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OBSTETRIC ANESTHESIA

The Addition of Morphine Prolongs Fentanyl-Bupivacaine Spinal Analgesia for the Relief of Labor Pain

Huei-Ming Yeh, MD^*, Li-Kuei Chen, MD^*, Ming-Kwang Shyu, MD, Chen-Jung Lin, MD^*, Wei-Zen Sun, MD^*, Ming-Jiuh Wang, MD^*, Martin S. Mok, MD, and Shen-Kou Tsai, MD^*

Departments of *Anesthesiology and Gynecology and Obstetrics, National Taiwan University Hospital, Taipei, Taiwan; and Department of Anesthesiology, LAC-USC Medical Center, Los Angeles, California

Address correspondence and reprint requests to Shen-Kou Tsai, MD, Department of Anesthesiology, National Taiwan University Hospital, No 7, Chung-Shan South Rd., Taipei, Taiwan, 100.

	Abstract

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The combination intrathecal fentanyl (25 µg) and bupivacaine (2.5 mg) provides effective labor analgesia for approximately 90 minutes. The purpose of this prospective, randomized, double-blinded investigation was to determine if the addition of morphine (150 µg) to the intrathecal combination of fentanyl (25 µg) and bupivacaine (2.5 mg) would prolong labor analgesia. By using the combined spinal epidural technique, 95 healthy primiparous laboring women in early labor received 2 mL of one of the two intrathecal study solutions, either FB (n = 48): fentanyl (25 µg) and bupivacaine (2.5 mg); or FBM (n = 47): fentanyl (25 µg) and bupivacaine (2.5 mg) plus morphine (150 µg). The mean duration of labor analgesia was significantly longer in the FBM group than in the FB group (252 ± 63 min vs 148 ± 44 min, P < 0.01). There were no significant differences between the two groups regarding the sensory levels, the incidence of nausea, vomiting, pruritus, hypotension, or operative delivery. In conclusion, the addition of 150 µg of morphine to the intrathecal combination of fentanyl plus bupivacaine prolonged the duration of labor analgesia duration without increasing adverse effects.

Implications: The addition of morphine (150 µg) to intrathecal fentanyl (25 µg) and bupivacaine (2.5 mg) prolongs the duration of labor analgesia duration without increasing adverse effects.

	Introduction

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Combined spinal-epidural (CSE) analgesia has gained increasing popularity for providing labor pain relief (1–3). The intrathecal component commonly used in the CSE technique involves the combination of an opioid (fentanyl or sufentanil) plus 2.5 mg of bupivacaine (4). The addition of bupivacaine to the intrathecal opioid provides rapid and profound labor analgesia lasting for two to three hours with minimal maternal or fetal adverse effects (4–9). The use of morphine alone for intrathecal analgesia has a long duration but a slow onset. The addition of morphine to the intrathecal combination of fentanyl and bupivacaine may provide a rapid onset of labor analgesia with a long duration. This prospective, randomized, double-blinded study was designed to determine whether the addition of morphine (150 µg) to the combination of intrathecal fentanyl (25 µg) and bupivacaine (2.5 mg) would prolong labor analgesia.

	Methods

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After IRB approval, 100 primiparous women, ASA physical status I or II, in early labor (cervical dilation 2–5 cm) requesting epidural labor analgesia were enrolled. After informed consent was obtained, women were randomly assigned to receive one of the two intrathecal study solutions, either FB (n = 50): fentanyl (25 µg) and bupivacaine (2.5 mg); or FBM (n = 50): fentanyl (25 µg) and bupivacaine (2.5 mg) plus preservative-free morphine (150 µg). Both study solutions were prepared by a blinded anesthesiologist using 0.9% saline to a total volume of 2 mL.

All women received 1000 mL of IV saline solution before the initiation of labor analgesia. CSE analgesia was performed with the woman in a lateral position at the L2&hyphen;3 or L3&hyphen;4 intervertebral space by using a 16-gauge Tuohy epidural needle. The loss-of-resistance to air technique was used to locate the epidural space. After entering the epidural space, a 27-gauge Whitacre spinal needle was inserted through the epidural needle until the free flow of cerebrospinal fluid was observed. The study solution was then injected, and the spinal needle was removed. Aspiration of cerebrospinal fluid was required before the removal of the spinal needle to confirm the position in the intrathecal space at the end of injection. A 19-gauge epidural catheter was inserted and secured in place. The parturients were informed that they could receive additional analgesia through the epidural catheter on request. The duration of analgesia was defined as the time from injection of the intrathecal study drug until the woman requested additional analgesia via the epidural catheter.

Hypotension was defined as a systolic blood pressure of <90 mm Hg or a 20% reduction from the baseline and was treated with a 250 to 500 mL of IV balanced salt solution administration and 5 to 10 mg of IV ephedrine. Every 5 min for the first 15 min and then every 15 min until additional analgesia was requested, each woman was evaluated by an anesthesiologist blinded to patient group. Blood pressure, heart rate, respiratory rate, and level of consciousness were recorded in every evaluation. The level of consciousness was assessed by using the Glasgow Coma Scale. Pain was assessed by using a 100-mm visual analog scale (VASP) with 0 = no pain, and 100 = worst pain imaginable. Motor blockade was assessed by using the four-point Bromage scale, and the upper level of loss of sensation to pinprick and ice was measured in the midclavicular line 15 min after the injection of study drugs. All women had continuous electronic fetal heart rate monitoring throughout labor and fetal heart rate tracings were evaluated by an obstetrician blinded to the study. Each woman was specifically assessed regarding the occurrence pruritus, nausea, and vomiting during the evaluation. IV administration 10 mg metoclopramide was used to treat nausea and/or vomiting on request and IV 0.15 mg/kg ondansetron was used to treat pruritus on request (10).

Data were expressed as mean ± SD. Student’s t-tests was used for comparison of numeric variables between the two groups while a ² test was used for dichotomous variables. Kaplan-Meier survival analysis was used to compare the cumulative proportion of adequate intrathecal analgesia between the two groups. A P value of <0.05 was considered significant. Group size had been determined by power analysis (ß value 0.9, value 0.05) to detect a 30-min difference in analgesia duration between the groups.

	Results

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The CSE technique was successfully performed in 48 women in the FB group and 47 women in the FBM group. Inability to obtain cerebrospinal fluid occurred in 2 women in the FB group and 3 women in the FBM group, and consequently, the study medications were not administered. These women were excluded from the final data analyses.

There were no statistically significant differences between the two groups regarding demographics, initial cervical dilation, birth weight, and initial VASP scores ( Table 1). All evaluable women reported VASP scores < 10 of 100 within 5 min after the injection of the study solutions. None of the study women delivered before epidural analgesia via the catheter was initiated. Kaplan-Meier analysis showed that the cumulative proportion of adequate analgesia was significantly different between the two groups (Fig. 1) (P < 0.05). The mean duration of labor analgesia was significantly longer in the FBM group (252 ± 63 min) compared with the FB group (148 ± 44 min) (P < 0.01). There was no evidence of lower extremity motor weakness, somnolence, or fetal heart rate abnormalities in any of the women evaluated.

View larger version (15K): [in this window] [in a new window]   Figure 1. Kaplan-Meier analysis of cumulative proportion of adequate intrathecal analgesia. The cumulative proportion of adequate analgesia was significantly different between the two groups (P < 0.05).

	Discussion

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Intrathecal morphine alone (12–13) or in combination with fentanyl or sufentanil (14–15) has been reported. Leighton et al. (14) reported that the intrathecal injection of 250 µg of morphine and 25 µg of fentanyl provided analgesia for labor pain with a rapid onset and an average analgesia duration of 140 to 222 minutes. However, the analgesia duration could not be accurately assessed in that study because more than half of the women delivered within three hours. Grieco et al. (15) reported that adding 250 µg of morphine to intrathecal 10 µg of sufentanil prolonged the duration of labor analgesia but also produced more adverse effects. In our study, we decreased the amount of morphine to 150 µg and found that the incidence of nausea and pruritus was not significantly more frequent than in those women not receiving intrathecal morphine. However, it is possible that this study was not large enough to detect such a difference. The use of a small dose of morphine for women undergoing cesarean delivery has also been reported in several recent studies. Yang et al. (16) reported that 100 µg of intrathecal morphine had fewer adverse effects when compared with 250 µg of intrathecal morphine. In a dose-ranging study reported by Palmer et al.(17), intrathecal morphine in a dose of 75 µg had a similar analgesic effect to that of a dose in 500 µg. We do not know if the dose of morphine used in the present study was optimal because other doses were not tested. Further dose-ranging study is needed to answer this question.

Motor block is undesirable as it may interfere with pushing in the delivery process and thus result in prolonged duration of labor and necessitate instrumental delivery. It is a limitation of this study that the patients were not asked to ambulate and that we used the 4-point scale instead of the modified Bromage scale, which might have provided more detailed information about motor block and the ability to ambulate. We do not know if the parturients in this study could ambulate or not. However, the labor duration and forceps used were not significantly different between the two groups.

The use of drugs other than morphine to prolong the duration of spinal analgesia for labor has been reported. Campbell et al. (18) reported that adding 200 µg of epinephrine to 2.5 mg of bupivacaine and 10 µg of sufentanil resulted in labor analgesia with a duration of 188 minutes. However, excessive motor block was observed. D’angelo et al. (8) reported a duration of labor analgesia of 197 minutes when 50 mg of clonidine was added to 2.5 mg of bupivacaine and 7.5 µg of sufentanil, which however, also nearly doubled the incidence of hypotension. We found an average analgesia duration of 254 min when 150 µg of morphine was added to bupivacaine-fentanyl without increased motor block or hypotension. All the women in our study were primiparous and had long enough labors to allow us the opportunity to evaluate the duration of analgesia. It is conceivable that for multiparous parturients, this regimen would provide analgesia of sufficient duration to make the "one shot" spinal injection for the entire labor course feasible; however, this requires further investigation.

This is the first study to demonstrate a mean duration of spinal labor analgesia more than four hours by using the CSE technique. However, the duration of analgesia is subject to cultural and social influence. Whether this FBM regimen will provide a mean duration of more than four hours in other study populations needs further investigation.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Yeh, H.-M. Articles by Tsai, S.-K. Search for Related Content PubMed PubMed Citation Articles by Yeh, H.-M. Articles by Tsai, S.-K. Related Collections Obstetrics Regional Anesthesia