|Year : 2017 | Volume
| Issue : 1 | Page : 32-36
A comparative study of hyperbaric bupivacaine (0.5%) with hyperbaric levobupivacaine for spinal anesthesia in cesarean section: A randomized, controlled trial
Biswarjit Debbarma, Arunkumar Singh Yumnam, PKS Laithangbam, T Hemjit Singh, T Rupendra Singh, N Ratan Singh
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||17-Jan-2017|
Arunkumar Singh Yumnam
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: None, Conflict of Interest: None
Background: Spinal anesthesia is often used for both elective and emergency cesarean section. One earlier study has shown that intrathecal levobupivacaine given in L 3-4 space did not provide satisfactory intraoperative analgesia in all parturients. We assume that the same dose may work if given in L 2-3 intrathecal space, especially in our population with shorter stature. Materials and Methods: After Institutional Ethical Committee approval, 100 parturients (American Society of Anesthesiologists I-II, aged 18-40 years) and after obtaining written informed consent to received spinal anesthesia for cesarean section were randomized into four groups: Group I (0.5% hyperbaric bupivacaine 7.5 mg in L 2-3 intrathecal space), Group II (0.5% hyperbaric levobupivacaine 7.5 mg in L 2-3 intrathecal space), Group III (0.5% hyperbaric bupivacaine 10 mg in L 3-4 intrathecal space), and Group IV (0.5% hyperbaric levobupivacaine 10 mg in L 3-4 intrathecal space), respectively. Hypotension (systolic blood pressure <100 mmHg or fall >20% from baseline) was treated with injection mephentermine 3 mg intravenous (iv) increment (s). For the ethical reason, inadequate analgesia was treated with 0.5 mg/kg iv ketamine. Statistical analysis was performed using the SPSS version 20 software windows. A P < 0.05 was considered significant. Results: Time to onset of sensory block was faster in 0.5% hyperbaric levobupivacaine 10 mg given in L 3-4 intrathecal space (Group IV P = 0.013). No significant difference was found in time to reach maximum block level (T 4 -T 6 ). Median peak sensory block level was significantly lower in Group II as compared with other group T 6 versus T 4 ; F = 106.159; P < 0.001). Time to regression by two dermatomes was significantly shorter with a lower dose of either bupivacaine or levobupivacaine given at L 2-3 intrathecal space (P = 0.028). The degree of motor block or motor block regression was similar in all the groups. Intraoperative rescue analgesia was required in 20% of patients in Group II (levobupivacaine 7.5 mg in L 2-3 ); it was 4% in each of the remaining groups (P = 0.082). Injection mephentermine used was 24%, 32%, 48%, and 28%, respectively, in Group I to IV though it did not reach statically significance. Conclusion: Levobupivacaine 7.5 mg can be used in lower segment cesarean section when given in L 2-3 space. Onset is faster, and hemodynamic stability is more with levobupivacaine. At the higher dose, the duration of action bupivacaine seems to be longer.
Keywords: Bupivacaine, cesarean section, levobupivacaine, parturients, spinal anesthesia
|How to cite this article:|
Debbarma B, Yumnam AS, Laithangbam P, Singh T H, Singh T R, Singh N R. A comparative study of hyperbaric bupivacaine (0.5%) with hyperbaric levobupivacaine for spinal anesthesia in cesarean section: A randomized, controlled trial. J Med Soc 2017;31:32-6
|How to cite this URL:|
Debbarma B, Yumnam AS, Laithangbam P, Singh T H, Singh T R, Singh N R. A comparative study of hyperbaric bupivacaine (0.5%) with hyperbaric levobupivacaine for spinal anesthesia in cesarean section: A randomized, controlled trial. J Med Soc [serial online] 2017 [cited 2022 May 19];31:32-6. Available from: https://www.jmedsoc.org/text.asp?2017/31/1/32/198439
| Introduction|| |
Spinal anesthesia is often used for both elective and emergency cesarean section. Anesthesia-related mortality is decreased when general anesthesia is avoided.  Following the reports of cardiovascular toxic effects  of bupivacaine by Albrights in 1979, relative pharmacological behaviors of both R(+) and S(−) enantiomers of bupivacaine were studied intensively and the S(−) enantiomer (levo-enantiomer) appeared to have a safer pharmacological profile. 
Levobupivacaine, a pure S(−) bupivacaine enantiomer, was approved by the United States Food and Drug Administration in 1997. While some studies  have found the clinical effect of bupivacaine and levobupivacaine indistinguishable, others  have found levobupivacaine to cause fewer side effects such as hypotension, bradycardia, and nausea. Meanwhile, a recent  study comprising 8 mg of intrathecal bupivacaine with 8 mg of intrathecal levobupivacaine for cesarean section found that levobupivacaine was effective in only 80% compared to 97% of bupivacaine.
In another dose finding study  comprising 7.5, 10, and 12.5 mg of intrathecal levobupivacaine for cesarean section, it was found that 7.5 mg did not provide satisfactory intraoperative analgesia in all parturients. However, these studies , were done in a European population with relatively taller statures, and intrathecal injection was given in L 3-4 interspace. We hypothesized that lower dose might work if given in L 2-3 intrathecal space. Hence, this study was planned in four groups of parturients to compare the effect of two different dosages of bupivacaine and levobupivacaine given in two different intrathecal spaces. Duration of analgesia was planned as the primary outcome, hemodynamic stability, and side effects were assessed as secondary outcomes.
| Materials And Methods|| |
The randomized, clinical trial was conducted in the Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, in 100 parturients (American Society of Anesthesiologists [ASA] I-II, age 18-40 years, heights 135-165 cm) scheduled for elective cesarean section. Following Institutional Ethics Committee approval and after obtaining written informed consent, the parturients were assigned into four groups (n = 25). Groups I and Group II received 7.5 mg of 0.5% hyperbaric bupivacaine and levobupivacaine in L 2-3 intrathecal space, respectively. Group III and Group IV received 10 mg of 0.5% hyperbaric bupivacaine and levobupivacaine in L 3-4 intrathecal space, respectively. Patient refusing regional anesthesia or known contraindication to spinal anesthesia (sepsis, local infection, coagulopathy, spine deformity or space occupying lesion in the brain, maternal hypotension, and hypervolemia) were excluded from the study. Randomization was done by a computer-generated table of random numbers. For blinding, the drugs were prepared by another anesthesiologist not directly involved in the study. Commercially available hyperbaric bupivacaine contain 8% glucose. Levobupivacaine is available as isobaric 0.5% solution. We made it hyperbaric solution  by adding (using insulin needle) 0.32 ml 50% glucose to 2 ml of isobaric levobupivacaine. The specific gravity of cerebrospinal fluid is 0.007. With addition of 8% glucose, specific gravity becomes 1.02487 for bupivacaine and levobupivacaine at 37°C. 
Preanesthetic evaluation was done a day before the scheduled operation for all the parturients. They were asked to take tablet ranitidine 150 mg orally at bedtime. On the day of operation, patients were shifted to the preanesthetic room. A suitable peripheral vein was cannulated with 18-20 G cannula. Injection metoclopramide 10 mg intravenous (iv) and injection ranitidine 50 mg iv were given 1 h prior to shifting to operation theater (OT). Preloading was done with 10 ml/kg of balanced salt solution (Sterofundin, B Braun) within 30 min of spinal anesthesia. At OT baseline, hemodynamics parameters such as noninvasive blood pressure, electrocardiogram , pulse oximetry (SPO 2 ), and heart rate were recorded in the supine position. Then, the patient was put in the left lateral position. Under aseptic and antiseptic precaution, intrathecal injection was given in L 2-3 or L 3-4 space depending on the group assigned (Group I-IV). Time of intrathecal injection was taken as 0 min. Immediately after giving the subarachnoid block, the patient was kept in the horizontal supine position. A wedge was put under the right buttock to avoid aortocaval compression. Then, hemodynamic parameters were recorded for every 1 min for 3 consecutive min, then every 5 min up to 15 min, and then every 15 min interval throughout the surgery period intraoperatively. Hypotension (fall in blood pressure [BP] >20% from the baseline or systolic BP <100 mmHg) was treated with injection mephentermine 3 mg iv increments (s). Bradycardia is defined as HR<50/min and treated with atropine. For the ethical reason, inadequate analgesia was treated with 0.5mg/Kg ketamine to be increased as up to 1mg/Kg, and this does not cause harmful effect on the fetus.  Sensation was checked using pinprick method. Sensory onset time (seconds) was taken as first complain of tingling and numbness in the lower limbs after giving intrathecal injection. Time for sensory block up to T 10 level and up to highest sensory block level, as well as time for sensory regression by two dermatomes and regression up to T 12 level, were recorded. Motor block was assessed using modified Bromage scale  (0 = no paralysis, able to flex hips/knees/ankles; 1 = able to move knees, unable to raise the extended legs; 2 = able to flex ankle, inability to flex knees; and 3 = unable to move any part of the lower limb).
Postoperative hemodynamic changes were recorded for the parturient in the postoperative care unit every 10 min till the patients were stabilized and ready to transfer to respective wards.
Statistical analysis was performed by IBM SPSS for Windows version 20 (Armonk, New York, USA). Two group mean compared by independent sample test (t-test) and more than two group mean by ANOVA (F-test). χ2 -test is applied for categorical variables and the P <0.05 are treated as significant.
| Results|| |
All the patients happen to be female of ASA I. Other demographic variables are also comparable [Table 1].
In [Table 2], we found a significant difference (P = 0.013) in the time to onset of sensory block. This stems mainly from significant differences between Group II and Group IV (t = 3.093 and P = 0.003). Median peak sensory block level is significantly lower in Group II as compared to other groups (T 6 versus T 4 ; P < 0.001). Significant differences (P = 0.028) in the sensory regression time by two dermatomes derived mainly from differences between Group I and Group III (t = 2.707; P = 0.025) and between Group II and Group IV (t = 2.054; P = 0.045). No significant differences in motor block characteristics are seen among the groups.
At a lower dose (7.5 mg in L 2-3 ), there is no difference in the hemodynamic stability between bupivacaine and levobupivacaine. At a higher dose (10 mg in L 3-4 ), levobupivacaine seems to provide more hemodynamic stability than bupivacaine.
Again, within the same drug, the lower dose of either produce more hemodynamic stability than the higher dose [Figure 1].
|Figure 1: Intraoperative five mean systolic blood pressure (mmHg) changes in the four groups with same domain in X-axis against the time in minute in Y-axis. Changes between Group I and III are significant throughout. Changes between Group II and IV are significant from 15 min onward. There is no significant difference between Group I and Group II. Changes between Group III and Group IV were significant only at 10th min (P = 0.049)|
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Rescue analgesia was given in 5 patients out of 25 (20%) in Group II, while it was given only in 4% in each of the remaining groups. Injection mephentermine was given in 24%, 32%, 48%, and 28% of the patients in Group I to Group IV, respectively, for intraoperative hypotension. None of the parturients required injection atropine for significant bradycardia.
| Discussion|| |
This study was undertaken on the premise that intrathecal levobupivacaine 7.5 mg given in L 2-3 intrathecal space may work during lower segment cesarean section (LSCS). This is based on some earlier study  maintaining that intraoperative analgesia with 7.5 mg bupivacaine is inadequate in all the parturients. However, that study was done in some European population with relatively tall stature, and the scenario may be a little different in our population. Hence, we have studied two different doses (7.5 mg versus 10 mg) of bupivacaine and levobupivacaine given in two different intrathecal spaces (L 2-3 versus L 3-4 ). One hundred parturient were divided into four equal (n = 25) groups. The lower dose was given in the higher spaces and the higher dose in the lower spaces.
The results of our study have shown that the sensory onset time (first complain of tingling and numbness on questioning following intrathecal injection) and the time for the sensory block to reach T 10 seems to be faster in the levobupivacaine group. Peak sensory block level is lower in Group II compared to other groups (T 6 versus T 4 ; P < 0.001). Again the sensory regression time by two dermatomes is statically significant (P = 0.028). This is probably not due to the difference in bupivacaine and levobupivacaine per se. As is evident from [Table 2], this is due to increase in dose of either drug. As the dose of local anesthetic is increased, the probability and duration of satisfactory anesthesia are increased, and the time of onset of the block is shortened.  The volume of the anesthetic possibly influences the spread of anesthesia.
Giving the block in the higher space seems to have a more significant effect [P = 0.024; t = 2.329 footnote of [Table 2] in increasing the duration of the block in the case of levobupivacaine compared to bupivacaine. Whether it is a chance finding or related to the segmental distribution of the drug in the spinal cord is unclear. Two earlier studies , also paid not much attention to space of intrathecal injection. Both groups used L 2-3 or L 3-4 space according to their convenience. They assumed that in adult population the height is more dependent on the length of the lower limb bones rather than the length of the vertebral column. This may not be true in our population, and one study  has shown that the spread of local anesthetic in the spinal cord segment will be more in shorter stature.
Considering the pharmacokinetics of the drug,  it seems reasonable to think that the action of bupivacaine will be longer than that of levobupivacaine. The latter is more slowly metabolized by CYP1A2 in the liver and has higher clearance rate (28-37 ml/kg/min). But how those pharmacokinetics affect the metabolism of intrathecally administered drug is unclear. Some studies ,, have found similar effects between levobupivacaine and bupivacaine, while others  have found longer analgesia and increased motor block with bupivacaine. Still others , reported longer analgesia with levobupivacaine. In our study, we cannot find significant differences in the onset and regression of motor block among all the four groups. The reason for these apparent discrepancies in various studies is unclear. The factors which determine the intrathecal spread of local anesthetic agents have been recently reviewed.  It must also be remembered that levobupivacaine solution contains 12.6% more active drugs than those of racemic bupivacaine.  Whatever be the factors, the only modifiable factors available to the clinician are the position of the patient immediately after intrathecal injection, the spread of injection and the baricity of the solution. Some study  give intrathecal injection over 10-15 s and others  give it over 30 s. We have made our solution of levobupivacaine hyperbaric by addition of glucose 80 mg/ml, while some study  use glucose 30 mg/ml. However, one study  has suggested that there is no much change in the specific gravity of cerebrospinal fluid by changing glucose concentration from 30 to 80 mg/ml.
In our study only 20% of the patients (5 out of 25) in patients receiving levobupivacaine7.5% mg in the L2 space required intraoperative rescue analgesia but only 4% of the patients (1 out of 25) required intraoperative rescue analgesia in each of the remaining groups. Although it did not reach statically significance (P = 0.082), the success rate of levobupivacaine 7.5 mg in the L 2-3 space is only 80%. The finding is similar to that of Gautier et al.  who found that levobupivacaine 8 mg was effective in 80% compared to bupivacaine 8 mg which was effective in 97%. We have shown that 80% effectiveness can be achieved with levobupivacaine 7.5 mg given in the L 2-3 space in our study population of shorter stature. However, one drawback of our study is that we have not included patients receiving levobupivacaine or bupivacaine 7.5 mg given in the lower space (L 3-4 ). We thought that it might be unethical in the light of the previous study. 
Vasopressors for intraoperative hypotension were required evenly in 24%, 48%, 32%, and 28% of the Group I to Group IV, respectively. None of the parturients required atropine for intraoperative bradycardia. There are no significant differences in the side effects [Table 3].
| Conclusion|| |
To conclude, at a lower dose, there is no much difference between levobupivacaine and bupivacaine. At a higher dose, the duration of action bupivacaine seems to be longer. Giving the block in higher space seems to have an effect in increasing the duration of the block in case of levobupivacaine. Levobupivacaine 7.5 mg can be used in LSCS when given in L 2-3 space. The degree of motor block between levobupivacaine and bupivacaine is similar. Hemodynamic stability is more with levobupivacaine.
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| References|| |
Hawkins JL, Koonin LM, Palmer SK, Gibbs CP. Anesthesia-related deaths during obstetric delivery in the United States, 1979-1990. Anesthesiology 1997;86:277-84.
Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979;51:285-7.
Burlacu CL, Buggy DJ. Update on local anesthetics: Focus on levobupivacaine. Ther Clin Risk Manag 2008;4:381-92.
Luck JF, Fettes PD, Wildsmith JA. Spinal anaesthesia for elective surgery: A comparison of hyperbaric solutions of racemic bupivacaine, levobupivacaine, and ropivacaine. Br J Anaesth 2008;101:705-10.
Gulen G, Cakir G, Ulgey A, Faith U, Cihangir B, Isin G, et al
. A comparison of spinal anesthesia with levobupivacaine and hyperbaric bupivacaine for caesarean section: A randomized trial. Open J Anesthesiol 2012;2:84-9.
Gautier P, De Kock M, Huberty L, Demir T, Izydorczic M, Vanderick B. Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and bupivacaine for caesarean section. Br J Anaesth 2003;91:684-9.
Bremerich DH, Kuschel S, Fetsch N, Zwissler B, Byhahn C, Meininger D. Levobupivacaine for parturients undergoing elective caesarean delivery. A dose-finding investigation. Anaesthesist 2007;56:772-9.
Sanansilp V, Trivate T, Chompubai P, Visalyaputra S, Suksopee P, Permpolprasert L, Bormann BV. Clinical characteristics of spinal levobupivacaine: Hyperbaric comparedwith isobaric solution. Scientific World Journal 2012;95:544-9.
McLeod GA. Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose. Br J Anaesth 2004;92:547-51.
Mercier EJ, Benhamou D. Promising non-narcotic analgesic techniques for labour. Baillieres Clin Obstet Gynaecol 1998;12:397-407.
Bromage PR. A comparison of hydrochloride and carbondioxide salt of lidocaine and prilocaine in epidural analgesia. Acta Anaesthesiol Scand 1965;16 Suppl 1:55-69.
Charles BB, Gary R, Strichat Z. Local anesthetics. In: Miller RD, Cohen NH, Eriksson LI, Fleisher LA, Wiener-Kromish JP, Young WL, editors. Miller's Anesthesia. 8 th
ed. Philadelphia: Saunders; 2015. p. 1028-53.
Hakan Erbay R, Ermumcu O, Hanci V, Atalay H. A comparison of spinal anesthesia with low-dose hyperbaric levobupivacaine and hyperbaric bupivacaine for transurethral surgery: A randomized controlled trial. Minerva Anestesiol 2010;76:992-1001.
Pitkänen MT. Body mass and spread of spinal anesthesia with bupivacaine. Anesth Analg 1987;66:127-31.
Chridtophe D, Chrystelle S, Bernard D, Xavier C. Regional anesthesia in children. In: Miller RD, Cohen NH, Eriksson LI, Fleihser LA, Wiener-Kromish JP, Young WL, editors. Miller's Anesthesia. 8 th
ed. Philadelphia: Saunders; 2015. p. 2706-56.
Glaser C, Marhofer P, Zimpfer G, Heinz MT, Sitzwohl C, Kapral S, et al.
Levobupivacaine versus racemic bupivacaine for spinal anesthesia. Anesth Analg 2002;94:194-8.
Alley EA, Kopacz DJ, McDonald SB, Liu SS. Hyperbaric spinal levobupivacaine: A comparison to racemic bupivacaine in volunteers. Anesth Analg 2002;94:188-93.
Casati A, Moizo E, Marchetti C, Vinciguerra F. A prospective, randomized, double-blind comparison of unilateral spinal anesthesia with hyperbaric bupivacaine, ropivacaine, or levobupivacaine for inguinal herniorrhaphy. Anesth Analg 2004;99:1387-92.
Hocking G, Wildsmith JA. Intrathecal drug spread. Br J Anaesth 2004;93:568-78.
Schug SA. Correction factor for comparisons between levobupivacaine and racemic bupivacaine. Reg Anesth Pain Med 2001;26:91.
[Table 1], [Table 2], [Table 3]