Analgesia in obstetrics

Analgesia in obstetrics The effect of analgesia

WILLIAM

W.

WARNER NAOMI Elmhurst,

C. W. brew

on uterine

FILLER, HALL.

FILLER,

JR.,

contractility

and fetal

heart

rate

M.D.

M.D. M..4

York

The problem of finding e$ectit*e pain relief for the patient 6n labor, without hindering the progress of inbor or harming the fetus, ha, been a much explored and discussed endeavor of obstetricians for many years. Using the methods of Caldeyro-Barcia, Alvarez, and Pantle, 64 patients were carefully studied using pentatocine, meperidine, caudal block, and saddle block analgesia. The effect of these analgesic agents on labor and fetal heart rate were analy:ed. All analgesia except the caudal methods increased uterine contractility. Only saddle block had a significant effect on fetal heart rate. Using these data and others gleaned from the literature, a hypothesis concerning the role of epinephrine and of the autonomic newous system in the control of uterine contractility is discussed.

F o R M A N Y years it had been universally taught that administration o,f the commonly used analgesic agents retarded the progress of labor. It was, therefore, advised that these agents should not be administered until labor was active and progress was rapid. In the last 15 years more scientific analysis of the progress of laborI and accurate recording of uterine contractility’ revealed that this classical teaching was inaccurate. The administration of analgesic drugs has been shown to contribute to newborn respiratory depression if gi\-en injudiciously. Too high a dosage or improper timing of the administration of analgesia will depress the central nervous system of the newborn with consequent respiratory embarrassment. Ncwer techniques for the diagnosis of fetal distress, such as electronic recording of the

fetal heart rate”, I89 I93 “-I, 2c and the measurement of the pH of fetal blood samples,‘l, “? have led to more accurate diagnosis of this condition and better estimates of newborn prognosis. The effect of the respiratory depression produced by analgesia, however, is not ascertained by these newer methods of diagnosing fetal distress, because the fetal respiratory processes are not of importance until after birth. The authors have done simultaneous recordings of uterine contractility and fetal heart rate for 5 years. The recordings selected for presentation here are those cases in which the effects of various methods or alleviating pain have been analyzed as to any changes produced on uterine contractions or fetal heart rate. It is felt that this evidence taken together with the excellent work of numerous other investigators over the last 15 years will shed some light on this problem.

From the Department of Obstetrics and Gynecology, New York University School of Medicine, and the Obstetrical and Gynecological Service (Third Surgical Division) Belleuue Hospital. Present address: The Mount Sinai Hospital Services, City Hos$ital Center at Elmhurst. 79-01 Broadway, Elmhur.rt. New York 11373.

Materials

and

methods

The results reported in this paper were selected from 64 pregnant patients whost: uterine contractions and fetal heart rate 832

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were recorded simultaneously using the methods of Alvarez and Caldeyro-Barcia” and Pantle.‘” All of the 64 patients were at or near term. All patients were delivered of termsized infants during or shortly after the recording period. Sixty-one of the deliveries were vaginal; 3 deliveries were by cesarean section, 2 for fetopelvic disproportion and 1 for prolapse of the umbilical cord. All infants were live-born and discharged in good condition from the nursery after a routine stay. There were 28 primigravidas and 36 multiparas. There were 3 patients with preeclampsia, 2 of mild and 1 of moderate severity. These were the only patients exhibiting any significant complication of pregnancy. In each group studied there was a random distribution of cases with ruptured or intact membranes during the period of study. Cervical dilatation varied from 2 to 8 cm., with an average of 5 cm. during the recording period. There were 3 breech presentations; the remainder were vertex. The station of the presenting part varied from -3 to +3, and in most cases was about 0 station except for the group who received saddle block anesthesia. In this group the average station was +2. Fifty patients were in spontaneous labor. Nine were receiving oxytocin infusions and 5 received intramuscular sparteine sulfate, Six received caudal analgesia using 150 mg. of lidocaine. Eight of the patients were given saddle bIock anesthesia with 5 mg. of tetracaine in a hyperbaric solution. Twentyfive patients received intramuscular or intra\.enous administration of pentazocine, 25 patients received intramuscular or intravenous administration of meperidine hydrochloride. Analysis of the recordings showed that the route of administration of the analgesic drugs did not affect the changes in uterine contractility seen with these drugs. The only factors affected by the route of administration were the time of onset and duration of the analgesic effect. The changes in uterine contractility were seen when satisfactory analgesia was established no matter how the drug had been administered. The dosage of

Analgesia

in obstetrics

833

pentazocine varied from 30 to 45 mg. The dosage of meperidine varied from 75 to 100 -57. The maternal blood pressure was followed in all cases. All patients were kept in a supine position during the entire study period, except for the brief period in which the position was changed in order to administer the saddle and caudal blocks. During the recording, the intensity, frequency, tone, and uterine activity of each The avera
The results of this study are analyzed in six separate parameter-s. First, the effect of pentazocine on uterine contractility, which is measured by its effect on over-all uterine activity, intensity, frequency, and tone. Second is the effect of meperidine; third, the effect of saddle block; and fourth, the effect of caudal block on uterine contractility measured in the same manner. The fifth is the effect, if any, of all these analgesic methods on fetal heart rate. All these above param-

834

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Hall,

and

July Ii, 1467 .Am. J. Obst. & (;ynw.

Filler

DILATATION 7 cm I

UTERINE

ACTIVITY

INTENSITY

TONE

UNITS)

134.24

(m m/Hg)

FREQUENCY

A

(MONTEVIDEO

21.14

(CONTRACTIONS/IO

MINUTES)

6.415 8.18

(mm/Hg)

DILATATION 9 cm I

UTERINE ACTIVITY

(mm/Hg)

TIME

FETAL HEART

(beats/mm)

UTERINE

ACTIVITY

INTENSITY

B

UNITS)

(mm/H@

FREQUENCY TONE

(t40NTt31DE0

(CONTRACTIONS/IO

211 20 34.32

MINUTES)

6 319

(mm/H@

Fig. 1. A, Control period, before injection of pentazocine. The bottom recording illustrates a simultaneous continuous recording of the fetal heart rate which remained unchanged in 40 mg. intravenously, showing obvious all cases. B, Period after injection of pentazocine, effect on restlessness and contractions within 3 minutes.

Volmne Nrmber

98 6

Analgesia

eters were analyzed in the 50 patients in spontaneous labor. The sixth parameter analyzes the effect of the administration of meperidine on patients whose labor was either stimulated or induced using an oxytocin intravenous infusion or sparteine sulfate \given intramuscularly. Effect of pentazocine on contractility.1” In 21 patients, uterine activity was increased after the administration of pentazocine by an average of 36.1 Montevideo units. In 1 case there was a decrease in uterine activity

in obstetrics

of 23.5 Montevideo units after each of two 40 mg. injections. In this case, the drop in over-all uterine activity was due to lower intensity contractions with accompanying slight increases in both frequency and tone. In 13 cases administration of the stated drug resulted in increased intensity; in 12 cases the intensity decreased. The average rise in intensity was 7.7 mm. Hg and the average drop was 3.6 mm. Hg. In 20 cases there was an increase in fre-

DILATATION 6 cm I

UTERINE

ACTIVITY

INTENSITY

TONE

(MONTEVIDEO

UNITS)

(mm/t-lg)

FREQUENCY

137.40 27.20

(CONTRACTIONS/IO

MINUTES)

(mm/Hg)

5.040 II.20

DILATATION 6 cm

UTERINE

ACTIVITY

INTENSITY

B

FREQUENCY TONE

Fig. 2. A, Control period, tine, 45 mg. intravenously, to 3 minutes.

(MONTEVIDEO

UNITS)

(mm/Hq) (CONTRACTIONS/IO

835

143.68 32.20

MINUTES

(mm/Hg) before injection of pentazocine. B, Period showing obvious effect on restkssness

4.745 1363 after injection and contractions

of pentazowithin 2

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July 15, 1967 Am. J. Ohst. & Gynrc.

Filler

quency after the administration of pentazotine and in 5 there was a decrease in frequency. The average rise was 1.2 contractions per 10 minute period. The average drop was 0.42 per 10 minute period. After administration of pentazocine there was an increase in tone in 17 cases and a decrease in only 8. The average increase was 3.9 mm. Hg and the average decrease was 1.5 mm. Hg (Figs. 1 through 3). Effect of meperidine on contractility. In

the 12 cases in spontaneous labor, meperidinc was administered during periods of obvious discomfort and anxiety. All patients rxhihitcd a good analgesic response and an iucrease in uterine activity regardless of the point in labor at which the drug was administered. The changes were slight when uterine activity was o\rer 200 Montevideo units at the time of administration. The over-all increase in uterine activity averagrd 74.09 Montevideo units.

DILATATION 4cm

FREQUENCY (CONTRACTIONS/ IO MINUTW

FREQUENCY

Fig. tine,

3. A, Control period, 45 mg. intravenously,

5 minutes.

(CONTRACTI~NS/~~

before injection of pentazocine. showing obvious effect on

MINUTES)

B, Period

after

injection

of pentazo-

restlessness and contractions

within

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96 6

Analgesia

FREQUENCY

ACTIVITY

hlONTEVIDE0

(CONTRACTIONS

UNITS)

/ IO MINUTES)

A DILATATION 6cm

B

UTERINE ACTIVITY

FREQUENCY

(MONTEVIDEO

(CONTRACTIONS/IO

UNITS)

MINUTES)

Fig. 4. A, Control period, before injection of meperidine. B, Period after injection of meperidine, 100 mg. intramuscularly, showing; obvious effect on restlessness and contractions within

24 minutes.

837

Uterine activity at the time of administration varied from 115 Montevideo units to 223 Montevideo units, and cervical dilatation was greater than 7 cm. in all cases. In addition, the vertex was well engaged and the membranes ruptured in all cases. The average increase in uterine activity was 22.96 Montevideo units and in intensity 15 mm. Hg. In 4 of the 8 cases there was a decrease in frequency, averaging 0.92 con-

The intensity increased an average of 9.2 mm. Hg. The frequency increased an average of 1.4 contractions per 10 minute period. The tone increased an average of 3.5 mm. Hg (Figs. 4 through 7). Effect of saddle block on contractility. In 8 cases in which saddle blocks were administered, all exhibited some increase in uterine activity.

UTERINE

in obstetrics

838

Filler, Hall, and Filler

traction per 10 minute period. In the other 4 cases there was an increase in frequenq averaging 0.83 contraction per IO rriinutts period. The uterine tone increased in only 1 case and then only 1.5 mm. of H,q. In the other 7 cases, the tone dropped an average of 2.7 mm. Hg. Contractions appeared uniformly smoother and more regular with an absence of voluntary Inovements (Fig. 8).

Effect of caudal block on contractility. 111 6 cases of caudal block administration, 1- (‘shihited a d(vcase in ilterine acti\,ity. ‘I‘\\Y, showed no apparent change in Ilterinv ac.ti\ it!?. .Onc cast which exhibited a drop of ?A Monte\4deo units was receivin!: stimulation with Syntocinon at the tirtlc of calida block. In this cast the drop in acti\.ity was tl~lc> to

DILATATION

?cm

TIME

O-30

025

0:40

oh5

I

UTERINE

ACTIVITY

INTENSITY

TONE

TIME

UNITS)

114.97

(mm/fig)

FREQUENCY

A

(MONTEVIDEO

20 66

(CONTRACTIONS/IO

6.032

MINUTES)

850

(mm/Hg.)

0:50

or55

UTERINE

ACTIVITY

I.05

too

(MONTEVIDEO

UNITS)

INTENSITY(mm/Hg) FREQUENCY

B

TONE

Fig. 5. A, Control period. dine, 100 mg. intramuscularly,

I? minutes.

264.12 45.98

(CONTRACTIONS/IO

MINUTES)

(mm/Hg) before

1:10

injection of mepefidine. B, Period showing obvious effect on restlessness

5905 8.50 after injection of meperiand contractions within

Analgesia

in obstetrics

839

Fig. 6. A. Spontaneous labor. Control period before injection of meperidine. B, Period after injection of meperidine showing obvious effect on restlessness and contractions within 20 minutes.

Uterine

TIME

Activity (Montevideo

1100

1:05

Uterine

Activity

Units)

1:15

1:10

(Montevideo

1:20

I:25

Units)

[WERIDINE

IOOmg144.~

Uterine Activity (Montevideo Units)

A i Tone (mm/Hg) DllqTnTlON

Fig. 7. A, Spontaneous early labor. Control period before injection of meperidine. B, Slight improvement of contractions after effect of meperidine injection even in early stage of labor.

3cm

BLOOD PRESSURE “x0

Uterine Activity (Montevideo Units)

I3

7 102.92

46.72 2.2 6.1

840

Filler,

Hall,

and

July 15, 1967 :\m. J. Obst. & Gynec.

Filler

‘--

TIME

0115

0:iO

Uterine

Activity

‘Intensity A

(Montevideo

0:25 Units)

115.20

(mm/Hg)

Frequency Tone

0:20

3Q40

(Contractions/

IO minutes)

(mm/l-Q)

4.12 13.00

BLOOD PRESSURE "8hO

9

TIME 0:30

0:35

OKI

PATIENT ASLEEPiLEVELTO T.9

Uterine

Activity

(Montevideo

or45

OKJ

055

BLOODPRESSURE"v 60

Units)

Fig. 8. A, Effect of saddle block on uterine contractility and fetal heart patient restlessness. Deep type I dips present. B, Period of administration up. C, Contractions more regular with increased over-all activity, type

rate. Control with patient I dips much

period, sitting smaller.

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Number

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Analgesia in obstetrics

1XYLOCAINE t5omgcAmALl I IJO o? 60 q 60 ‘E

‘2 0

TIME

I:25

1:30

135

1:40

1:45

133

155 AFTER

BEFORE

Uterine Activity (Montevideo

Fig. 9. The activity after

effect of caudal the block.

block

on

uterine

Units)

contractions

showing

a dxrease

in

uterine

[MEPERIDINE 100mq 14. BLCKIJ PRESSURE ‘x0 PATIENT RESTLESS 1DILATATION 3cm 100 m 80
40 20 0

TIME

1:45

130

1:55

Uterine Activity (Montevideo

A

2:oo

2:05

2:io

Units)

[

SLEEP

TIME -2:i5

230

2:i5

2:io

Uterine Activity (Montevideo Units) Intensity (mm/t-&) Frequency (Contractions/ IO minutes) B

[

Tone (mm/l-@)

2:&l

113.29 21.8 5.620 I4

Fig. 10. A, Oxytocin induction of labor. Control period before injection Period after injection of meperidine, 100 mg. intramuscularly, showing restlessness within 30 minutes and no appreciable effect on contractions.

of meperidine. obvious effect

B, on

84

842

Filler,

Hail,

and

Filler

a decrease in intensity of 14 mm. Hg, despite a slight increase in frequency of 0.2 contraction per 10 minute period (Fig. 9). In the other 3 cases the drop in uterine activity avera
given. Significant type I dips” were SWIM in all cases before the saddle blocks were gi\x.n. The membranes were ruptured and the LY~I‘tcx well engaged in each case. After the> saddle block had taken elfcbct there \\.as :I significant decrease in the amplitude of the type I dips (Fig. 8’). In none of the casc~ were type II dips” present, so nothirlg GUI be said about the effect of saddle blocI\ on this more dangerous type of fetal heart ~xtr: response to uterine contractions. Effect of meperidine on stimulated or induced labor. In 7 cases in which meperidine was ,clven during oxytocin indrlctiorl (31‘ stimulation, the uterine acti\ilv was o\.el 200 Montevideo units at the tirlle of adtnin-

1MEPERIDINE IDDmgI.M.1

60 I” 2 40 E 20 TIME

1:40

I :i5

I:;0

Uterine Activity (Montevideo Units) Intensity (mm/l-Q) Frequency (Contractions/ IO minutes) Tone (mm/Hg)

A

263.36 55 5.029 3.7 -1

PATlEFTSLEEPING 80 \

I”

60

E E

40

“TIME

2:io

2:i5

Uterine Activity (Montevideo

Fig.

11. A, Stimulated labor. Control period, of meperidine showing no essential restlessness within 30 minutes.

injection

before change

2:30

Units)

injection of meperidine. in contractility despite

B, Period after obvious effect on

Analgesia

istration. In 1 case it was 112.8 Montevideo units. Four cases showed a minimal decrease in uterine activity, and 4 a miniInal increase. These changes were all less than 20 Montevideo units. Similarly, there was no significant change in intensity, frequency, or tone. This was despite an ob\iously excellent analgesic effect (Fig. 10). In the 1 case in which the uterine activity was 1 12.8 Montevideo units, a oxytocin induction was in progress. The patient was in rarly labor with the cervix 2 cm. dilated. The meperidine was administered and afterward, despite a good sedative effect? uterine activity was only 113.29 Montevideo units. It must be said that this patient did not appear to be distressed or anxious before the administration of the analgesia. This then is illustrative of what seemed apparent to us throughout the study; that is, that analyesia acts by relieving pain and anxiety and not by a direct effect on uterine muscle.” If the method of analgesia used blocks sympathetic or epinephrine release in any way, it will have the effect of increasing uterine contractility. However, if contractility is already optimum, little or no change in contractility will result even if the analqesia or sedative effect is good. Decrease in activity seems to result when sympathetic tone is increased or parasympathetic influence decreased to create a sympathetic dominance. In 5 patients meperidine was administered after sparteine sulfate stimulation. There were no significant changes in contractility. Uterine activity changed less than 10 Montevideo units in each case. Activity had htscn grrater than 200 Montevideo units in all cases at the time of administration (Fig. I I ). Comment

Our. evidence shows that administration of analgesic drugs to patients in spontaneous labor enhances uterine contractility if they have the desired effect of alleviating pain and anxiety in the patient (Table I). This is true in any stage of labor if the uterine contractions are less than optimum. l’aken

in obstetrics

843

Table I. General effect of methods of analgesia on uterine contractility and suggested mode of action*

Pentazocine Meperidine Saddle block Caudal block Paracervical block Hypnosis Psychological support

i F

J

‘+-+

together with the fact that these drugs appear to have no efftct on optimum contractility whether spontaneous or produced by oxytocic drugs, the mechanism of action seems to be the abolition of an inhibiting force rather than an inherent oxytocic action of their own.” Morphine might be an exception here. 7, lo Caudal block depresses uterine contractility a:, shown here and elsewhere.‘6v l7 Paracerviczl block also seems to inhibit uterine contractility.“s It has been suggested that the inhibition of uterine contractility by caudal and paracervical blocks is due to an interfere:lce with the reflex of Ferguson.‘, lo However, the fact that saddle block or even high spinal anesthesia’? does not depress4 but enhances uterine contractions would speak against this mode of action. It is more probable that caudal and paracervical blocks act by suppressing tht parasympathetic nervous system and allowing sympathetic dom nance of the uterus. Indeed, Hellman16 kas shown numerous cases of transient fetz.1 bradycardia following paracervical block. This may be due to local vasospasm with decreased uterine and placental blood flow. ‘l’his would account for the fetal bradycardia and the depression of the uterine contractions. It may also br ducx to reducing parasympathetic innervation Inorc than it reduces sympathetic innervation, since predominantly sympathetic fibers pass through thr infundibulopelvic ligamerits. This premise ‘s supported by some

844

Filler,

Hall,

and

Filler Am.

excellent work on the autonomic nervous system and its innervation of the uterus done by Shabanah, Toth, and Maughan.“’ It also fits in with the known fact that adrenaline inhibits uterine contractility.‘~ ‘L 2::. 27. 3n. .?,i,39 Pain creates anxiety and stress with the concomitant release of adrenaline.‘“, 30 The alleviation of pain reduces this factor and therefore allows endogenous oxytocin to work unopposed by excesses of epinephrine. There is more evidence to document this point of view. An article on psychological inhibition of labor by Newton, Foshee, and Newton,‘” is a case in point. Hypnosis has been shown to shorten the duration of labor.“, ‘I. ” Many articles on “natural childbirth” methods emphasize the short, easy labor of these patients.“? Unfortunately, because of the very nature of this last method, a controlled study of uterine contractility recording cannot be domne. However, Reynolds”3 has some interesting tracings on improvement of labor in a tense nervous patient after she had been reassured by her obstetrician. Paravertebral or sympathetic block has been shown by Reich?8, 29 to relieve pain and shorten the first stage of labor. Hunter’O has recordings which document increased contractility after paravertebral block. Tetanic contractions or hypercontractility may be produced by oxytocic agents, and usually not by analgesia. As mentioned before, analgesia will exert an effect only when contractility is less than optimum. It is important to bear this in mind when studying the effect of a drug on uterine contractility, since an induced or stimulated labor may well mask the effect of the drug being studied. Our recordings of fetal heart rate have shown that changes have occurred only in those cases in which saddle blocks were given. This change was a decrease in the amplitude of type I dips after the saddle block had taken effect. Since all the saddle blocks were administered to patients with ruptured membranes and the head well engaged in the pelvis, and since the mcchanism of the production of these dips is re-

July 15. l’)bi J. Obat. g: (;~IICL.

lated to pressure on the fetal skull,” the ITlaxation of the perineum proditced here would account for this chan,ge. It must be borne in mind that the respiratory depr,essant effect of analgesic drugs cannot be accurately assessed before birth. It is probablr that a normal fetus with respiratory depression present at birth if properly resuscitated will be unharmed. However. it is apparent that a fetus in distress or in borderline conditions may not be able to overcome the additional strain of drug-induced neonatal respiratory depression. It must be mentioned that if the technique of analgesia causes maternal hypotension and decreased uterine blood flow, both depression of uterine contractility and fetal distress may be produced.“. I13 w None of our patients exhibited hypotension during the study. Conclusion

Uterine contractility at term seems to be regulated by oxytocic agents with sympathetic and parasympathetic influences. Pain is a stimulus which, by producing anxiety in the patient causes increased epinephrine secretion. This, in turn, inhibits uterine contractility. Relief of pain reduces this inhibition and improves contractility. Neural blockade which allows sympathetic dominance will inhibit contractions; whereas sympathetic blockade will improve contractions. Adequate uterine blood flow is essential to maintenance of contractility. Complete neural blockade, as in spinal anesthesia, will allow uninhibited uterine contrartility, provided that profound hypotension dots not result, reducing uterine blood flow. The administration of oxytocics will often override the sympathetic and parasympathetic influences. Therefore. it is hard to evaluate the effect of drugs on labor that is stimulated or induced. Only large doses of drugs that are direct antagonists of oxytocin or directly inhibit the contractility of uterine muscle will have an efIect under these conditions. The commonly used analgesic methods excluding atropine or atropine-like sub-

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98 6

Analgesia

stances, do not change fetal heart rate or the response of fetal heart rate to uterine contractions. The exceptions to this are methods which decrease perineal resistance and therefore the pressure on the fetal head which is almost uniformly present in the later stages of labor. Therefore, it behooves us to bear constantly in mind that the respiratory depressant effect of many agents will not be evident until after birth. Summary

The methods of Alvarez and CaldeyroBarcia for continuous study of intra-amniotic pressures were used to study the effects of analgesic methods on uterine contractions on 64 patients in labor at term. In addition, the continuous recording of fetal heart rate using the electrocardiographic and cardio:achometric methods of Pantle determined the effects of these methods of analgesia on fetal heart rate. Twenty-five patients received pentazocine for analgesia. Twenty-five patients received Meperidine hydrochloride for analgesia. Eight patients received saddle blocks and 6 received caudal blocks. Our results showed that uterine contractility was, in general, enhanced by all of thece methods except caudal block. It was postulated with the supporting evidence

REFERENCES

The assistance of Mrs. Margit Piket and Mrs. Selma Ladenheim in the conduct of this study is gratefully acknowledged.

8. Caldeyro-Barcia,

Alexander, J. A.. and Franklin, R. R.: Obst. & Gvnec. 27: 436. 1966. 2. Al&q H., and’ Caldeyro-Barcia, R.: Surg., Gynec. & Obst. 91: 1, 1950. 3. Bieniarz, J., Fernandez-Sepulveda, R., and Caldeyro-Barcia, R.: .4~. J. OBST. & GYNEC. 1965.

9. 10. Il. 12.

Brady, J., James, L. S., and Baker, M. A.: AM. J. OBST. & GYNEC. 86: 785, 1963. 5. Buena-Montano, M.: AM. J. OBST. & GYNEC.

4.

94:

6.

1062,

845

from many other sources that enhancement of uterine contractions results from a decrease in the anxietv caused by pain. This is due to a decrease in epinephrine production. It was further suggested that methods which inhibit the sympathetic influence on the uterus enhance uterine contractility. Conversely, methods which increase sympathetic dominance on the uterus depress uterine contractility. The methods of analgesia studied did not affect the fetal heart rate, except for saddle blocks. In the saddle block cases a decrease in the amplitude of type I dips was observed. It is suggested that since newborn respiratory depression attributable to many analgesic drugs cannot be evaluated in the fetus, these must be lrsed with extreme caution. The use of oxytocic agents may override the sympathetic and parasympathetic influences on the uterus. Therefore, the evaluation of the influence of any drugs on uterine contractility may be inaccurate in induced or stimulated labor.

1.

92: 821,

in obstetrics

1966.

Caldeyro-Barcia,

13. 14.

R.,

Mend&-Bauer,

C.,

Poseiro, J. J., Escarcena, B. S., Pose, S. V., Bieniarz, J., Arnt, I., Gulin, L., and Althabe, 0.: Control of Human Fetal Heart Rate During Labor, in Donald E. Cassels, editor: The Heart and Circulation in the Newborn Infant, 1965. 7. Caldeyro-Barcia, R., Alvarez, H., and Poseiro, fg5Js1: Arch. Int. Pharmacodyn. 101: 171,

15. 16.

17.

18.

R , and Poseiro, J. J.: Clin. Obst. & Gynec. 3: 386, 1960. Davidson, J. A.: Brit. M. J. 2: 951, 1962. DeBodo, R. C.: j. Pharmacol. & Exper. Therap. 82: 74, 1944. Ebner, H., Barcohana, J., and Bartoshuk, A. K.: AM. J. OBST. Sr GYNEC. 80: 569, 1960.

Ferguson, J. K. W.: Surg., Gynec. & Obst. 73: 359, 1941. Filler, W. W., Jr., and Filler, N.: Obst. Sr Gynec. 28: 224, 1966. Friedman, E. A.: Bull. Sloan Hosp. Women 1: 42, 1955. Garcia, C. R., and Garcia, E. S.: AM. J. OBST. & GYNEC. 69: 812, 1955. Hellman, L.: Personal communication. Tafeen, C. H., Freedman, H. L., and Harris, H.: AM. J. OBST. & GYNEC. 94: 854, 1966. Hingson, R. A., Gull, W. A., and Benninger, M.: Anesth. & Aralg. 40: 119, 1961. Hon, E. H.: AM. J. OBST. & GINEC. 83: 333, 1962.

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19. 20. 21.

22.

23. 24. 25. 26.

27. 28. 29.

Filler,

Hall,

and

Filler

Hon, E. H.: Clin. Obst. & Gynec. 3: 860. 1960. Hunter. C. A., Jr,: AM. J. OBST. & GVNEC. 85: 681, 1963. James, L. S.: Acidosis of the Newborn and Its Relation to Birth Asphyxia. IX. Congress of Paediatrics, Montreal, Canada, July. 1959. pp. 17-22. James, L. S., Weisbrot, I. M., Prince. C. E., Holaday, D. A., and Apgar, V.: J. Pediat. 52: 379, 1958. Kaiser, I. H., and Harris. J. S.: AM. J. OBST. & GYNEC. 59: 775, 1950. Larks, S. D.: Obst. & Gynec. 22: 427, 1963. Newton, N.. Foshee, D., and Newton, M.: Obst. & Gyncc. 27: 371, 1966. Pantle, J.: Method for Detecting the R Wave of the Foetal Electrocardiogram for the Continuous Control of the Foetal Heart Rate During Labor, Pror. II International Conference Medical Electronics, Paris, London, 1959, Illife and Sons, Ltd., Publishers. Pose, S. V., Cibils, L. A., and Zuspan, F. P.: AM. J. OBST. & GYNEC. 84: 297,-1962. 1: 672. 1953. Reich, A. M.: Obst. & Gvnec. Reich; A. M.: AM. J. O&T. & GYN~. 61: 1263, 1951.

30.

Reynolds, S. R. M.: Physiology of the Uterus, ed. 2. New York, 1949, Paul B. Hoeber. Inc.. p. 223. 31. Reynolds, S.- R. M.: Physiology of the Uterus. cd. 2. New York. 1949. Paul B. Hoeber. Inc.. p. 243. 32. Reynolds, S. R. M.: Physiology of the Uterus. cd. 2, New York. 1949, Paul B. Hoeber, Inc., p. 234. 33. Reynolds, S. R. M.: Physiohjgy of tht, ITterm, rd. 2, New York. 1939. Paul B. Hoeber, Inc., p. 239. 3-1. Rodriquez-Lopez, M., Reynolds, S. R. M.. and Caldeyro-Barcia, R.: Arch. ginrc. Montrvideo 9: 16, 1950. 35. Shabanah, E. H., Toth, A., and Maughan. G. B.: AM. J. OBST. & GYNEC. 89: 841, 1964. 36. Stroup, P. E.: AM. J. OBST. & G~NEC. 84: 595, 1962. 37. Vasicka, .4.. Hutchinson, H. T., Eng, M.. and Allen, C. R.: AM. J. OBST. & GYNEC. 90: 800, 1964. 38. Zourlas, P. A., and Kumar, D.: .4~. J. 0~s~. & GYNEC. 91: 217, 1965. 39. Zuspan, F. P., Cibils, L. A., and Pose, S. V.: AM. J. OBST. & GYNEC. 84: 841, 1962.