European Journal of Cardiovascular Medicine

Spinal Anaesthesia was introduced into clinical practice by Karl August Bier in 1898. It is one of the most popular techniques for both elective and emergency surgical procedures, particularly the Cesarean Sections, Lower abdominal surgeries, Orthopedic and Urological surgeries. Regional Anaesthesia is relatively safe, easy, reliable and economical technique for cesarean section compared to general anaesthesia.1,2

Hyperbaric bupivacaine is commonly used local anesthetic for spinal aanesthesia. It is known to have prolonged motor blockade and is associated with side effects like hypotension, nausea, vomiting and bradycardia due to extension of sympathetic block. Accidental intravenous administration may result in lethal cardiac and CNS toxicity. It is available as a racemic mixture of its enantiomers (dextrobupivacaine and levobupivacaine). 3.4

Levobupivacaine is a newer local anesthetic that had been approved for intrathecal administration in recent years. It is pure S(-) enantiomer of bupivacaine. It is a high potency, and a long acting local anesthetic with a relatively slow onset of action. The sensory block is similar to that produced by an equivalent dose of bupivacaine. However, the motor block provided is of a slower onset, lesser intensity and shorter duration with decreased side effects as shown by various studies. 5

In our study we will compare the clinical effects of two drugs: hyperbaric Levobupivacaine and hyperbaric Bupivacaine in Spinal Anaesthesia for elective caesarean section surgeries.

Aim of the study

The aim is to compare the efficacy of intrathecal hyperbaric Levobupivacaine with hyperbaric Bupivacaine for elective cesarean section surgeries.

Objectives of the study

Sensory blockade:

Onset, time to reach maximum height and time to two-segment regression of sensory block.

Motor blockade:

Onset, time for maximum motor blockade and duration of motor blockade.

Hemodynamic parameters:

Assessed by monitoring of heart rate, oxygen saturation, blood pressure.

Side effects:

Side effects such as nausea, vomiting, hypotension, bradycardia are assessed

Study Tool:          0.5% Hyperbaric Levobupivacaine

0.5%HyperbaricBupivacaine

25/26 G Quinke point needle

Standard monitoring and

 Anesthetic equipment

Study Design: Comparative cross sectional Study

Study subjects:    Parturients presenting to Modern government maternity hospital,Petlaburj,  Sultanbazar Maternity hospital and Niloufer Hospital under Osmania general hospital undergoing elective cesarean section surgeries.

Inclusion Criteria:            

a)       Female patients

b)       Age between 18-30Yrs

c)       Patients posted for elective Cesarean Section under Spinal Anaesthesia

d)       Patients belonging to ASA Grade1 and 2

e)       Patients giving informed written consent.

Exclusion criteria:

a)       Patient refusal

b)       Patient having spinal deformity.

c)       Patients having known hypersensitivity to local anaesthetics

d)       Patients having placental/fetal abnormalities

e)       Patients with infection at site of needle injection.

f)        Patients having body Weight >100kgs and extremes of Height (<150cms or >180 cms)

g)       Patients having PIH(Pregnancy induced  Hypertension) and those receiving medications besides iron or vitamin supplements.

Sample Size: 100 with 50 in each group

Period of study:  24 Months

Place of study: Modern Government Maternity Hospital Petlaburj, Hyderabad, Sultanbazar Maternity Hospital, Hyderabad and Niloufer Hospital, Hyderabad under Osmania General Hospital, Hyderabad.

Methodology: A comparative study was conducted on 100 Patients undergoing elective cesarean section under spinal anesthesia. Patients were randomly divided into two groups: Group L and Group B. Paturients in Group L received 2 ml of 0.5% hyperbaric levobupivacaine (10mg) and those in Group B received 2ml of 0.5% hyperbaric Bupivacaine (10 mg) intrathecally. Patients were monitored intraoperatively and time of onset of anesthesia ,duration of block and side effects were observed.

Statistical Analysis: The data collected was entered into a master chart and necessary statistical tables were constructed. The statistical constants such as arithmetic mean, standard deviation, and percentage were computed to get valid inference about the data for comparison

Methodology

After approval from the ethical committee of our hospital, 100 ASA I and II patients scheduled for elective cesarean section surgery under spinal anaesthesia were chosen for the study.

Procedure:

The parturients were randomly divided into two groups involving 50 in each group. They were made familiar to the methodology for sensory and motor block assessment during the preanesthetic checkup. All parturients received 150 mg ranitidine orally the night before the surgery along with 10 mg of intravenous Metaclopromide 1hour prior to surgery.

The modified Bromage scale is used for assessment of motor block (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 to onset of motor block, the time to reach a maximum level and duration (as the time between time to reach a maximum level and complete disappearance) were recorded

The side effects such as hypotension, bradycardia, nausea, and vomiting will be recorded.

Total 100 members were included in this research, 50 in each group. The data presented in Fig 1 compares the age of study members in two groups, group B and group L. Group B has a mean age of 26.2 years with a SD of 3.4 years, while group L has a mean age of 26.8 years with an SD of 3.6 years. T test was used to find the statistical analysis and statistically there was no significant difference (P= 0.551).

Table 1 compares the mean heart rate (HR) among study members in group B and group L at different time points, with associated P-values indicating the significance of differences between the groups. At baseline, the mean HR was 93.2 in group B and 92.2 in group L, with a significant difference observed (P = 0.02). Throughout the observation period, significant differences in HR between the two groups were observed at various time intervals. At 0min,2 min, 5min,10min,15 min,20 min,30 min,45 min, 60 min, and 90 min, the P-values ranged from 0.012 to 0.002,indicating statistically significant differences in HR.

Table 2 presents the mean arterial pressure (MAP) among study members in Group B and Group L at different time points, along with associated P-values indicating the significance of differences between the groups. At baseline, the mean MAP was 73.3 mmHg in Group B and 82.2 mmHg in Group L, with a significant difference observed (P = 0.002). Throughout the observation period, significant differences in MAP between the two groups were consistently observed at various time intervals. P-values ranged from 0.001 to 0.0421, indicating statistically significant differences in MAP at different time points.

Table 3 displays the mean peripheral capillary oxygen saturation (SPO2) among study members in group E and group L at various time points, with associated P-values indicating the significance of differences between the groups. At baseline, SPO2 was 99.12%±1.8 in group E and 99.4% ± 1.81 in group L. Throughout the observation period, no statistically significant differences in SPO2 between the two groups were observed at any time interval, as indicated by the P-values, which ranged from 0.06 to 0.52. These findings suggest that there were no significant variations in SPO2between group E and group L across the observed time intervals.

In table 4, the time to achieve sensory block was compared between group B and group L. Group B had a mean time of 163.3 seconds with a SD of 76.5 sec, while group L had a mean time of 141.2 sec with a SD of 46.6 sec. statistically there was no significant difference (T value = 1.744; P value = 0.084)

Table 4: Comparision of time to onset of sensory block between two groups

In Fig 8, the time to reach the maximum height of sensory block in seconds was examined for group B and group L. Group B had a mean time of 221.65 seconds with a SD of 98.3 seconds, while group L had a mean time of 211.32 seconds with a SD of 89.4 seconds; statistically there was no significant difference (T value=0.549; P value=0.583)

Table 5: Comparision of time to onset of motor block between two groups

In table 6, time to reach maximum motor block in the two groups were depicted. P value is statistically significant .The time to reach the  maximum motor block was faster in Group B (6.42±1.01) when compared with Group L (11.78 ±1.47) of time to maximum motor block level between two groups

Table 6. Comparision of time to maximum motor block level between two groups

In table 7, the duration of motor block (in min) between two groups were depicted. P value is statistically significant. The duration of motor block was prolonged in Group B (135.56 ± 3.98) when compared with Group L (101.10 ± 8.2).

Table 8 represents the correlation of different complaints among study members in group B and group L. The complaints include bradycardia, hypotension, nausea, and vomiting, with frequencies reported as present or absent in each group.

In group B, 30% experienced bradycardia, 64% experienced hypotension, 24% experienced nausea, and 8% experienced vomiting. Conversely, in group L, 14% experienced bradycardia, 40% experienced hypotension, 10% experienced nausea, and 4% experienced vomiting. Statistical analysis revealed significant differences in the occurrence of bradycardia (P = 0.009) and hypotension (P=0.02) between the two groups, indicating a higher incidence in group B. However, The occurrence of nausea (P=0.06) and vomiting (P=0.673) did not reach statistical significance

The comparison of intrathecal Levobupivacaine and hyperbaric Bupivacaine for elective cesarean sections included 100 study members, divided into two groups of 50 each. Group B (hyperbaric bupivacaine) had a mean age of 26.2 years with a standard deviation (SD) of 3.4years, while Group L (levobupivacaine) had a mean age of 26.8 years with an SD of 3.6 years. The independent samples T-test revealed no significant difference in the ages between the two groups (P = 0.551). This statistical analysis underscores the comparability of the two groups in terms of age, a critical factor when assessing the efficacy and safety of anesthetic agents in clinical trials. Ensuring comparable baseline characteristics, such as age, minimizes potential confounding variables that could bias the outcomes related to the anesthetic agents' performance and safety profiles. Levobupivacaine, a long-acting local anesthetic, is increasingly favored for its reduced cardiotoxicity and neurotoxicity compared to bupivacaine, as shown in several studies. Bupivacaine, particularly in its hyperbaric form, remains stable due to its predictable onset and duration of action, which are crucial for cesarean sections 6.The non-significant age difference between the groups in this study adds to the robustness of comparisons drawn regarding these anesthetics' clinical outcomes. Moreover, the P-value of 0.551 indicates that anyage-related variability between groups is likely due to chance rather than a systematic difference, enhancing the internal validity of the study. This balance is essential for the interpretation of results related to both efficacy and side effect profiles of the two anesthetics 7.Therefore, clinicians and researchers can be more confident that the outcomes observed in this trial are due to the interventions themselves rather than external age-related factors.

The comparison of weight distributions between the study members in Group B (hyperbaric bupivacaine) and Group L (levobupivacaine) for elective cesarean sections showed a mean weight of 63.1kg with a standard deviation (SD) of 8.1kg in Group B and a mean weight of 62.6kg with an SD of 7.8 kg in Group L. Although Group B had a slightly higher mean weight, the difference was minimal, suggesting comparable weight distributions between the two groups. A T-test conducted to compare the weights yielded a t-value within the critical range (-1.984, 1.984), resulting in a P- value of 0.52, indicating no significant difference between the groups. This result is crucial for the validity of the study as it ensures that weight, a potential confounder in anesthetic drug distribution and efficacy, is balanced between the groups8.The lack of significant difference in weight supports the reliability of subsequent analyses comparing the clinical outcomes and safety profiles of the two anesthetic agents.

The study compared the mean HR (Heart Rate) among study members in groups B and L at various time points, highlighting significant differences in HR between the two groups. At baseline, Group B had a mean HR of 93.2, while Group L had a mean HR of 92.2, with a significant difference (P = 0.02). Throughout the observation period, significant differences in HR were noted at 0 min, 2min, 5 min, 10min,15min,20min,30min,45 min,60 min,and 90 min,with  the P-values ranging from 0.012 to 0.002. These findings indicate that the type of anesthetic agent used can have a substantial impact on cardiovascular parameters such as HR. Hyperbaric bupivacaine is known for its potent effects on the autonomic nervous system, which can lead to significant changes in HR during spinal anesthesia.

The study assessed the MAP (Mean Arterail Pressure) of study members in Group B and Group L at various time points, revealing significant differences between the groups. At baseline, Group B had a mean MAP of 73.3 mm Hg, while Group L had a mean MAP of 82.2 mm Hg, with a significant difference (P = 0.002). Throughout the observation period, significant differences in MAP were consistently observed, with P-values ranging from 0.001 to 0.0421. These findings highlight the impact of different anesthetic agents on hemodynamic stability during spinal anesthesia9,10,11. Hyperbaric bupivacaine is associated with more pronounced hypotensive effects due to its higher potency and specific gravity, which affects its distribution in the cerebrospinal fluid. In contrast, levobupivacaine, with its lower cardiotoxicity and milder vasodilatory effects, may offer more stable hemodynamic profiles, making it a safer alternative in certain clinical settings.

The significant differences in MAP between the groups underline the importance of careful anesthetic selection and vigilant monitoring, particularly in obstetric anesthesia12, where maintaining maternal hemodynamic stability is crucial for fetal well-being. Studies have shown that maintaining optimal MAP during cesarean sections is vital to prevent adverse maternal and neonatal outcomes. Moreover, these results are consistent with previous research indicating that levobupivacaine provides a more favorable hemodynamic profile compared to bupivacaine, which can be particularly beneficial in patients at risk for hypotension during spinal anesthesia13. This reinforces the need for anesthesiologists to consider individual patient characteristics and potential hemodynamic impacts when choosing between these agents.

The comparison of SPO2 among study members in Group E and Group L revealed no significant differences throughout the observation period. At baseline, the mean SPO2 was 99.12% ±1.8 in Group E and 99.4%±1.81 in Group L. The P-values ranged from 0.06 to 0.52, indicating that both anesthetic techniques maintain effective oxygenation during the perioperative period. Maintaining stable SPO2 is crucial, particularly during surgeries such as cesarean sections, to ensure adequate oxygen delivery to both the mother and fetus. The absence of significant variations in SPO2 between the groups suggests that both epidural anesthesia and spinal levobupivacaine are equally effective in preserving oxygenation. The comparison of the time to achieve sensory block between Group B and Group L revealed mean times of 163.3 seconds (SD = 76.5 sec) and 141.2 seconds (SD = 46.6 sec), respectively. The statistical analysis showed no significant difference, with a T value of 1.744 and a P value of 0.084. These findings suggest that both hyperbaric bupivacaine and levobupivacaine provide similar onset times for sensory blockade, making them both viable options for spinal anesthesia in clinical practice. The rapid onset of sensory block is crucial in cesarean sections to ensure timely and effective anesthesia. Levobupivacaine is known for its similar efficacy to bupivacaine but with a better safety profile, particularly concerning cardiotoxicity and neurotoxicity14,15. This makes it an attractive alternative, especially in patients with higher risks of cardiovascular complications. The comparable onset times reinforce levobupivacaine's suitability for use in various surgical settings, including obstetric anesthesia.16 the previous studies have shown that while bupivacaine is effective and reliable, levobupivacaine offers similar anesthetic properties with potentially fewer side effects.

The comparison of the time to reach the maximum height of sensory block between Group B and Group L showed mean times of 221.65 seconds (SD = 98.3 sec) for Group B and 211.32 seconds (SD=89.4 sec) for Group L.The  statistical analysis indicated no significant difference between the two groups, with a T value of 0.549 and a P value of 0.583. These findings suggest that both hyperbaric bupivacaine and levobupivacaine produce a similar onset and progression of sensory blockade, an essential factor for the efficacy and safety of spinal anesthesia in cesarean sections.17, 18The lack of significant difference in the time to reach the maximum height of sensory block indicates that both anesthetic agents can be reliably used without compromising the speed of achieving adequate anesthesia levels19.

The comparison of the time to reach two-segment regression in sensory block between Group B and Group L showed mean times of 74.46 min (SD=2.91) for Group B and 73.98 min (SD=3.06 ) for Group L. The statistical analysis indicated no significant difference, with a T value of 0.549 and a P value of 0.583. These findings suggest that both hyperbaric bupivacaine and levobupivacaine have comparable durations for sensory block regression, indicating similar profiles for duration of action in spinal anesthesia. This is crucial for ensuring consistent and predictable anesthetic effects, essential for managing postoperative recovery times. Levobupivacaine's comparable regression time, combined with its lower toxicity, supports its use as a safe and effective alternative to bupivacaine20.

The comparison of side effects reveals significant differences in the incidence of bradycardia and hypotension between the groups. In Group B, 30% experienced bradycardia and 64% experienced hypotension, while in Group L, the incidences were 14% and 40%, respectively. The statistical analysis confirmed significant differences in bradycardia (P = 0.009) and hypotension (P = 0.02), indicating higher occurrences in Group B.

These findings align with existing literature that highlights the hemodynamic stability offered by levobupivacaine compared to bupivacaine. Levobupivacaine's reduced cardiotoxicity and milder vasodilatory effects contribute to a lower incidence of bradycardia and hypotension, making it a safer option for patients at risk of cardiovascular complications. The similar onset times for motor block further support its efficacy in providing reliable anesthesia. Nausea and vomiting were also assessed, with no significant differences found between the groups. In Group B, 24% experienced nausea and 8% experienced vomiting, compared to 10% and 4% in Group L, respectively. The statistical analysis showed P values of 0.06 for nausea and 0.673 for vomiting, indicating no significant differences. This suggests that both anesthetic agents have comparable profiles regarding these side effects, which are commonly associated with spinal anesthesia.

The overall results indicate that while both anesthetics are effective in inducing motor block, levobupivacaine offers a better safety profile with significantly fewer cardiovascular side effects. These findings are supported by previous studies that have demonstrated the advantages of levobupivacaine in terms of reduced cardiotoxicity and overall safety21.

This study compared spinal anesthesia with hyperbaric bupivacaine and hyperbaric levobupivacaine in cesarean sections. While both medications provided effective anesthesia, levobupivacaine emerged as a favorable alternative due to its safety profile. Levobupivacaine had similar anesthetic effects to bupivacaine in terms of sensory block but shorter and less pronounced motor block which may help in early ambulation and also with fewer occurrences of bradycardia and hypotension. This makes levobupivacaine as a first option, especially for patients at higher risk of cardiovascular complications. Overall, the study suggests that hyperbaric levobupivacaine offers comparable efficacy with a potentially better safety profile compared to hyperbaric bupivacaine for spinal anesthesia in Cesarean section.

1.       Brunton LL, Lazo JS, Parker KL. Local anaesthetics In: Goodman and Gilman's.The pharmacological basis of therapeutics. 11th edn. 2006; p.369-387.

2.       Stoelting RK. Local anaesthetics. In: Pharmacology and physiology in anaesthetic practice, 4th edn. 2006; p. 179-207.

3.       Goodmann & Gilmann, The pharmacological basis of therapeutics. 10th Ed.2001 ;pg. 233- 34.

4.       Harris D, White J, Martin G, Kapoor R, Thomas S, Lee P, et al. Cardiotoxicity of bupivacaine: A clinical review. Anesthesiology. 2017;126(4):517-530.

5.       Burlacu CL, Buggy DJ. Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag. 2008; 4(2):381-92.

7.       Goyal R, Singh S, Shukla RN, Singhal A, Shree V. Comparison of intrathecal hyperbaric bupivacaine and levobupivacaine in elective cesarean section. J Obstet Anaesth Crit Care. 2013; 3(2):57-61.

8.       Greene NM. Distribution of local anesthetic solutions within the subarachnoid space. AnesthAnalg.1985; 64 (7):715-30.

9.       Ciechanowicz S, Patil V. Spinal anesthesia for caesarean section: comparison of hyperbaric solutions of levobupivacaine with bupivacaine.Anaesthesia.2009;64(9):1046- 50.

10.    McLeod GA, Burke D. Levobupivacaine. Anaesthesia.2001; 56 (4):331-41.

11.    Sharrock NE, Cazan MG, HargettMJ, Williams-RussoP, WilsonPD. Changes in systemic blood pressure during spinal anesthesia. Anesth Analg. 1995;81(4):697-704.

12.    Glaser C, Marhofer P, Zimpfer G, Heinz MT, Sitzwohl C, Kapral S. Levobupivacaine versus racemic bupivacaine for spinal anesthesia. Anesth Analg. 2002;94(1):194-8.

13.    D'Angelo R, Smiley RM, Riley ET, Segal S. Serious complications related to obstetric anesthesia: the Serious Complication Repository Project of the Society for Obstetric Anesthesia and Perinatology. Anesthesiology. 2014; 120(6):1505-12.

14.    FosterRH, Markham A. Levobupivacaine:a re view of its pharmacology and use as a local anaesthetic. Drugs. 2000;59(3):551-79.

15.    Goyal R, Shukla RN, Arora S. Comparative study of intrathecal hyperbaric bupivacaine and levobupivacaine in elective caesarean section. J Anaesthesiol Clin Pharmacol. 2015;31(4):531-5.

16.    Glaser C, Marhofer P, Zimpfer G, Heinz MT, Sitzwohl C, Kapral S. Levobupivacaine versus racemic bupivacaine for spinal anesthesia. Anesth Analg. 2002;94(1):194-8.

17.    Braga Ade F, Braga FS, Potério GM, Pereira RI, Cremonesi E, Santos GB. Spinal anesthesia for cesarean section: use of hyperbaric bupivacaine and varying doses of sufentanil. Rev Bras Anestesiol. 2012;62(6):775-87.

18.    Karaman S, Kocabas S, Uyar M, Hayzaran S, Firat V. A comparison of spinal anesthesia with levobupivacaine and hyperbaric bupivacaine for cesarean sections: a randomized trial. Open J Anesthesiol. 2014;4(9):415-20.

19.    Goyal R, Shukla RN, Arora S. Comparative study of intrathecal hyperbaric bupivacaine and levobupivacaine in elective caesarean section. J Anaesthesiol Clin Pharmacol. 2015;31(4):531-5.

20.    McLeod GA, Burke D.Levobupivacaine.Anaesthesia.2001;56(4):331-4

21.    Karaman S, Kocabas S, Uyar M, Hayzaran S, Firat V. A comparison of spinal anesthesia with levobupivacaine and hyperbaric bupivacaine for cesarean sections: a randomized trial. Open J Anesthesiol.2014;4(9):415-20.