Levobupivacaine for labor analgesia.

BACKGROUND: Combined spinal-epidural analgesia has become the preferred technique for labor analgesia as it combines the benefits of both spinal analgesia and flexibility of epidural catheter. Study was carried out with the primary aim to compare levobupivacaine and ropivacaine with fentanyl in terms of onset and duration of sensory block and to know maternal and fetal outcome.
MATERIALS AND METHODS: In a prospective randomized double-blind study, 60 primipara of the American Society of Anesthesiologists health status Class I and II with singleton pregnancy in active stage of labor were randomly allocated into two groups of 30 each. Group A received 3 mg intrathecal levobupivacaine with 25 μg fentanyl followed by epidural top-ups of 14 ml of levobupivacaine 0.125% with fentanyl 30 μg whereas Group B received 4 mg intrathecal ropivacaine with 25 μg fentanyl followed by epidural top-ups of 14 ml of ropivacaine 0.2% with fentanyl 30 μg. Patients were monitored for sensory and motor block characteristics, hemodynamics, maternal and fetal outcome, side effects, and complications. These characteristics were analyzed using the "Chi-square tests" and "unpaired t-test."
RESULTS: Onset of analgesia was rapid in Group A (4.72 ± 0.54 min) as compared to Group B (5.58 ± 0.49 min). Duration of analgesia was also prolonged in Group A (117.00 ± 11.86 min) as compared to Group B (90.17 ± 8.85 min). Patients remained hemodynamically stable and side effects, and complications were comparable in both groups.
CONCLUSION: Levobupivacaine with fentanyl leads to early onset and prolonged duration of analgesia as compared to ropivacaine with fentanyl during labor analgesia.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Labor pain can be regarded as the most severe kind of pain.[1] It results in a stress response in the mother and various disorders of labor such as maternal hypertension, dystocia, and meconium staining.[2] Hence, providing effective labor analgesia can benefit not only the mother but her neonate also.

Various methods can be used for labor analgesia but combined spinal-epidural (CSE) technique is gaining increasing popularity in recent years[3] because intrathecal component provides rapid onset of analgesia and the epidural component provides the flexibility of providing unlimited duration of analgesia. Advantages of both spinal and epidural techniques are combined in CSE technique without much increase in the incidence of complications.[4]

Various local anesthetics can be used either alone or combination with opioids in this technique. Bupivacaine was most commonly used but concerns about its cardiac toxicity and intensity of its motor block have led to the development of newer drugs such as levobupivacaine and ropivacaine.[56] Addition of opioids has synergistic effects as they act directly on opioid receptors in the spinal cord and help reduce the dose of local anesthetic required thus reducing their toxicity.[4] Various opioids that have been used for labor analgesia include morphine, meperidine, sufentanil, and fentanyl.[7] Fentanyl has the advantage of low cost, rapid onset, and relatively long duration of analgesia without significant motor blockade. However, it is also true that addition of opioids can be associated with pruritus, nausea and vomiting, fetal bradycardia, urinary retention, and maternal respiratory depression.[8]

Our primary aim of this study was to compare levobupivacaine and ropivacaine with fentanyl in terms of onset and duration of sensory and motor block after intrathecal dose, maternal and fetal outcome, side effects and complications, and maternal satisfaction score. In our study, we assumed that levobupivacaine is 1.31 times more potent than ropivacaine based on the study done by Sia et al.[9]

MATERIALS AND METHODS

After approval from the Hospital Ethics Committee and obtaining written informed consent, 60 full-term primigravida of the American Society of Anesthesiologists (ASA) health status Class I and II with singleton pregnancy and vertex presentation in the active stage of labor (cervical dilatation of >3 cm) were randomly allocated into two groups of 30 each.

Group A received 3 mg of isobaric levobupivacaine with 25 µg fentanyl intrathecally followed by epidural top-ups of 14 ml 0.125% isobaric levobupivacaine and 30 µg fentanyl making total volume of 15 ml.

Group B received 4 mg isobaric ropivacaine with 25 µg fentanyl intrathecally followed by epidural top-ups of 14 ml 0.2% isobaric ropivacaine and 30 µg fentanyl making total volume of 15 ml.

After confirming cervical dilatation of more than 3 cm, baseline heart rate (HR), noninvasive blood pressure, oxygen saturation, respiratory rate, electrocardiogram, and fetal HR were recorded. Baseline pain was also assessed using visual analog scale (VAS) (0 = No pain and 10 = Severe pain). An intravenous line was secured with 18-gauge intracath and parturients were preloaded with ringer lactate 10 ml/kg body weight in 20–30 min. Parturients were placed in left lateral decubitus position and after skin infiltration at the L2-3 or L3-4 interspace, 18-gauge Tuohy needle was advanced slowly into the epidural space using the loss of resistance to air technique. Intrathecal drugs were given using 27-gauge Whitacre spinal needle and then epidural catheter was inserted 3–5 cm into the epidural space. Epidural bolus dose was given when the patient reported two consecutive contractions as being painful or VAS >3.

Sensory block was assessed by loss of sensation to pinprick using 22-gauge blunt hypodermic needle. The onset of analgesia was taken as the onset of sensory block to T10 level and time taken to reach the same was noted. The highest level of sensory block achieved was also noted. Duration of analgesia was taken from intrathecal injection to the time of request of additional analgesia (VAS >3). Grade of motor block was checked using modified Bromage scale (0: full flexion of foot and knee, 1: just able to flex knees and free movement of foot, 2: able to move foot only, and 3: unable to move foot or knee). Onset and duration of motor block were noted.

Continuous hemodynamic monitoring of HR, respiratory rate, noninvasive blood pressure, oxygen saturation, and fetal HR was done. Readings were recorded every 2 min for the first 10 min, thereafter every 5 min until 30 min and then every 15 min until the end of delivery in both groups. Maternal hypotension was defined as a fall in systolic blood pressure of more than 20% from the baseline and was treated by giving additional ringer lactate and if necessary, injection ephedrine was given intravenously.

In case, instrumental delivery was required epidural dose was repeated 15 min before the procedure in both the groups. In those cases where there was evidence of fetal distress or failure to progress due to some obstetrical factors, cesarean section was performed by extending the block with 0.5% levobupivacaine in Group A and 0.5% ropivacaine in Group B.

Side effects and complications were assessed and documented. Obstetric outcome and Apgar scores at 1, 5, and 10 min were recorded. Patient satisfaction score was noted at follow-up visit after 24 h of delivery with a scale; 5 - Excellent, 4 - Very good, 3 - Good, 2 - Fair, and 1 - Poor.

Statistical analysis was performed using “unpaired t-test” for parametric data whereas for nonparametric data “Chi-square test” was used. P <0.05 was considered statistically significant and P < 0.001 was considered statistically highly significant.

RESULTS

Both the groups were comparable with respect to demographic characteristics and baseline hemodynamic parameters [Tables 1 and 2]. Sensory and motor block parameters were recorded [Table 3]. Mean onset of analgesia was rapid in Group A as compared to Group B. The difference between the two groups was statistically highly significant (P < 0.001). The highest sensory level reached by pinprick method was T5 in Group A and T6 in Group B (P < 0.05). The duration of analgesia after the intrathecal dose was longer in Group A as compared to Group B (P < 0.001). The mean numbers of epidural top-ups required in Group A were significantly less as compared to Group B (1.21 ± 0.42 vs. 1.69 ± 0.47, P < 0.001). Motor blockade was measured using modified Bromage scale. Six parturients in group A and five parturients in Group B developed Grade 1 motor block (P < 0.05). Parturients remained hemodynamically stable in both groups. Labor characteristics are shown in Table 4. Instrumental delivery, cesarean delivery rate, and Apgar scores were noted which were similar in both groups (P > 0.05) as shown in Table 5. The incidence of side effects and complications were also comparable between the two groups [Table 6].

Table 1

Patient demographics

Table 2

Baseline parameters

Table 3

Sensory and motor block parameters

Table 4

Labor characteristics

Table 5

Obstetric and neonatal outcome

Table 6

Side effects and complications

DISCUSSION

The American College of Obstetricians and Gynaecologist and the ASA issued a joint statement in 2004 indicating that “maternal request is a sufficient justification for pain relief during labor.”[10] CSE technique combines the advantages of both spinal and the epidural technique. It is increasingly being used these days for labor analgesia. Nowadays, low-dose local anesthetics are being used which selectively blocks the painful stimulus while preserving the motor function.[11]

Till date, there are relatively few studies examining the role of levobupivacaine and ropivacaine for labor analgesia. Both of these drugs were developed in response to reports of cardiotoxicity associated with accidental intravenous bupivacaine administration.[12] In this study, we assumed that levobupivacaine is 1.31 times more potent than ropivacaine based on the study done by Sia et al.[9]

Mean onset of analgesia in Group A was 4.72 ± 0.54 min and in Group B was 5.58 ± 0.49 min. The onset of sensory block in Group A was found to be earlier than in Group B. Mehta et al.,[13] in their study comparing levobupivacaine and ropivacaine 15 mg intrathecally, showed mean onset of sensory block to be 4.38 ± 1.53 min in levobupivacaine group and 5.45 ± 1.00 min in ropivacaine group. Results of our study in terms of mean onset of analgesia are in accordance with the above study.

Duration of analgesia in group A and B is 117.00 + 11.86 and 90.17 + 8.85 mins respectively. Kim et al.,[14] in their study on 60 parturients, comparing 3 mg of ropivacaine and levobupivacaine mixed with 20 µg of fentanyl as a part of CSE technique, showed that intrathecal ropivacaine offered shorter analgesia (87 ± 41 min) as compared to intrathecal levobupivacaine (122 ± 56 min).

Neuraxial analgesia in addition to providing pain relief can cause motor blockade which can lead to inability to bear down by the mother. Use of low-dose local anesthetics these days for labor analgesia has significantly reduced the incidence of motor blockade.[11] None of the parturients had motor impairment before the anesthetic procedure. Motor blockade was measured using modified Bromage scale.[9] 24 (80.00%) parturients in Group A and 25 (83.33%) parturients in Group B had no motor blockade. Six (20.00%) parturients in Group A and 5 (16.67%) parturients in Group B developed Grade 1 motor block only. Motor block grade of 2 or 3 was not observed in either group. The difference between the two groups was statistically nonsignificant (P > 0.05).

Differences in the incidence of side effects and complication between the two groups did not reach statistical significance (P > 0.05). Two (6.67%) parturients in Group A and 1 (3.33%) parturient in Group B developed hypotension. Hypotension responded to intravenous fluid administration. Intravenous ephedrine was not required in any patient. Nausea and vomiting occurred in 4 (13.3%) parturients in both groups. These parturients were given injection ondansetron 4 mg intravenously.

In our study, Apgar score was noted at 1, 5, and 10 min. One baby in Group A and two babies in Group B in our study had Apgar score 7 at 1 min, and no baby had Apgar score <8 at 5 min and 10 min in both groups. P > 0.05 was statistically nonsignificant. The babies who had Apgar score of 7 at 1 min in both groups were resuscitated by suction and oxygenation. In a study done by Purdie and McGrady[15] to compare epidural bolus administration of 0.1% ropivacaine and 0.1% levobupivacaine with 0.0002% fentanyl for analgesia during labor, it has been found that mean Apgar score at 1 min was 9 in both groups.

There are some limitations in this study. First, cord blood pH is an objective retrospective measure of the fetal exposure and response to hypoxia during labor. It could not be done in our set up due to some technical issues. Second, the result of our study could have been more precise if the sample size of study group would have been large, but the patient willing for labor analgesia were limited in our institution.

CONCLUSION

Hence, we conclude that labor analgesia was effective in both the groups but levobupivacaine group is better with respect to rapid onset and longer duration of analgesia compared to ropivacaine group.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.