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The effect of scopolamine on fetal heart rate baseline variability
The effect of scopolamine on fetal heart rate baseline variability FRANK
H.
BOEHM,
JAMES
H.
GROWDON,
Nashville,
M.D.,
F.A.C.O.G. JR.,
M.D.
Tennessee
The eflect on FHR baseline variability of intravenous scopolamine (0.43 administered alone and in combination with Demerol (SO mg.) and Largon was evaluated. A decrease in baseline variability was found in nine of 19 given scopolamine (0.43 mg.). When scopolamine, Demerol, and Largon simultaneously, a change in baseline variability was observed in nine of i.? No change in variable or early deceleration FHR patterns was observed.
ALONG WITH fetal heart rate (FHR) deceleration patterns, FHR baseline variability has been shown to be another indicator in fetal monitoring. IS8 Baseline variability, however, has been shown to be modified not only by fetai distress but also by other factors such as fetal immaturity and the administration of certain drugs to the mother.6 Vanderbilt University Hospital and Nashville General Hospital fetal intensive-care units currently offer, by means of Xerox 400 Telecopier, a consultation service to several outlying hospitals which have recently acquired fetal monitors.? With the responsibility of interpreting incoming FHR tracings has come the realization that the effect of commonly used drugs on FHR patterns, especially baseline variability, must be clarified in order to prevent a possible misinterpretation of data and mismanagement of patients. One such drug often used by obstetricians requesting consultation is scopolamine. It has From the Department Gynecology, Vanderbilt Hospital and Nashville General Hospital. Received for publication 1973. Revised Accepted
June July
of Obstetrics University Metropolitan December
mg.) (20 mg.) patients were infused patients.
been given in combination with analgesics and antiemetics to produce amnesia in laboring patients. It was our clinical impression that such a combination of drugs diminished the FHR baseline variability. This study was designed to determine the effect on FHR variability of scopolamine, alone and in combination with drugs with which it is commonly used. Methods The patients were admitted to the fetal intensive-care units of Vanderbilt University Hospital or Na.shville General Hospital. Only those patients with uncomplicated antepartum histories were included in the study. FHR monitoring was obtained with Corometric FMS 101~ units. The beat-to-beat FHR was computed with the intervals brtween fetal electrocardiographic peaks (K waves) by a peak detecting digital tachometer gaining input via a spiral fetal scalp electrode. Uterine contractions were determined either by a transcervical intra-amniotic tetrafluorethylene catheter attached to a Statham strain gauge or by an external pressure transducer. The FHR was examined for changes in high-frequency (180 c.p,m.) and low-frequency (3 to 5 c.p.m.) variability as described by Yeh and associate@ (Fig. 1) . Be-
and
7,
24, 1974. 15, 1974.
Reprint requests: Dr. James H. Growdon, Jr., Nashville Metropolitan General Hospital, Nashville, Tennessee 37210.
1099
1100
Boehm
and
December Am. J. Obstet.
Growdon
15, 1974 Gynecol.
Fig. 1. Baseline variability (cycles per minute), A, Loss of high frequency, normal low frequency; B, normal high and low frequency ; C, loss of high and low frequency ; D, normal high frequency, loss of low frequency. (Modified from Yeh et al.: Obstet. Gynecol. 41: 355, 1973, Fig. 2, A-D. )
Fig. 2. Characteristic
example of each classification
fore and after drug infusion, each FHR pattern was classified as showing marked, moderate, minimal, or absent high- and low-frequency variability. Fig. 2 shows characteristic examples of each classification. Changes in acceleration or deceleration patterns and in baseline levels were also evaluated. A baseline FHR pattern was established for a minimum of 10 minutes prior to the intravenous infusion of the medication. Following the infusion, the FHR pattern was evaluated
of baseline variability.
for 60 minutes prior to any subsequent infusion of medication. The drugs studied were scopolamine (0.43 mg.) i Demerol” (50 mg.) , and Largont (20 mg. ) . Scopolamine was given alone to 19 pa.tients (Table I) . In four patients, scopolamine was given 60 minutes after previous ‘Demerol, York, New
Meperidine York.
HCl,
flagon, Propiomazine delphia, Pennsylvania.
HCI,
Breon Wyeth
Laboratories, Laboratories,
New Phila-
Volume Number
120 8
Scopolamine
Fig.
3. Representative
change
in baseline
Largon infusion. Eight patients received scopolamine after previous infusion with Demerol. Largon was given first in 13 patients. Nine patients received Largon 60 minutes after scopolamine. Demerol was given first to nine patients. Demerol, after previous infusion of scopolamine, was given to four patients Demerol, Largon, and scopolamine in combination were given to 12 patients. Results When scopolamine was given alone, 47 per cent of patients showed reduction in baseline variability (Table I). A reduction in baseline variability was noted in 27 per cent of patients receiving scopolamine after Demerol infusion and 25 per cent of patients receiving scopolamine after Largon infusion. Therefore, 42 per cent of the patients given scopolamine (0.43 mg.) , alone or in sequence with the other drugs studied, showed a change in baseline variability (Fig. 3) . Subsequent to scopolamine infusion, 39 per cent of these patients had an elevation of baseline greater than 10 beats per minute.
variability
after
on
scopolamine
FHR
1101
infusion.
Table
I. Change in baseline subsequent to drug infusion
Intravenous
variability
medication
Scopolamine Scopolamine after Demerol Scopolamine after Largon Largon Largon after scopolamine Demerol Demerol after scopolamine Demerol, Largon, and scopolamine
variability
:-,..
~ 19 8 4 13 9 9 4
9 3 1 5 0 2 1
12
9
A decrease in baseline variability was seen in 40 per cent of patients given Largon alone. None of the nine patients receiving Largon after previous infusion of scopolamine revealed change. Therefore, 23 per cent of patients given 20 mg. of Largon, alone or iri sequence after scopolamine, evidenced change in baseline variability (Fig. 4). Decreased
baseline
variability
was
seen
in
1102
December Am. J. Obstet.
Boehm and Growdon
Fig. 4. Representative
change in baseline variability
19 per cent of patients receiving Demerol alone. When Demerol infusion followed scopolamine infusion by 60 minutes, 25 per cent of patients showed decreased baseline variability. Therefore 23 per cent of patients given Demerol, alone or in sequence after scopolamine, showed decreased baseline variability (Fig. 5). When the combination of Demerol, Largon, and scopolamine was given simultaneously, 75 per cent of patients showed decreased baseline variability (Fig. 6) . Early and variable deceleration patterns noted incidentally during the study periods did not seem to be modified by the drug infusion. Comment Loss of baseline variability has been noted to be an early indication of fetal distress. In association with late ’ deceleration or severe variable deceleration patterns, especially in the presence of tachycardia, the loss of baseline variability has been shown to be ominous.ls 8-14 Atropine has been shown many times to
15, 1974 Cynecol.
after Largon infusion.
cause a decrease in baseline variability, as well as to cause an increase in the baseline FHR and modification of deceleration patterns.l”-I” Scopolamine is closely related to atropine, the former being a levorotatory form of the parent compound, hyoscine, whereas atropine is a racemic mixture. It is not surprising, therefore, that scopolamine might produce some of these same changes in the FHR tracing. The use of scopolamine during labor to produce amnesia is a time-honored technique. Several investigators have used scopolamine during FHR monitoring.l’x 18, “O, “I However, only ShenkeP noted that the beat-to-beat variability had to be interpreted cautiously when scopolamine was employed. He stated that “diminution in beat-to-beat variation, that is minimal variation of FHR, occurred so often when scopolamine was used during labor, that only absence of fluctuation of rate was a valid prognostic sign.” This study shows that when scopolamine (0.43 mg.) is given, even without the addition of commonly used analgesics and antiemetics, a decrease in baseline variability
Scopolamine
Fig.
5. Representative
Fig. 6. Representative infusion.
change
change
in
baseline
in baseline
variability
variability
after
after
Demerol
scopolamine,
on
FHR
variability
infusion.
Demerol,
and
Largon
1103
1104
Boehm and Growdon
occurs in 42 per cent of patients. Occasionally, it is also associatedwith complete lossof beat-to-beat change as well as with elevation of the baseline. In combination with commonly used analgesicsand antiemetics, which themselves do produce changes in baseline variability in 25 per cent of cases,scopolamine is associatedwith a diminution or loss of variability in 75 per cent of subjects. In practice, although most commonly administered by routes other than intravenous, larger doses of scopolamine in combination with greater amounts of total analgesicsand antiemetics than used in this study are usually employed. Studies of these drugs at these
REFERENCES Davidsen, P. C. B.: Acta Obstet. Gynecol. Stand. 50: 51, 1971. 2. Schifrin, B. S.: J. A. M. A. 222: 196, 1972. 3. Gabert, H. A., and Stenchever, M. A.: AEX. J. OBSTET. GYNECOL. 115: 919, 1973. 4. Perinatal Medicine, New York, 1969, Academic Press, Inc., pp. 80-93. 5. Goodlin, R. C.: Obstet. Gynecol. 40: 265, 1972. 6. Yeh, S., Forsythe, A., and Hon, E. H.: Obstet. Gynecol. 41: 355, 1973. 7. Boehm, F. H., and Goss, D. A.: Obstet. Gynecol. 42: 475, 1973. 8. Schifrin, B. S., and Dame, L.: J. A. M. A. 219: 1322, 1972. 9. Paul, R. H., and Hon, E. H.: Obstet. Gynecol. 31: 779, 1971. 10. Paul, R. H.: Aaa. J. OBSTET. GYNECOL. 113: 573, 1972. 11. Shenker, L.: AM. J. OBSTET. GYNECOL. 115: 1111, 1973. 12. Goodlin, R. C.: AM. J. OBSTET. GYNECOL. 110: 210, 1971. 1.
Am.
December J. Obstet.
15, 1974 Gynecd.
greater concentrations might well show evidence of change in baseline variability in even a larger percentage of patients. Also, since at&pine shows a modification of deceleration patterns, largkr dosesof scopolamine need to be evaluated, since scopolamine (0.43 mg.) had no noticeable effect on early or variable deceleration patterns. When interpreting the significance of FHR baseline variability, a critical review of the patient’s medication is mandatory. When monitoring a “high-risk” labor patient, certainly, the use of medications known to mask changes in the FHR or mimic changes associated with fetal distressshould be avoided.
13. 14. 15. 16. 17. 18. 19.
20.
21.
Hon, E. H., and Yeh, S. : Med. Res. Eng. Oct.-Nov.: 14, 1969. Burnard, E. 0.: Br. Med. J. 13: 1495, 1959. Hon, E. H., Bradfield, A. H., and Hess, 0. W.: AM.J. OBSTET. GYNECOL. 82: 291, 1961. Hon, E. H., and Lee, S. T.: AM. J. OBSTET. GYNECOL. 87: 814, 1963. Hon, E. H.: Obstet. Gynecol. 22: 137, 1963. Renou, P., Newman, W., and Wood, C.: AM. J. OBSTST. GYNECOL. 105: 949, 1969. Caldeyro-Barcia, R., Mendez-Bauer, C., Poseiro, J. J., et al.: In Cassels, D. E., editor: The Heart and Circulation in the Newborn and Infant, New York, 1966, Grune & Stratton, Inc., pp. 7-36. Bieniarz, J., Fernandez-Sepulveda, R., and Caldeyro-Barcia, R.: AM. J. OBSTET. GYNECOL. 92: 832, 1965. Smiler, B. G., Bartholomew, E. G., and Sivak, B. J.: AM. J. OBSTET. GYNECOL. 116: 326, 1973.
H.
BOEHM,
JAMES
H.
GROWDON,
Nashville,
M.D.,
F.A.C.O.G. JR.,
M.D.
Tennessee
The eflect on FHR baseline variability of intravenous scopolamine (0.43 administered alone and in combination with Demerol (SO mg.) and Largon was evaluated. A decrease in baseline variability was found in nine of 19 given scopolamine (0.43 mg.). When scopolamine, Demerol, and Largon simultaneously, a change in baseline variability was observed in nine of i.? No change in variable or early deceleration FHR patterns was observed.
ALONG WITH fetal heart rate (FHR) deceleration patterns, FHR baseline variability has been shown to be another indicator in fetal monitoring. IS8 Baseline variability, however, has been shown to be modified not only by fetai distress but also by other factors such as fetal immaturity and the administration of certain drugs to the mother.6 Vanderbilt University Hospital and Nashville General Hospital fetal intensive-care units currently offer, by means of Xerox 400 Telecopier, a consultation service to several outlying hospitals which have recently acquired fetal monitors.? With the responsibility of interpreting incoming FHR tracings has come the realization that the effect of commonly used drugs on FHR patterns, especially baseline variability, must be clarified in order to prevent a possible misinterpretation of data and mismanagement of patients. One such drug often used by obstetricians requesting consultation is scopolamine. It has From the Department Gynecology, Vanderbilt Hospital and Nashville General Hospital. Received for publication 1973. Revised Accepted
June July
of Obstetrics University Metropolitan December
mg.) (20 mg.) patients were infused patients.
been given in combination with analgesics and antiemetics to produce amnesia in laboring patients. It was our clinical impression that such a combination of drugs diminished the FHR baseline variability. This study was designed to determine the effect on FHR variability of scopolamine, alone and in combination with drugs with which it is commonly used. Methods The patients were admitted to the fetal intensive-care units of Vanderbilt University Hospital or Na.shville General Hospital. Only those patients with uncomplicated antepartum histories were included in the study. FHR monitoring was obtained with Corometric FMS 101~ units. The beat-to-beat FHR was computed with the intervals brtween fetal electrocardiographic peaks (K waves) by a peak detecting digital tachometer gaining input via a spiral fetal scalp electrode. Uterine contractions were determined either by a transcervical intra-amniotic tetrafluorethylene catheter attached to a Statham strain gauge or by an external pressure transducer. The FHR was examined for changes in high-frequency (180 c.p,m.) and low-frequency (3 to 5 c.p.m.) variability as described by Yeh and associate@ (Fig. 1) . Be-
and
7,
24, 1974. 15, 1974.
Reprint requests: Dr. James H. Growdon, Jr., Nashville Metropolitan General Hospital, Nashville, Tennessee 37210.
1099
1100
Boehm
and
December Am. J. Obstet.
Growdon
15, 1974 Gynecol.
Fig. 1. Baseline variability (cycles per minute), A, Loss of high frequency, normal low frequency; B, normal high and low frequency ; C, loss of high and low frequency ; D, normal high frequency, loss of low frequency. (Modified from Yeh et al.: Obstet. Gynecol. 41: 355, 1973, Fig. 2, A-D. )
Fig. 2. Characteristic
example of each classification
fore and after drug infusion, each FHR pattern was classified as showing marked, moderate, minimal, or absent high- and low-frequency variability. Fig. 2 shows characteristic examples of each classification. Changes in acceleration or deceleration patterns and in baseline levels were also evaluated. A baseline FHR pattern was established for a minimum of 10 minutes prior to the intravenous infusion of the medication. Following the infusion, the FHR pattern was evaluated
of baseline variability.
for 60 minutes prior to any subsequent infusion of medication. The drugs studied were scopolamine (0.43 mg.) i Demerol” (50 mg.) , and Largont (20 mg. ) . Scopolamine was given alone to 19 pa.tients (Table I) . In four patients, scopolamine was given 60 minutes after previous ‘Demerol, York, New
Meperidine York.
HCl,
flagon, Propiomazine delphia, Pennsylvania.
HCI,
Breon Wyeth
Laboratories, Laboratories,
New Phila-
Volume Number
120 8
Scopolamine
Fig.
3. Representative
change
in baseline
Largon infusion. Eight patients received scopolamine after previous infusion with Demerol. Largon was given first in 13 patients. Nine patients received Largon 60 minutes after scopolamine. Demerol was given first to nine patients. Demerol, after previous infusion of scopolamine, was given to four patients Demerol, Largon, and scopolamine in combination were given to 12 patients. Results When scopolamine was given alone, 47 per cent of patients showed reduction in baseline variability (Table I). A reduction in baseline variability was noted in 27 per cent of patients receiving scopolamine after Demerol infusion and 25 per cent of patients receiving scopolamine after Largon infusion. Therefore, 42 per cent of the patients given scopolamine (0.43 mg.) , alone or in sequence with the other drugs studied, showed a change in baseline variability (Fig. 3) . Subsequent to scopolamine infusion, 39 per cent of these patients had an elevation of baseline greater than 10 beats per minute.
variability
after
on
scopolamine
FHR
1101
infusion.
Table
I. Change in baseline subsequent to drug infusion
Intravenous
variability
medication
Scopolamine Scopolamine after Demerol Scopolamine after Largon Largon Largon after scopolamine Demerol Demerol after scopolamine Demerol, Largon, and scopolamine
variability
:-,..
~ 19 8 4 13 9 9 4
9 3 1 5 0 2 1
12
9
A decrease in baseline variability was seen in 40 per cent of patients given Largon alone. None of the nine patients receiving Largon after previous infusion of scopolamine revealed change. Therefore, 23 per cent of patients given 20 mg. of Largon, alone or iri sequence after scopolamine, evidenced change in baseline variability (Fig. 4). Decreased
baseline
variability
was
seen
in
1102
December Am. J. Obstet.
Boehm and Growdon
Fig. 4. Representative
change in baseline variability
19 per cent of patients receiving Demerol alone. When Demerol infusion followed scopolamine infusion by 60 minutes, 25 per cent of patients showed decreased baseline variability. Therefore 23 per cent of patients given Demerol, alone or in sequence after scopolamine, showed decreased baseline variability (Fig. 5). When the combination of Demerol, Largon, and scopolamine was given simultaneously, 75 per cent of patients showed decreased baseline variability (Fig. 6) . Early and variable deceleration patterns noted incidentally during the study periods did not seem to be modified by the drug infusion. Comment Loss of baseline variability has been noted to be an early indication of fetal distress. In association with late ’ deceleration or severe variable deceleration patterns, especially in the presence of tachycardia, the loss of baseline variability has been shown to be ominous.ls 8-14 Atropine has been shown many times to
15, 1974 Cynecol.
after Largon infusion.
cause a decrease in baseline variability, as well as to cause an increase in the baseline FHR and modification of deceleration patterns.l”-I” Scopolamine is closely related to atropine, the former being a levorotatory form of the parent compound, hyoscine, whereas atropine is a racemic mixture. It is not surprising, therefore, that scopolamine might produce some of these same changes in the FHR tracing. The use of scopolamine during labor to produce amnesia is a time-honored technique. Several investigators have used scopolamine during FHR monitoring.l’x 18, “O, “I However, only ShenkeP noted that the beat-to-beat variability had to be interpreted cautiously when scopolamine was employed. He stated that “diminution in beat-to-beat variation, that is minimal variation of FHR, occurred so often when scopolamine was used during labor, that only absence of fluctuation of rate was a valid prognostic sign.” This study shows that when scopolamine (0.43 mg.) is given, even without the addition of commonly used analgesics and antiemetics, a decrease in baseline variability
Scopolamine
Fig.
5. Representative
Fig. 6. Representative infusion.
change
change
in
baseline
in baseline
variability
variability
after
after
Demerol
scopolamine,
on
FHR
variability
infusion.
Demerol,
and
Largon
1103
1104
Boehm and Growdon
occurs in 42 per cent of patients. Occasionally, it is also associatedwith complete lossof beat-to-beat change as well as with elevation of the baseline. In combination with commonly used analgesicsand antiemetics, which themselves do produce changes in baseline variability in 25 per cent of cases,scopolamine is associatedwith a diminution or loss of variability in 75 per cent of subjects. In practice, although most commonly administered by routes other than intravenous, larger doses of scopolamine in combination with greater amounts of total analgesicsand antiemetics than used in this study are usually employed. Studies of these drugs at these
REFERENCES Davidsen, P. C. B.: Acta Obstet. Gynecol. Stand. 50: 51, 1971. 2. Schifrin, B. S.: J. A. M. A. 222: 196, 1972. 3. Gabert, H. A., and Stenchever, M. A.: AEX. J. OBSTET. GYNECOL. 115: 919, 1973. 4. Perinatal Medicine, New York, 1969, Academic Press, Inc., pp. 80-93. 5. Goodlin, R. C.: Obstet. Gynecol. 40: 265, 1972. 6. Yeh, S., Forsythe, A., and Hon, E. H.: Obstet. Gynecol. 41: 355, 1973. 7. Boehm, F. H., and Goss, D. A.: Obstet. Gynecol. 42: 475, 1973. 8. Schifrin, B. S., and Dame, L.: J. A. M. A. 219: 1322, 1972. 9. Paul, R. H., and Hon, E. H.: Obstet. Gynecol. 31: 779, 1971. 10. Paul, R. H.: Aaa. J. OBSTET. GYNECOL. 113: 573, 1972. 11. Shenker, L.: AM. J. OBSTET. GYNECOL. 115: 1111, 1973. 12. Goodlin, R. C.: AM. J. OBSTET. GYNECOL. 110: 210, 1971. 1.
Am.
December J. Obstet.
15, 1974 Gynecd.
greater concentrations might well show evidence of change in baseline variability in even a larger percentage of patients. Also, since at&pine shows a modification of deceleration patterns, largkr dosesof scopolamine need to be evaluated, since scopolamine (0.43 mg.) had no noticeable effect on early or variable deceleration patterns. When interpreting the significance of FHR baseline variability, a critical review of the patient’s medication is mandatory. When monitoring a “high-risk” labor patient, certainly, the use of medications known to mask changes in the FHR or mimic changes associated with fetal distressshould be avoided.
13. 14. 15. 16. 17. 18. 19.
20.
21.
Hon, E. H., and Yeh, S. : Med. Res. Eng. Oct.-Nov.: 14, 1969. Burnard, E. 0.: Br. Med. J. 13: 1495, 1959. Hon, E. H., Bradfield, A. H., and Hess, 0. W.: AM.J. OBSTET. GYNECOL. 82: 291, 1961. Hon, E. H., and Lee, S. T.: AM. J. OBSTET. GYNECOL. 87: 814, 1963. Hon, E. H.: Obstet. Gynecol. 22: 137, 1963. Renou, P., Newman, W., and Wood, C.: AM. J. OBSTST. GYNECOL. 105: 949, 1969. Caldeyro-Barcia, R., Mendez-Bauer, C., Poseiro, J. J., et al.: In Cassels, D. E., editor: The Heart and Circulation in the Newborn and Infant, New York, 1966, Grune & Stratton, Inc., pp. 7-36. Bieniarz, J., Fernandez-Sepulveda, R., and Caldeyro-Barcia, R.: AM. J. OBSTET. GYNECOL. 92: 832, 1965. Smiler, B. G., Bartholomew, E. G., and Sivak, B. J.: AM. J. OBSTET. GYNECOL. 116: 326, 1973.