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ORIGINAL RESEARCH |
From the Departments of Gynecology and Obstetrics and Anesthesia, Sheba Medical Center, Tel-Hashomer; and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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ABSTRACT |
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METHODS: We prospectively studied 145 term singleton deliveries where epidural analgesia was administered. The patients were randomly allocated before the administration of epidural analgesia to receive an intravenous infusion of 10 mg ephedrine, after epidural induction, followed by a continuous infusion for 60 minutes of 20 mg ephedrine (study group) or to receive no ephedrine (control group). The FHR tracing was evaluated for 20 minutes before and 40 minutes after initiating epidural analgesia. Demographic data and clinical and delivery outcome were assessed and compared between the 2 groups.
RESULTS: Injection of ephedrine significantly reduced the rate of major FHR changes appearing 15–25 minutes after induction of epidural analgesia in the study group compared with the control group (2/72 compared with 11/73, respectively; P = .009). To avoid 1 case of adverse FHR changes, 6.8 women should be treated with ephedrine.
Maternal and fetal characteristics and outcome and mode of delivery were similar in the 2 groups. Mean arterial pressure was significantly higher in the study group from the time of analgesia induction and during the subsequent 25 minutes. Maternal heart rate was transiently reduced in the study group only.
CONCLUSION: Ephedrine administration during the time of epidural analgesia initiation can reduce the frequency of adverse FHR changes commonly observed immediately afterward.
LEVEL OF EVIDENCE: I
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PATIENTS AND METHODS |
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Consenting eligible patients were randomly allocated to the study and control groups using computer-generated random codes sealed in opaque envelopes. The institution's Review Board approved the study protocol, and all participants gave their written informed consent.
The epidural analgesia protocol for both groups included infusion of 3 mL of 2% lidocaine (Abbot Laboratories, Abbot Park, IL), as a test dose, followed by injection of 8 mL of 0.25% bupivacaine (Marcaine, Kamada, Rehovot, Israel) for analgesia induction and a continuous infusion consisting of 0.125% bupivacaine with 4 µg/mL of fentanyl (Tenly, Taro Pharmaceutical, Yakum, Israel) by a patient-controlled anesthesia pump at a rate of 6 mL/h. A 6 mL booster dose was allowed every 20 minutes.
Five minutes after the injection of the test dose, women in the study group received an intravenous injection of 10 mg of ephedrine (Abbot Laboratories, Abbot Park, IL) followed by a continuous drip of 20 mg ephedrine in 1 L of Ringer lactate over 60 minutes.
The FHR tracing was interpreted by 2 experienced obstetricians blinded to ephedrine use. An adverse FHR was defined as severe variable deceleration, prolonged deceleration, or a baseline change (bradycardia). A severe variable deceleration was defined as a decrease from the baseline for more than 60 beats per minute (bpm) that lasts more than 60 seconds. The decrease from the baseline of 15 bpm or greater, lasting more than 2 minutes, but less than 10 minutes from onset to return to baseline. A prolonged deceleration was defined as of 10 minutes or more is a baseline change, as defined by the National Institute of Child Health and Human development research planning workshop.10 Other FHR variables that were examined included baseline FHR, accelerations, and number of uterine contractions in 10 minutes in 3 time windows after ephedrine injection (0–10, 15–25, and 35–45 minutes).
Demographic characteristics obtained included maternal age, height and weight (for calculation of body mass index), gravidity, parity, gestational age, neonatal birth weight, and neonatal Apgar score less than 7 at 5 minutes of life. Physical variables included systolic and diastolic blood pressure and maternal heart rate measured by an automatic blood pressure monitor 5 minutes before and every 5 minutes until 30 minutes after analgesia induction. Hypotension was defined as a maternal systolic blood pressure below 80% of baseline recordings or an absolute value of less than 90 mmHg.
Clinical variables included cervical dilatation and fetal head station at the time of analgesia induction, oxytocin use before epidural analgesia, and whether it was stopped. In addition, presence of meconium in the amniotic fluid and mode of delivery were evaluated.
Assuming that adverse FHR changes as a result of epidural analgesia occur in 20% of the women, we calculated that 65 women would be required in each group to detect an 85% reduction in the frequency of adverse intrapartum FHR changes as a result of our intervention, ie, using ephedrine during induction of epidural analgesia, with an 
= 0.05 and a power = 0.8 (1-ß).
Statistical analysis was performed applying single-factor analysis of variance for continuous variables, using Fisher exact tests for dichotomous data or t tests for multiple groups or unpaired t tests for 2 groups (Statview 5.0, Abacus Concepts, Inc.; Berkeley, CA). Statistical significance was assumed at P < .05.
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RESULTS |
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Fetal baseline heart rate was significantly elevated in the study group at both 15–25 minutes and 35–45 minutes after injection of ephedrine (Table 3). The number of accelerations during the 15 to 25–minute window after injection of ephedrine was higher in the study group (70/72 compared with 62/73, respectively; P = .009), but was not different in the first 10 minutes or in the following 35–45–minute window.
Using systolic and diastolic blood pressure measurements, mean arterial pressure (MAP) was calculated. Mean arterial pressure was not statistically different before injection of the epidural test dose, but was significantly higher in the study group, due to a reduction in MAP in the control group, from the time of induction of analgesia and 25 minutes subsequently, becoming comparable 30 minutes after analgesia induction (Fig. 1A). Ten mothers in the control group (13.8%) had a systolic blood pressure drop below 80% of baseline recordings or an absolute value of less than 90 mmHg, whereas none of the mothers in the study group had such blood pressure drop (P = .001). Maternal heart rate in the 2 groups was not statistically different before the injection of the epidural test dose, but was transiently reduced in the study group compared with the control group, after intravenous injection of ephedrine (81.7 ± 13.1 compared with 87.3 ± 15.7 bpm; P = .02). The effect of ephedrine on maternal heart rate waned 5 minutes after injection of the ephedrine and was comparable in the 2 groups (Fig. 1B). There was no significant change due to ephedrine injection in the number of uterine contractions at any time window or between the study and the control groups (Table 3).
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DISCUSSION |
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Ephedrine is widely used for treatment of hypotension during obstetric spinal analgesia,11 yet it is not commonly used to prevent the maternal hemodynamic changes that occur with epidural analgesia during labor. Although our study was designed to assess the influence of ephedrine administration on FHR changes, our results do show that ephedrine also influences maternal hemodynamic characteristics. Unlike previous data by Fong et al,12 who found no benefit in prophylactic administration of ephedrine to reduce the incidence of maternal hypotension after lumbar epidural anesthesia for nonemergency cesarean delivery, we have shown an elevation of the MAP in the study group compared with the control group.
Prophylactic injection of ephedrine was not associated with any maternal or fetal adverse effects. These data are in agreement with previous data by Webb et al13 and by Lee et al,14 who studied the effect of preventive injection of ephedrine before spinal analgesia for cesarean delivery. Although ephedrine can cross the placental barrier, its use during labor is not associated with changes in fetal hemodynamic characteristics, as established using the Doppler technique to measure fetal umbilical and middle cerebral arterial resistance indices.15 Other studies showed no adverse effect on the neonates caused by ephedrine administration.16 However, more studies are needed to exclude the possibility of uncommon adverse consequences of the use of ephedrine.
Adverse changes occurred in 11 of 73 (15%) of control group patients and in only 2 of 72 (5%) of study group patients. However, there was no statistically significant reduction in the study group in the number of cesarean deliveries due to nonreassuring fetal monitoring. In addition, there was no increase in the rate of operative vaginal deliveries in the control group, nor in neonatal outcome. These data are consistent with earlier studies that showed no advantage with regard to reduction in the rate of operative deliveries due to a nonreassuring fetal monitoring.1718 Yet, as in our study, previous studies apparently lacked the statistical power to show the effect of FHR changes on the operative delivery rate. Future multicenter studies may be able to show the effect of preventive ephedrine injection on the rate of operative delivery. Such a study should include approximately 1,000 patients in each study arm.
The mechanism whereby ephedrine works to prevent FHR changes is not clear. Our data show that hemodynamic changes in maternal blood pressure are a possible causal mechanism. Moreover, bolus administration of intravenous ephedrine can increase uterine artery blood flow velocity during uterine contraction. Ephedrine thereby may reverse the decrease in diastolic uteroplacental blood flow velocity and prevent the increase in resistance index during uterine contraction. This suggests that the increase in uterine perfusion pressure during labor could in part restore uterine blood flow to the placenta during uterine contraction.15
In summary, preventive intravenous injection of 10 mg of ephedrine at the time of epidural analgesia induction, followed by a continuous infusion of 20 mg of ephedrine for 60 minutes, can reduce the frequency of nonreassuring FHR traces, which are commonly observed immediately after epidural analgesia. Further studies are needed to determine whether intrapartum ephedrine injection can prevent some of the emergency operative deliveries performed due to nonreassuring changes in FHR.
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Footnotes |
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Received April 3, 2004. Received in revised form July 22, 2004. Accepted July 28, 2004.
doi:10.1097/01.AOG.0000146281.05275.73
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REFERENCES |
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2. Clarke VT, Smiley RM, Finster M. Uterine hyperactivity after intrathecal injection of fentanyl for analgesia during labor: a cause of fetal bradycardia? Anesthesiology 1994;81:1083.[Medline]
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  J. Cleary-Goldman, M. Negron, J. Scott, R. A. Downing, W. Camann, L. Simpson, and P. Flood Prophylactic Ephedrine and Combined Spinal Epidural: Maternal Blood Pressure and Fetal Heart Rate Patterns Obstet. Gynecol., September 1, 2005; 106(3): 466 - 472. [Abstract] [Full Text] [PDF]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
P = .006 compared with placebo.