A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India

Grace Maria George; Shaloo Ipe; Leena Rachel Koshy; Deepak Mathew Gregory; S Rakhee; Saramma P Abraham

doi:10.4103/2249-4472.132820

ORIGINAL ARTICLE

Year : 2014 | Volume : 4 | Issue : 1 | Page : 29-34

A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India

Grace Maria George¹, Shaloo Ipe², Leena Rachel Koshy², Deepak Mathew Gregory², S Rakhee², Saramma P Abraham²
¹ Department of Cardiac Anaesthesiology, Lisie Hospital, Kochi, Kerala, India
² Department of Anaesthesiology, Malankara Orthodox Syrian Church Medical College, Kolenchery, Kerala, India

Date of Web Publication

20-May-2014

Correspondence Address:
Shaloo Ipe
Department of Anaesthesiology, Malankara Orthodox Syrian Church Medical College, Kolenchery, Kerala - 682 311
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2249-4472.132820

Abstract

Context: The study was to compare the analgesic efficacy of three different epidural solutions - ropivacaine, ropivacaine fentanyl mixture, and ropivacaine buprenorphine mixture - for cesarean section.
Materials and Methods: This was a prospective, randomized, controlled, double blind study carried out in primi parturients undergoing elective cesarean section with singleton fetus. A total of 102 parturients in the age group of 20-35 years, American Society of Anesthesiologists (ASA) I or II scheduled for elective cesarean under continuous epidural anesthesia were divided into three groups using a computer-generated random number list. The test dose (3 ml 2% lignocaine with 15 μg adrenaline) and 0.75% ropivacaine 12 ml were given to all parturients. In addition, normal saline 1 ml, fentanyl 50 μg, and buprenorphine 300 μg were given to Group I, II, and III respectively. Sensory block, motor block, analgesia, maternal effects, fetal outcome, and surgeons' and parturients' satisfaction were evaluated.
Results: Onset of sensory block was faster in the fentanyl and buprenorphine groups compared to ropivacaine group (9.94 ± 0.48, 10.72 ± 0.26 versus 14.59 ± 0.34). Duration of sensory block was prolonged in buprenorphine group as compared to fentanyl and ropivacaine groups (120.41 ± 4.31) versus (95.68 ± 3.28, 98.28 ± 3.42). Duration of analgesia was prolonged in buprenorphine group compared to fentanyl and ropivacaine groups (516.38 ± 29.14 versus 327.06 ± 12.41, 285.78 ± 10.10). It proved to be safe for mother and fetus. The surgeon and the parturients were satisfied with the mode of anesthesia.
Conclusion: Ropivacaine 0.75%, ropivacaine 0.75% with fentanyl 50 mg, or buprenorphine 300 mg provided safe anesthesia when given extradurally for cesarean section. Addition of both fentanyl and buprenorphine to ropivacaine hastened the onset of sensory block, while addition of buprenorphine provided prolonged excellent postoperative analgesia.

Keywords: Buprenorphine, extradural, fentanyl, obstetric anesthesia, ropivacaine

How to cite this article:
George GM, Ipe S, Koshy LR, Gregory DM, Rakhee S, Abraham SP. A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India. J Obstet Anaesth Crit Care 2014;4:29-34

How to cite this URL:
George GM, Ipe S, Koshy LR, Gregory DM, Rakhee S, Abraham SP. A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India. J Obstet Anaesth Crit Care [serial online] 2014 [cited 2023 Mar 27];4:29-34. Available from: https://www.joacc.com/text.asp?2014/4/1/29/132820

Introduction

Extradural anesthesia with local anesthetic alone or in combination with opioids is an established anesthetic technique for cesarean section. ^[1],[2] Ropivacaine is a long-acting amide local anesthetic. Between ropivacaine and bupivacaine, onset and duration of sensory block is comparable and the motor block less with ropivacaine when equal concentrations are used. ^[3],[4],[5] Administration of opioids to the local anesthetic has been shown to accelerate the onset, enhance the quality, and prolong the duration of blockade. ^[6],[7],[8] Cherng et al., ^[8] in his study showed the hastening of anesthesia with the addition of fentanyl to lidocaine in epidural anesthesia. Kawamoto et al., ^[10] and Agarwal et al., ^[11] proved the efficacy of buprenorphine given intrathecally and epidurally in cesarean section and labor analgesia. Only limited data is available for the use of ropivacaine and effect of adding opioids to ropivacaine in extradural anesthesia for cesarean section. The present study compared the effect of addition of fentanyl or buprenorphine to ropivacaine 0.75% when administered extradurally for cesarean sections.

Material and methods

A prospective, randomized, double blind study was conducted with the approval of hospital's ethics committee. Informed written consent was obtained from all parturients. The primary end point of the study was taken as the duration of analgesia. By using G Power (3.1) software analysis, it was found that in order to ensure a power of 90% at a significance level of 0.05, a sample size of 25 per group was sufficient. A total of 102 parturients of category American Society of Anesthesiologists (ASA) I and II, aged 20-35 years with a singleton fetus posted for elective cesarean section were divided into three groups using computer-generated random number list. To ensure blinding, the test drug was prepared by an independent anesthesiologist who did not take part further in the study. The study drug was the same volume (13 ml) in all the groups. Anesthesiologist conducting the study, the surgeon, the patient, and the neonatologist assessing the neonatal outcome were blinded to the study drug used. Exclusion criteria for extradural anesthesia included local sepsis, coagulopathy, and neurological deficit.

Parturients were fasting for 6 h and were premedicated with oral ranitidine (150 mg) and ondansetron (4 mg) 1 h before anesthesia. Electrocardiogram (ECG), blood pressure (BP), and oxygen saturation were monitored using a multiparameter monitor. Injection midazolam 1 mg was given intravenously 5 min before the epidural and parturients were co-loaded with 750 ml of Hartman's solution during the epidural. Extradural block was performed in the lateral decubitus position at L3-L4 or L4-L5 space with an 18 gauge Touhy needle using midline approach. Extradural space was identified by loss of resistance to air technique. After negative aspiration for blood and cerebrospinal fluid (CSF), extradural catheter was threaded in a cephalic direction so that 3 cm of the catheter was in the space. Test dose of 3 ml 2% lignocaine with 15 mg adrenaline was given to confirm the catheter position. After 3 min, the test drug 12 ml of 0.75% ropivacaine was given in all the groups. In addition saline 1 ml, fentanyl 1 ml (50 mg), and buprenorphine 1 ml (300 mg) was given in Groups I, II, and III, respectively. A left uterine displacement of 15° was maintained. Oxygen was supplemented through a face mask.

Baseline ECG, BP, and oxygen saturation were recorded before the procedure. These parameters were monitored at 5 min interval during anesthesia and subsequently at 30 min interval for 24 h postoperatively. Fetal heart rate was monitored by external cardiotocography until the time of surgery. Sensory block was tested by pin prick using 26 gauge hypodermic needle initially at 5 min and then at 3 min interval till the maximum level achieved was confirmed, and there after every 10 min till the sensory block regressed by two levels. Duration of sensory block was defined as the time interval between the maximum levels of sensory block achieved, to the time of regression of block by two segments. Incision was made when the sensory block reached T6. Induction to delivery time (ID interval) and uterine incision to delivery time (UD interval) were recorded. Oxytocin 15 units were given as infusion after delivery of the baby. Motor block was assessed at 5 min interval according to Bromage Scale. Duration of motor block was defined as the time of absence of knee flexion to return of knee flexion. Sedation was assessed intra- and postoperatively for 24 h using the sedation score (0-eyes open spontaneously, 1-eyes open on verbal stimulation, 2-eyes open on physical stimulation, and 3-unarousable) and the highest score achieved was taken into consideration. Hypotension was taken as systolic BP ≤100 mmHg. Heart rate of ≤50 and ≥140 was considered abnormal. Hypotension was initially treated with rapid infusion of fluid. Intravenous ephedrine was supplemented if the systolic BP persisted below 100 mmHg for a period of 1 min. Bradycardia was treated with 0.6 mg atropine intravenously. Criteria for respiratory inadequacy were taken as an oxygen saturation ≤94%, a respiratory rate ≤12/min or the need to support ventilation. Neonatal outcome was evaluated by the neonatologist who was blinded to the study drug. Apgar score at 5 min ≤7 and umbilical arterial pH of ≤7.2 were taken as abnormal. The overall quality of anesthesia was judged by the surgeon and patient on a numerical rating scale (NRS) from 1 unsatisfactory to 10 excellent). Postoperatively, parturients were monitored in the post-anesthesia care unit (PACU) for 24 h. Total duration of analgesia was calculated from onset of sensory block (T6) to end of analgesia, that is, pain score of 3 or more on the verbal NRS (0-no pain, 2-4 mild pain, 57 moderate pain, 8-10 worst pain). Incidence of nausea, vomiting, pruritus, and sedation was observed for 24 h postoperatively. Nausea and vomiting was assessed on a 3-point scale (0-none, 1-nausea alone, 2-nausea and vomiting) Urinary retention was not assessed as all parturients were catheterized for 24 h.

Statistical analysis

Data was analyzed using Statistical Package for Social Sciences (SPSS) version 21. All continuous variables are presented as mean ± standard error. A P-value of <0.001 was considered as statistically significant.

Results

Out of the 102 parturients randomized into the study, seven were excluded due to various reasons (2-inadequate block requiring conversion to general anesthesia, 4-lack of completion of data, 1-accidental dural puncture, etc.). The remaining parturients were analyzed; 32 in Group I, 29 in Group II, and 34 in Group III. The data was compared using analysis of variance (ANOVA; F-test) [Table 1].

Table 1: Patient characteristics (mean ± SE)

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The groups were comparable in ASA grading, age, height, weight, baseline BP, pulse rate, respiratory rate, and oxygen saturation [Table 2]a and b].

Post hoc analysis was carried out using Tukey' honestly significant difference (HSD) where there was significant difference in the parameters in the initial analysis. Comparison was made between plain ropivacaine and fentanyl and buprenorphine groups and also between fentanyl and buprenorphine groups.

Onset of sensory block was faster in the fentanyl and buprenorphine groups compared to ropivacaine group (9.94 ± 0.48, 10.72 ± 0.26 vs 14.59 ± 0.34), but there was no difference between fentanyl and buprenorphine groups (-0.783, 0.328). Duration of sensory block was prolonged in buprenorphine group as compared to fentanyl and ropivacaine groups (120.41 ± 4.31) versus (95.68 ± 3.28, 98.28 ± 3.42). There was no difference between fentanyl and ropivacaine groups (2.605, 0.864). Duration of analgesia was prolonged in buprenorphine group compared to fentanyl and ropivacaine groups (516.38 ± 29.14 vs 327.06 ± 12.41, 285.78 ± 10.10). There was no difference between fentanyl and ropivacaine groups (41.278, 0.752) [Figure 1].

Figure 1: Comparison of duration of analgesia

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In the fentanyl and buprenorphine groups, more than 75% of the parturients achieved a higher sensory level (T4 or higher). In the buprenorphine group, 80% of the parturients had analgesia at 6 h and 25% at 12 h.

The BP, pulse rate, respiratory rate, and oxygen saturation of all the parturients were within acceptable limits intraoperatively and postoperatively and were comparable between the groups. Three parturients in plain ropivacaine group, two parturients in fentanyl group, and two parturients in buprenorphine group had transient hypotension (BP <100 mmHg systolic), which was managed with single dose of 6 mg ephedrine intravenously and a rapid infusion of intravenous fluids. No patient had extremes of heart rate (bradycardia or tachycardia). Oxygen saturation and respiratory rate were within normal limits. Apgar score at 5 min was above 7 and umbilical cord arterial blood pH was above 7.2 in all the neonates. No one required mechanical ventilation, tracheal intubation, or admission to intensive care unit (ICU) denoting an acceptable neonatal outcome. There was no incidence of nausea or vomiting. Pruritus not needing any intervention was observed in two parturients (6.3%) in fentanyl group. Urinary retention could not be assessed as all parturients were catheterized. Sedation score appeared to be within 1 (arousable on verbal stimulation) in all the three groups. NRS scores denoting surgeons' and parturients' acceptability of the anesthetic was 7 or more [Table 3].

Table 2:

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Table 3: Maternal and fetal effects and acceptability of the three groups

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Discussion

In the present study, ropivacaine (0.75%) and ropivacaine (0.75%) with fentanyl (50 μg) and buprenorphine (300 μg) given extradurally provided effective anesthesia for cesarean section. In the fentanyl and buprenorphine groups, onset of sensory block was earlier, the duration prolonged, and the level of block higher than that observed in the ropivacaine group. This was similar to the observation by Hong et al., ^[12] in their study. A faster onset of sensory block with opioids is advantageous in the case of an urgent cesarean section where extradural anesthesia is not otherwise preferred as it is thought to take more time to be effective. The sensory block and the duration of analgesia was maximum in the buprenorphine group (80% of parturients having analgesia at 6 h and 25% at 12 h) delaying the need of supplemental analgesia in the postoperative period. A study by Ipe et al., ^[13] reported the safety and prolonged analgesia of buprenorphine given in combination with bupivacaine intrathecally or extradurally.

The combination of local anesthetic and opioids may effectively inhibit multiple areas of neuronal excitability. One of the possible mechanisms of opioid-induced acceleration of sensory block is its property of blocking nerve conduction in spinal roots. There are also synergistic interactions between local anesthetics and opioids. ^[14],[15] This explains the fast onset and prolonged duration of sensory block in the opioid group. Motor block (onset and duration) was similar in all the groups as expected which corresponds to the observation by Dallel et al., in his study. ^[15] The motor block achieved was adequate to provide good surgical conditions as denoted by the surgeons' assessment.

The main concern about using a drug in pregnancy is its safety profile on the mother and the fetus. The classical side effects of concern about neuraxial opioids are depression of ventilation, sedation, pruritus, nausea and vomiting, and urinary retention; out of which respiratory depression is the most serious. Opioids migrate through CSF and produce respiratory depression by acting on respiratory center. The occurrence of respiratory depression after systemic administration of buprenorphine has been reported. ^{[16],[17],[18]} The possibility of immediate and late respiratory depression with buprenorphine administered epidurally has been a cause of concern for using the drug via the epidural route. Studies on compatibility with tissue and CSF indicate that buprenorphine may be administered safely epidurally. In contrast to morphine, epidural buprenorphine is absorbed by lipids of the surrounding tissues so well that its concentration is too low to cause depression when it reaches the respiratory centers. So the risk of late respiratory depression with epidural buprenorphine is very low. ^[19] Varying doses of buprenorphine (60, 150, and 300 μg) has been used in combination with local anesthetics for epidural anesthesia and analgesia. When 300 μg of buprenorphine was used as against lower doses, the analgesia was prolonged without causing any untoward effect on the mother or fetus as shown in the studies by Lam et al., and Ipe et al. ^[13],[20] A higher dose of buprenorphine (300 μg) used epidurally in this study provided prolonged postoperative analgesia without causing any respiratory inadequacy or other complications in the mother or fetus. Maternal adverse events were evenly distributed across treatment groups, the most common being transient hypotension which was mild. In our observation, only a small number in the fentanyl group had pruritus of mild nature. Pruritus is generally mild and is more likely to occur in parturients due to the interaction of estrogen with opioid receptors, but it can occasionally be very distressing to the patient and may require pharmacologic intervention. Nausea and vomiting was not reported. Nausea and vomiting induced by neuraxial opioids are likely to be the result of cephalad migration of the drug in CSF and subsequent interaction with opioid receptors located in the area postrema. The low incidence of pruritis and absence of nausea and vomiting seen in our study even in the buprenorphine group is in contrast to the high incidence reported in various studies in parturients. This could be due to the fact that all the parturients received ondansetron (an antipruritic and antiemetic) preoperatively and round the clock in the postoperative period and also due to the prompt treatment of hypotension. ^[21] Ondansetron is said to be effective in pruritis caused by hydrophilic opioids. ^[21] Sedation, if at all it occurred was mild. Safety of the neonate was established. The surgeon's and the patient's acceptability of the anesthetic was good. One limitation of this study was that, urinary retention could not be assessed as the parturients were catheterized for 24 h postoperatively.

In conclusion, ropivacaine 0.75%, ropivacaine 0.75% with fentanyl, and ropivacaine 0.75% with buprenorphine provided adequate safe anesthesia when given extradurally for cesarean section. Addition of opioids to ropivacaine hastened the onset and prolonged the sensory block. Buprenorphine provided prolonged excellent postoperative analgesia.

Acknowledgement

Department of Gynaecology and Obstetrics, who allowed us to conduct the study on their patients.

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