A randomized clinical study comparing spinal anesthesia with isobaric levobupivacaine with fentanyl and hyperbaric bupivacaine with fentanyl in elective cesarean sections.

BACKGROUND: To date, racemic bupivacaine is the most popular local anesthetic for spinal anesthesia in parturients undergoing elective cesarean delivery. With the introduction of levobupivacaine as pure S (-) enantiomer of bupivacaine which offers advantages of lower cardiotoxicity and neurotoxicity and shorter motor block duration, its use has widely increased in India. However, very few studies have been conducted about its efficacy in obstetric anesthesia. Thus, this study was undertaken to compare the sensorial, motor block levels, and side-effects of equal doses of hyperbaric bupivacaine and levobupivacaine with intrathecal fentanyl addition in elective cesarean cases.
MATERIALS AND METHODS: After approval of College Ethical Committee, 30 parturient with American Society of Anesthesiologists I-II undergoing elective cesarean section were enrolled for study with their informed consent. They were randomly divided equally to either Group BF receiving 10 mg (2 ml) hyperbaric bupivacaine and 25 mcg (0.5 ml) fentanyl, or Group LF receiving 10 mg (2 ml) isobaric levobupivacaine and 25 mcg (0.5 ml) fentanyl. Sensory and motor block characteristics of the groups were assessed with pinprick, cold swab, and Bromage scale; observed hemodynamic changes and side-effects were recorded. Effects on the neonate were observed by APGAR score at 1 and 5 min and umbilical cord blood gas analysis.
RESULTS: Hemodynamic parameters like mean arterial pressure of Group BF were found to be lower. Group BF exhibited maximum motor block level whereas in Group LF, max sensorial block level and postoperative visual analog scale scores were higher. Umbilical blood gas pCO2 was slightly higher, and pO2 was marginally lower in Group BF. Onset of motor block time, time to max motor block, time to T10 sensorial block, reversal of two dermatome, the first analgesic need were similar in both groups.
CONCLUSION: Intrathecal isobaric levobupivacaine-fentanyl combination is a good alternative to hyperbaric bupivacaine-fentanyl combination in cesarean surgery as it is less effective in motor block, it maintains hemodynamic stability at higher sensorial block levels.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Spinal administration of local anesthetics is a preferred technique for cesarean section (CS) as it produces analgesia, anesthesia, and motor block. However, this effect depends upon the volume, concentration, and doses of the drug used.[12] 0.5% hyperbaric bupivacaine is more commonly used for spinal anesthesia for CS.[3] Although hyperbaric local anesthetic solutions have a remarkable record of safety, their use is not totally without risks.[456] To prevent unilateral or saddle blocks, patients should move from the lateral or sitting position rapidly and after mobilization of the patients, extension or early return of the block may be seen. Hyperbaric solutions may cause sudden cardiac arrest after spinal anesthesia because of the extension of the sympathetic block.[78] The use of truly isobaric solutions may prove less sensitive to position issues. Hyperbaric solutions may cause hypotension or bradycardia after mobilization, isobaric solutions are favored with respect to their less sensitive to position change properties.[9]

Recently, levobupivacaine, the pure L (−) enantiomer of bupivacaine, is preferred during spinal anesthesia due to its lower cardiovascular side-effects and central nervous system toxicity.[10111213] The plain levobupivacaine has also been shown to be truly isobaric with respect to cerebrospinal fluid (CSF) of pregnant women.[1415] Its use in this setting may offer special advantages because this property may translate to a more predictable spread.

The addition of low doses of opioids to local anesthetics during spinal anesthesia for CS decreases the incidence of local anesthetic related side-effects, reduces the time of onset of the anesthetic effect, and increases the quality of intra- and post-operative analgesia by reducing the administered dose of the local anesthetic.[16]

Fentanyl can be combined with local anesthetics for spinal anesthesia and when used in this way it prolongs the duration of action and spread of sensory block as well.[17] Fentanyl has been combined with bupivacaine for lower limb surgery and also for inguinal herniorrhaphy and CS.[17181920]

We planned to compare the onset and duration of action, levels of sensory and motor blocks and side-effects of equal doses of hyperbaric bupivacaine and levobupivacaine with intrathecal fentanyl addition in spinal technique in elective cesarean cases. Our aim was to compare the efficacy of low-dose local anesthetics used together with opioid to decrease side-effects associated with these local anesthetics.

MATERIALS AND METHODS

After Institutional Ethical Committee approval and informed consent were obtained, 30 women scheduled for elective cesarean delivery, of more than 37 weeks gestation, American Society of Anesthesiologists physical status class I or II, were enrolled into this prospective randomized, double-blind study.

Patients refusing regional anesthesia, having contraindications to spinal anesthesia, those with a body weight over 100 kg, shorter than 150 cm and taller than 175 cm, those who received medications other than perinatal vitamin, calcium, protein and iron preparations, having systemic diseases, expectant mothers with fetal anomaly, placenta previa, abruptio placenta were excluded from the study.

Following application of routine monitors (noninvasive blood pressure [BP] measurement, electrocardiography, and pulse oximetry) and insertion of a peripheral 18-gauge intravenous (IV) cannula, a rapid infusion of lactated Ringer's solution 15 ml/kg was administered. Baseline systolic BP (SBP) and heart rate were calculated as the mean of the three recordings. Patients were placed in the left lateral position. After disinfecting the skin and infiltrating with 2% lidocaine, lumbar puncture was performed at the L3-4 interspace using a 25-gauge Quincke spinal needle. Patients were randomly divided into two groups. For Group LF (n = 15); 10 mg 0.5% (2 ml) plain levobupivacaine + 25 μg (0.5 ml) fentanyl, for Group BF (n = 15); 10 mg 0.5% (2 ml) hyperbaric bupivacaine + 25 μg (0.5 ml) fentanyl, being a total of 2.5 cc, administered intrathecally within 10 s. Subsequently, patients were turned to the supine position. Oxygen 4 L/min was administered via a facial mask. The sensory level of spinal anesthesia was assessed bilaterally in the midclavicular line by pinprick, using a short beveled 25-gauge needle and cotton swab, and was recorded at baseline prior to spinal injection, then every minute for the first 15 min after injection, and every 5 min till end of the surgery. BP, heart rate, and the extent of motor block were recorded at the same measurement intervals. Permission to perform the operation was given once a T4-T6 level had been achieved. Considering the time of intrathecal injection as time 0, the time to onset of sensory block, the time taken to reach maximum sensory block level, the time to regression of two dermatomes of the sensory block, the duration of the regression of the sensory block level to T12 from the maximum level was recorded. The level of motor block was assessed with modified Bromage scale (0 = no paralysis, able to flex hips/knees/ankles; 1 = able to move knees, unable to raise extended legs; 2 = able to flex ankles, unable to flex knees; 3 = unable to move any part of the lower limb). The time of onset of motor block, the time to reach Bromage 3 and the time of complete disappearance were recorded.

Neonatal outcome was assessed by the APGAR score and umbilical cord blood gas analysis. Postoperatively vital signs, sensory and motor blockade assessed every 30 min for 3 h and at 4th, 8th, 12th, and 24th h.

Bradycardia was defined as pulse rate <50 bpm, and it was treated with 0.6 mg IV atropine. IV boluses of 6 mg ephedrine and additional IV fluids were administered to treat hypotension, which was defined as SBP below 90 mmHg or a decrease systolic pressure of >30% from the baseline value. The amount of ephedrine used for each patient was recorded. Whether there was a need for intraoperative analgesia and time to first rescue analgesic requirement in the postoperative period were recorded and the planned treatment included 75 mg diclofenac IV infusion in postoperative time period. Intraoperative and postoperative nausea and vomiting and other side-effects were recorded.

RESULTS

In the present study, the anesthetic effects of plain levobupivacaine + fentanyl and hyperbaric bupivacaine + fentanyl were compared in patients who were scheduled for CS under spinal anesthesia. There was no statistically significant difference between the two study groups in terms of demographic characteristics and duration of the operation [Table 1].

Table 1

Demography

The onset of sensory block and the time for the sensory block to reach T10 was shorter in Group BF whereas the time for regression of two dermatomes was longer in Group BF. The time of onset of motor block in Group BF was significantly shorter than Group LF. However, complete motor block was obtained within 15 min in all patients in both groups (Bromage 3). Motor block developed faster and lasted longer with the hyperbaric bupivacaine [Table 2].

Table 2

Characteristics of anesthesia

Hypotension and bradycardia were more common with hyperbaric bupivacaine seen in 2/3rd and 1/3rd of the patients, respectively. In addition, nausea was noticed more frequently with hyperbaric bupivacaine. Other side-effects such as headache, backache, itching, vomiting, and shivering were almost similar in both the groups [Table 3].

Table 3

Side-effects

Hemodynamic stability was better with levobupivacaine compared to hyperbaric bupivacaine [Table 4]. Fall in mean arterial pressure in Group BF was considerable with about 6 patients requiring ephedrine to stabilize the hemodynamics.

Table 4

Hemodynamic parameters of the levobupivacaine and bupivacaine groups

APGAR scores at 1 min and 5 min and umbilical cord gas analysis [Table 5] showed no significant difference between the two groups. These data were within physiological ranges in Group LF and Group BF.

Table 5

Neonatal effects

DISCUSSION

In this present study, levobupivacaine and hyperbaric bupivacaine combined with fentanyl produced a similar quality of sensorial blockade as well as maternal hemodynamic and neonatal effects in CS under spinal anesthesia. Combination of fentanyl with levobupivacaine induced less motor blockade than hyperbaric bupivacaine when administered via the intrathecal route.

The efficacy of neuraxial local anesthetics is enhanced by the addition of intrathecal opioids. Such combinations are usually associated with improved anesthesia and analgesia. It also allows the use of very low doses of local anesthetic, which contributes to more stable hemodynamics.[212223]

In a study by Goel et al.,[24] intrathecal fentanyl added to low-dose local anesthetics produces a synergistic effect without increasing sympathetic blockade or delaying discharge from hospital.

Lee et al. study[25] was published as the first study on the intrathecal use of 0.5% levobupivacaine with fentanyl. They concluded that 2.3 ml of 0.5% levobupivacaine with fentanyl (15 μg) was as effective as 2.6 ml of 0.5% levobupivacaine alone in spinal anesthesia for urological surgery. Significant differences were not observed between the two groups with respect to hemodynamic changes and the quality of sensory and motor blockades.

In a recent study by Cuvas et al.,[26] addition of fentanyl 15 μg (0.3 ml) to 0.5% levobupivacaine (2.2 ml) produced a shorter duration of motor blockade than pure 0.5% levobupivacaine (2.5 ml solution) in spinal anesthesia, whereas both regimens were effective for transurethral resections. Akcaboy et al.[27] and Hakan Erbay et al.[28] compared the effectiveness of low-doses of 0.5% levobupivacaine and 0.5% bupivacaine (5 mg and 7.5 mg, respectively) when combined with fentanyl (25 μg). These regimens were shown to be effective in spinal anesthesia for transurethral resection of the prostate if used in higher doses. In both studies, levobupivacaine plus fentanyl resulted in effective sensorial blockade with less motor blockade than bupivacaine plus fentanyl.

Studies have demonstrated the effect of a combination of local anesthetic and opioid for regional anesthesia in CS both extradurally[12029] and intrathecally;[19303132333435] different results with regard to the characteristics of sensorial blockade between levobupivacaine and bupivacaine have been observed. However, most of these studies have concluded that there was less motor blockade with levobupivacaine than with bupivacaine.

In the present study, decreases in SBP and diastolic blood pressure as well as changes in heart rate were in acceptable ranges. Erdil et al.[33] noted, in spinal anesthesia, better hemodynamic stability associated with low-dose levobupivacaine plus fentanyl compared with that seen with low-dose bupivacaine plus fentanyl. Coppejans and Vercauteren[29] compared equipotent doses of bupivacaine, levobupivacaine, and ropivacaine combined with sufentanil in patients undergoing elective CS with combined spinal–epidural anesthesia. They found that hemodynamic values were comparable between the three groups (although a trend towards better SBPs and a lower prevalence of severe hypotension were noticed with levobupivacaine). In the present study too, maternal hemodynamics were stable with levobupivacaine when compared with hyperbaric bupivacaine.

Hypotension was the most common side-effect seen in about 50% of parturients in this study (26.67% in levobupivacine and 66.67% in bupivacine) during spinal anesthesia. This is due to engorgement of epidural veins from aortocaval compression in a pregnant woman with displacement of CSF, which may contribute to unwanted cephalad extensions of the blockade, which can be associated with an increased risk of hypotension. In the present study, the relatively higher prevalence of hypotension in both groups can be attributed to the high dose of the local anesthetics. Itching was recorded in both groups which is commonly reported with intrathecal use of fentanyl.[27]

In the present study, the neonatal effects of levobupivacaine and bupivacaine in combination with fentanyl were similar. In a study by Lirk et al.,[34] intrathecal bupivacaine, ropivacaine, and levobupivacaine used for CS produced similar effects on neonates (as evaluated by APGAR scores and the pH of arteries in the umbilical cord). In another study,[29] after combination of sufentanil with bupivacaine, ropivacaine, and levobupivacaine, APGAR scores and the pH of arteries in the umbilical cord in neonates did not differ; our results are consistent with that study.

In the present study, we preferred to use 10 mg of 0.5% levobupivacaine and 0.5% hyperbaric bupivacaine in combination with 25 μg fentanyl for spinal anesthesia for patients undergoing CS. Levobupivacaine produced adequate and comparable sensorial blockade with bupivacaine but induced less motor blockade than bupivacaine, a result consistent with previous studies.

The only study comparing the combination of fentanyl and levobupivacaine versus bupivacaine in CS similar to our study protocol is that of Guler et al.[35] They compared fixed doses of intrathecal 0.5% levobupivacaine (10 mg) and 0.5% hyperbaric bupivacaine (10 mg) combined with intrathecal fentanyl (25 μg) in terms of the characteristics of sensory and motor blockade in parturients undergoing elective CS with spinal anesthesia. In that study, levobupivacaine exhibited advantage of significantly shorter and less pronounced motor blockade along with better hemodynamic stability than racemic bupivacaine.

Guler et al.[35] compared 2 ml and Subaşı et al.[36] and Turkmen et al.[37] compared 1.5 ml of drug with opioid adjuvant and observed no significant difference in terms of maximum distribution, and durations of sensory and motor block [Table 6].

Table 6

Comparison anesthetic properties with similar studies

In present study, hyperbaric bupivacaine showed faster onset of sensory block and longer duration of sensory block which is consistent with findings of above studies.

Similarly, the development of motor block was faster and lasted longer with hyperbaric bupivacaine which was again similar to observations of Guler et al., Subaşı et al., and Turkmen et al.

Guler et al. reported that levobupivacaine, compared with bupivacaine, causes less bradycardia, and hypotension which is also observed in our study. Turkmen et al. stated that excluding hemodynamic adverse effects, bupivacaine, and levobupivacaine share similar adverse effect pattern.

CONCLUSION

In conclusion of our study, we would like to state that both levobupivacaine and hyperbaric bupivacaine provide fast and effective induction of surgical anesthesia for elective CS with no adverse effects on neonates. However, combination of levobupivacaine and fentanyl offers shorter motor block time, decreases the incidence of adverse effects such as hypotension and bradycardia, and provides a better hemodynamic stability thus minimizing the risk and providing early mobility. Therefore, the combination of levobupivacaine with fentanyl should be preferred alternative for elective CSs.