbilical cord arterial and venous blood gases, and umbilical artery neonatal blood gases in the first hour. All aforementioned parameters were continuous except maternal, fetal, and neonatal blood gases and maternal blood pressure, which were detected at predetermined times.

Fetal

blood

gases

were

taken

con-

comitantly with maternal samples and additionally during fetal heart rate changes. Neonatal blood gases were sampled at approximately 8, 16, 32, and 64 minutes of life. Maternal blood pressure was recorded

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c

‘7.38,

7.34.

T ‘..\\ 1

7.30.

7.26. PH 7.22,

. . . . .

T 1

‘e

7.18.

7.14, N: 23

N=9

N=9

7.10.

:

I I

I II

Fig. 3. The pH value (mean and standard deviation) before (Z) and after (II) activation in patients from Groups, A, B, and C as described in Fig. 2. every 2 minutes after epidural activation for 20 minutes and thereafter every 5 minutes. A summary of the method of study is graphically depicted in Fig. 1. All statistical analyses were performed by first determining the nature of the population, e.g., normal or not normal. The population was analyzed by probits or rankits for normalcy. All subsequent analyses were performed with the appropriate statistics, e.g., parametric method for normal distribution and nonparametric method for nonnormal distribution. Results Table I details the various maternal and fetal complications. The category “Others” included prematurity, Rh sensitization, and meconium staining. The distribution of parity was para 0, 25; para 1, 12; para 2 or more, 15. There were no breech, twin, or cesarean section deliveries in the study. Table II outlines the analgesic results. Analgesia categories were defined as follows: Good, no sensation or pressure only with contractions or episiotomy; fair, some burning sensation

epidural

with episiotomy and moderate discomfort during a contraction in the face of a detectable sensory level; poor, lack of analgesia for contractions and episiotomy in the face of no detectable sensory level. Pathologic patterns were defined as all late decelerations in a fraction of the whole both before and after lidocaine injection. Thus, pathologic patterns may vary from the preto postlidocaine period 100 per cent. For example, two pathologic patterns out of 10 total contractions in the 30 minutes before lidocaine injection (20 per cent) but four pathologic patterns out of 10 total contractions in the 30 minutes afterward (40 per cent) would equal a net increase of 20 per cent for the study period (40 minus 20 = 20 per cent). In 41 fetuses, 23 experienced an increase in the number of late decelerations after epidural injection (Group A), nine had a decrease or no change in these patterns (Group B) , and another nine had no pathologic patterns before or after activation (Group C) (Fig. 2). The mean increase in late deceleration in Group A was 21.6

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Fig. 4. Baseline (I) and activation (II) pH and base-excess values (mean and standard deviation) were recorded at various stages of cervical dilatation. Group 1 (13 patients), between 4 and 5 cm.; Group 2 ( 18 patients), between 6 and 8 cm.; Group 3 ( 12 patients), at complete dilatation.

per cent compared to a median of 20.0. The 95 per cent confidence range was between 3.0 and 55.0 per cent. The pH values of the same fetuses just described were examined to see if significant changes in pH occurred in the group experiencing an increased incidence of late deceleration after epidural. Values for pH in Group A, with an increased incidence of late deceleration, Group B, with a decreased incidence or no change, and Group C, those with no pathologic patterns, are compared in Fig. 3. Since the group with no patterns (C) had a baseline pH of 7.31 with a fall to 7.27 and a standard deviation of + 0.05, the definition of a significant fall from baseline became 0.09, i.e., the mean plus one standard deviation. There were three fetuses with a significant pH fall in Group A, i.e., pH reductions greater than 0.09 U. A rank correlation test,

. used to determine if there was an over-all relationship between pH’s and FHR changes in the three groups, was not significant (r = 0.08). Both pH and base-excess changes associated with different stages of labor are summarized in Fig. 4. Except for those patients who were activated near second stage, there does not appear to be a significant fall in pH or rise in base deficit. Because of other problems associated with the second stage, such as an increased incidence of occult cord problems, Valsalva efforts of the mother and prolonged falls in the heart rate secondary to pressure on the fetal head, it would be improper to presume that a pH fall during the second stage was related solely to the anesthetic technique. The dosage of oxytocin was not increased before or after the epidural activation, The

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_ -

-10

0

10

20

Tim

Fig. 5. The stimulation

Table III.

mean frequency per 5 minute

Umbilical

Umbilical Arterial Venous

cord

of contraction period.

cord blood

30

_

OXYTOCIN NO OXYTOCIN

50

40

15. 1974 Gynecol.

60

(MINUTESI

before

and

after

epidural

with

and

without

oxytocin

gases (N = 39)

fifJ 7.22 (* 0.08) 7.30 (r 0.07)

frequency and amplitude of uterine contractions after epidural injection were not increased; in fact, Fig. 5 demonstrates that the contraction frequency is essentially the same with or without oxytocin. This would rule against hyperstimulation as a possible contributory cause of the increased frequency of abnormal heart rate patterns. Time relationships of late deceleration patterns which occurred after epidural injection with and without oxytocin stimulation are displayed in Fig. 6. The arbitrary two groups, representing those who had < 150 mg. and > 150 mg. of lidocaine, were found to be of the same population (p > 0.1, Mann-Whitney U.). Therefore, in our series, the mean increase in late deceleration after lumbar epidural was independent of the dosage between 60 and 200 mg. In 13 patients with the diagnosis of toxemia, there were only four patients who had an increase in late deceleration after lumbar epidural injection. The increase was from 3.1 to 31.9 per cent. In addition, pH and base-excess abnormalities were not striking and less than for the group as a whole.

Pot 19 (’

B.E.

Pco, 4)

28 (” 6)

49

(t

9)

39 (2 7)

-10

(5 3)

-8 (* 3)

The mean neonatal Apgar score for the toxemia patients were 8 and 9 at 1 and 5 minutes, respectively. The general distribution of Apgar scores at 1 minute revealed that six neonates had scores of 6 or less and 35 had scores of 7 or more. At 5 minutes only three neonates had scores of less than 7 and 38 had scores of 7 or greater. Three of the 23 neonates with an increase in pathologic patterns after lidocaine had low 1 minute Apgar scores, but all had good transition of scores from the 1 minute to the 5 minute period. Three of the 12 fetuses with improved patterns after activation had low 1 minute Apgar scores. These fetuses, however, had a proportionately greater degree of acidosis in utero and a greater incidence of abnormal heartrate patterns established during the baseline. Interestingly, two of the three neonates with scores lower than 7 at 5 minutes showed increased pH and decreased frequency of pathologic fetal heart rate patterns following epidural activation (Fig. 7). Umbilical cord arterial and venous blood gas values with means and standard deviations are shown in Table III. Neonatal ar-

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1 \ \ \ \ .---.

-0XYTOClN _

-10

0

10

EIlDlJRAL

Fig. 6. After both epidural activation distribution of late deceleration which

20 TIME

30

40

-NO

OXYTOCIN

50

(MINIJTESJ

and oxytocin stimulation, increases at 10 minutes

terial blood gas transitions at four time periods over the first hour are illustrated in Fig. 8. Baseline maternal blood pressures ranged from 160 to 100 mm. Hg systolic and 100 to 70 diastolic. A significant fall in blood pressure was -recorded as 20 per cent reduction in systolic. Only one of the 41 patients experienced such a reduction. The involved fetus had both an increase in pathologic patterns after epidural injection (14 ner cent) and a concomitant fall in pH (7.33 before and 7.2% after).

there is an interesting frequency and plateaus until 30 minutes.

10

9

x % 2 a

8

I 0

%

‘i’0

I 0

7 FIVE

MINUTE

ONE MINUTE

Comment In 18 of the 41 cases there was either no change or a decrease in late decelerations after epidural. Twenty three of the 41 recordings revealed an increase in late deceleration after epidural injection. This should be disconcerting, since this pattern has been linked with fetal acidosis and recently Kubli l6 has corroborated that repetitive, severe late decelerations were associated with subnormal fetal pH values. Yet, in this study only three of the 23 fetuses with increased late decelerations after epidural

A

B

C

Fig. 7. Mean Apgar values with 1 to 5 minute transitions for Group A with an increased frequency of late decelerations, Group B with no change in the frequency, and Group C with no patterns.

injection experienced significant pH changes (Fig. 3). One of these three has an explanation for the decline in pH. This was the only patient who had a baseline pH of 7.20 and a value of 7.18 just 6 minutes prior to delivery but a subsequent umbilical artery value of 7.01. There were three loops of cord

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50

40

7.18

30

20 8

16 32 MINUTES

64

8’ MINUTES

-16

76

BE

-8

PO2

52

.

8

Fig. 8. Four parameters, graphically presented within the first hour

16 32 MINUTES

pH, to illustrate of life.

8)

8

B.E., and PO,, with mean and the ability of the neonates to achieve

Pco,,

about the neck of this fetus, which may have caused circulatory embarrassment. Nevertheless, the value of 7.01 was included because of adherence to previously outlined criteria of no pH sooner than 15 minutes after epidural injection. The second fetus had a fall in pH of 0.09 U. with no explanation other than an association with Group A (increased late decelerations after epidural injection). The third fetus was the only one of the entire group of 41 patients subjected to an episode of maternal hypotension after epidural injection. One explanation for a significant pH decline rarely accompanying late deceleration in this study may be that the latter were of a mild type, defined as less than a 15 beat per minute fall in heart rate from the baseline. In addition, they were not repetitive for any length of time. Previous investigators have documented individually the changes in pH or heart rate associated with labor.17-lg The first correlative study between fetal heart rate and fetal pH concluded that, although there was a remarkable correlation between different fetal

I

16 MINUTES

standard normal

.

.

32

64

deviations, are blood-gas values

heart-rate patterns and fetal pH, there was a wide range of pH values with considerable overlapping. I8 Furthermore, that study graphically illustrated that there was a much greater tendency for pH values in severe late deceleration to be less than pH 7.25, whereas the grouping in moderate and mild patterns displayed values on both the high and low sides of pH 7.25. In one recent study, late decelerations were associated with epidural analgesia.2 In that report there are several points to consider in regard to the technique of regional analgesia for obstetrics. First, there was no distinction made between the lumbar epidural and the caudal epidural techniques. The latter-caudal-is associated with at least twice the volume of local anesthetic to effect similar first-stage analgesia. Second, there was no dosage standardization of local anesthetic for either the epidural or the caudal techniques. Third, there was no attempt to limit regional analgesia for first stage to the lower thoracic and upper lumbar dermatomes. Last, but not least, no

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Fig. 9. This figure reveals hypotension after epidural activation and ,a fall in heart rate. The upper tracing (A and B) is the fetal heart rate which is quite %oisy” due to electrical interference. The lower tracing (A and B) is uterine pressure and shows periodic contractions and relaxation. At 17: 34, 12 C.C. of 1.5 per cent lidocaine was injected into the epidural space. Seven minutes later, in panel B, just before 17 : 41, the fetal heart rate descended from 120 to 60 beats per minute. The patient had denervation of segments T-8 to S-4. Maternal hypotension is recorded as 90/60 (with a baseline of 140/80, panel A). Various therapeutic measures were instituted including fluids, oxygen, and ephedrine. Shortly thereafter, the blood pressure was recorded as 130/70 and the fetal heart rate returned to 120.

group treated with other analgesic methods was offered as a comparison. Thus, the association of late deceleration to epidural analgesia could have been due to inadequate technique or purely accidental and simply reflective of maternal complications. Nevertheless, it does nicely demonstrate one method of obstetric anesthesia where oxytocin induction and stimulation may play a complementary role in obstetric management of the intrapartum period. Fig. 9 illustrates what bad effects multiple-segment epidural injections may have when associated with hypotension. The patient’s level was subsequently recorded as involvement of the eighth thoracic to the fourth sacral segments. Seven minutes after activation of this patient, bradycardia occurred and persisted for 10 minutes. As noted in the figure commentary, various therapeutic measures were instituted. The prolonged heart rate deceleration might have been averted if immediate therapy had been instituted at the earliest sign of a reduction in blood pressure. This technique illustrates less than

optimal regional obstetric analgesia as would be currently defined by such criteria as segmental tenth thoracic to second lumbar first-stage analgesia and immediate identification and treatment of hypotension. The frequency distribution of late deceleration patterns after epidural activation presents some rather interesting features. Fig. 6 demonstrates a tendency of late decelerations to occur between 10 and 40 minutes after activation. This timing may be correlated with the onset of the maternal sympathetic block with unrecognized placental insufficiency or the time of maximum local anesthetic level after epidural injection.20-22 Fox and associates5 reported fetal and maternal lidocaine levels at 20 minutes after injection. Their dosage for lumbar epidural analgesia (50 to 60 mg.) resulted in fetal levels no greater than 0.5 pg per cubic centimeter. Large amounts of fetal myocardial exposure to lidocaine may be sufficient to elicit deletorious mechanical and electrical effects. Myocardial exposure equals the concentration of drug times the blood flow and

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fetal blood flow is approximately three times as great per gram of tissue as that of the mother. Therefore, a negative mechanical effect could be a reduction in contractile force. A negative electrical influence could involve the effect of lidocaine on cardiac electrical activity. Sugimoto and associates23 revealed that local anesthetics prolong the P-R interval and Lieberman and associates2” demonstrated that P-R interval prolongation was directly related to lidocaine dosage. Neonatal acid-base values summarized in Fig. 8 reflect the vitality of these neonates who developed a normal acid-base balance well within the first hour of life. Their ability to accomplish this, of course, is partially dependent upon a nondepressed respiratory center and adequate alveolar ventilation to generate optimal Paoz and Paooz values. In this report we have observed fetal heart-rate responses and acid-base changes after lumbar epidural (LE) for the first stage of labor and LE or caudal epidural (CE) for the second stage. It should be made clear that the authors do not believe any one anesthetic technique or agent is optimal for all intrapartum pain relief. Epidural analgesia has long been popular as both a firstand second-stage technique by those anesthesiologists and obstetricians who have taken the time to master its technical aspects. It has been the intent of this paper to objectively evaluate the epidural in a carefully controlled and monitored group of obstetric patients. There are several points of significance: 1. In 41 patients, only 23 revealed an increase in the per cent of late deceleration patterns following the lumbar (LE) or caudal (CE) epidural technique utilizing lidocaine. This occurred despite the absence of hypotension and use of minimal effective dosages of lidocaine. 2. Unless hypotension or an embarrassment of second-stage mechanics occurred, no significant fall in pH or rise in base deficit was noted.

REFERENCES

1. Zilianti, M., Salazar, J. R., Aller, J., and Aguero, 0.: Obstet. Gynecol. 36: 881, 1970.

December Am. J. Obstet.

15, 1974 Gynecol.

3. The timing of the development of late deceleration was consistently between 10 and 40 minutes after epidural activation. 4. For 13 toxemic patients, the epidural technique did not prove to be hazardous to the fetus. These patients experienced only a minimal fall in pH and rise in base deficit and, in fact, compared very favorably to the remainder of the group. It is difficult to explain this except for the possibility of a visceral sympathetic block which may suppress uterine alpha-adrenergic influences.*5g 26 Epidural analgesia has heretofore withstood the clinical test of time. This study confirmed that serious intrauterine asphyxia does not follow epidural analgesia despite an increase in mild late deceleration. Nevertheless, we would still be generous in restricting regional analgesia when both abnormal fetal heart-rate parameters are present (i.e., a flat fetal heart rate with poor variation on the baseline and late deceleration of a moderate or severe nature) and antepartum parameters reveal placental insufficiency (i.e., low estriol values and positive oxytocin challenge) .27, 28 The epidural technique may be contrasted to paracervical block where fetal acidosis may occur if bradycardia lasts longer than 10 minutes.“s Admonitions to restrict paracervical block for high-risk obstetric patients already exists. 31a32 Such an admonition cannot be presently made for the epidural technique. Admittedly, our limited number of 41 patients who might have exhibited placental insufficiency is modest. Nevertheless, another larger clinical study is now under way to shed further light on the role of epidural analgesia in certain highrisk obstetric patients. We are appreciative of the help of John J. Bonica, M.D., and Edward J. Quilligan, M.D. for manuscript suggestions, Robert M. Nakamura, Ph.D., for statistical analysis, and Arlene Rogers for manuscript preparation.

2. Schifrin, B. 8: J. Obstet. Gynaecol. Br. Commonw. 79: 332, 1972. 3. Bonica, J. J.: Principles and Practice of

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4. 5.

10. 11. 12.

13.

14.

15. 16.

17. 18.

19.

Obstetric Analgesia and Anesthesia, Philadelphia, 1967, F. A. Davis Company, chap. 36, vol. 1. McDonald, J. S.: Int. Anesthesiol. Clin. 1972. Fox, G. S., Home, G. L., Desjardins, P. D., and Mercier, G.: AM. J. OBSTET. GYNECOL. 110: 896, 1971. Hon, E. H., and Quilligan, E. J.: Conn. Med. 31: 779, 1967. Hon, E. H., and Quilligan, E. J.: Clin. Obstet. Gynecol. 11: 145, 1968. Saling, E., and Schneider, D.: J. Obstet. Gvnaecol. Br. Commonw. 74: 799. 1967. Mender-Bauer, C., Arm, I. C., ’ Gulin, L., Escarcena, L., and Caldeyro-Barcia, R.: AM. J. OBSTET. GYNECOL. 97: 530, 1967. Hollmen, A., Jagerhorn, M., and Pystynen, P.: Acta Anaesthesiol. Stand. 11: 341, 1967. Peel, J.: Proc. R. Sot. Med. 61: 32, 1968. Bonica, J. J.: Principles and Practice of Obstetric Analgesia and Anesthesia, Philadelphia, 1967. F. A. Davis Company, chap. 35, vol. 1. Hendricks, C. H., Brenner, W. E., and Kraus, G.: AM. J. OBSTET. GYNECOL. 106: 1065, 1970. McDonald, J. S.: In Current Obstetrics and Gynecology, Diagnosis and Treatment, 1974, Lange Medical Pub. Bretscher, J., and Saling, E.: AM. J. OBSTET. GYNECOL. 97: 906, 1967. Kubli, F. W.: Proceedings of the Third European Congress of Perinatal Medicine, Lausanne, Switzerland, 1972. Quilligan, E. J., Katigbak, E., and Hofschild, J.: AM. J. OBSTET.GYNECOL.QI: 1123,1965. Kubli, F. W., Hon, E. H., Khazin, A. F., and Takemura, H.: AM. J. OBSTET. GYNECOL. 104: 1190, 1969. Wood, C., Newman, W., Lumley, J., and

Hammond,

J.:

AM.

J.

OBSTET.

GYNECOL.

105: 942, 1969. 20. Morishima, 21. 22. 23.

24. 25. 26. 27.

H. O., Davies, S. S., Finster, M., Poppers, P. J., and James, L. S.: Anaesthesia 27: 147, 1966. Lurie, A. O., and Weiss, J. B.: AM. J. OBSTET. GYNECOL. 106: 850, 1970. Bromage, P. R., and Robson, J. G.: .4naesthesia 16: 461, 1961. Sugimoto, T., Schaal, S., Dunn, N., and Wallace, A.: J. Pharmacol. Exp. Ther. 166: 146, I969. Lieberman, N. A., et al.: Am. J. Cardiol. 22: 375, 1968. Boba, A., Linkie, D., and Plotz, E. J.: Obstet. Gynecol. 37: 247, 1971. Greiss, F. C.: AM. J. OBSTET. GYNETOL. 111: 611, 1971. Goebelsmann, U., Freeman, R. K., Mestman, J. H., Nakamura, R. M., and Woodling, B. A.: AM. J. OBSTET. GYNECOL. 115: 795,

1973. 28.

29.

30. 31.

32.

Freeman, R. K.: In Moghissi, K. S., editor: The Placenta, Biological and Clinical Aspects, Springfield, Ill., 1974, Charles C Thomas, Publisher. Freeman, R. K., Gutierrez, N. A., Ray, M. L., Stovall, D., Paul, R. H., and Hon. E. H.: AM. J. OBSTET. GYNECOL. 113: 583, 1972. Gordon, H. R. : N. Engl. J. Med. 279: 910, 1968. Westholm, H., Magno, R., and A-Son Berg, A.: Acta Obstet. Gynecol. Stand. 49: 335, 1970. Caldeyro-Barcia, R., Mendez-Batter, C., Posiero, J. J., Escarcena, L. A., Pose, S. V., and Bieniarz, J.: In Cassels, D. E., editor: The Heart and Circulation in the Newborn and Infant, New York, 1966, Grune & Stratton, Inc., pp. 7-36.

1 Attention

to authors:

Change

in

Reference

Style

The Editors and Publisher have agreed to add the article title to references in the AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY. References will now conform to the style of the Cumulated Index Medicus, viz., name of author, title of article, name of periodical, volume, page, and year. Authors are always encouraged to limit references to sixteen tot- the following journal sections: Obstetrics, Gynecology, and Fetus, Placenta, and Newborn.