European Journal of Cardiovascular Medicine

The first regional anesthetic technique that was performed was the subarachnoid block, and the first and foremost surgery was done by August Bier in 1898 in Germany. [1] The subarachnoid block is one of the most common, effective, and safe practices for a dense and rapid sensory and motor blockade with good relaxation of muscles.[2]

Levobupivacaine is an S (-) enantiomer of racemic bupivacaine and a long-acting amide-type anesthetic drug. The clinical efficiency of Levobupivacaine is similar to Bupivacaine but has a lesser detrimental action on the cardiovascular system and the nervous system. [3] It has a negative inotrope effect, less QRS interval impact, and stroke index compared to Bupivacaine. [4] It has subarachnoid blockade effects similar to Bupivacaine but a faster regression of motor blockade. At low doses, it produces differential neuraxial blockade with preserved motor function. [5]

Ropivacaine is an amide-type pure S (-) enantiomer of Bupivacaine. It gaining increased popularity due to its decreased impact on the cardiovascular system and has lower neurological incidence and is therefore used as an alternative in ambulatory surgeries instead of lidocaine. [6,7] Pka of ropivacaine is similar to bupivacaine but its solubility in fat is less and shows that its potency to block A-alpha fibers is late compared to bupivacaine. The effectiveness and spread of the given drug are not altered by the position of the patient, which is an added benefit of using this drug. Ropivacaine produces profound blockade compared to bupivacaine. [8] The benefit of using the subarachnoid block is due to its least toxic nature and its earlier recovery from the blockade. [9]

Intrathecal opioids when combined with local anesthetics – enhance the duration of sensory blockade without any increase in the sympathetic blockade. It attains an adequate grade of the subarachnoid block with a subordinate dosage of local anesthetics. [10] Buprenorphine is a long-acting, lipid-soluble drug that is a thebaine derivative. It activates the μ-opioid receptor partially and is a weak ĸ receptor antagonist and δ receptor agonist. It is used as an additive in the subarachnoid block and a remedy for acute/severe pain. Since Buprenorphine segregates from μ-opioid receptor very slowly, it results in a longer shelf-life and has lower dependence. It is a potent analgesic that acts on the central nervous system. [11]

This study was performed in the Department of Anaesthesiology, Chettinad Hospital and Research Institute, Kelambakkam, Chennai. Approval from Institutional Human Ethics Committee was obtained and Informed consent and written consent were also obtained from all participants.

Seventy patients were selected, randomized, and grouped into two with thirty-five patients each by the use of a computer-generated randomization code. Ages 18 to 65 years of both male and female, under American Society of Anaesthesiologists (ASA) Grades I and II undergoing lower abdominal and lower limb orthopedics surgeries within the period of 60 minutes were included. Patients with peripheral neuropathy, pregnant women, and patients having hypersensitivity to the drugs used in the study were excluded.

All the patients were assessed preoperatively. An IV access with an 18-gauge IV cannula was secured inside the operating theatre and Ringer’s lactate solution was connected at 10ml/kg. Hemodynamic parameters such as continuous Electrocardiogram (ECG), Heart Rate (HR), Oxygen Saturation (SpO2), and Non-invasive Blood Pressure (NIBP) were monitored throughout the procedure.

The investigator of the study was blinded to the allocation of groups and the preparation of the study drug which was done by an anaesthesiologist not involved in the assessment.

Group A: 3.5 ml of 0.5% Isobaric Inj. Levobupivacaine + 0.2 ml of Inj. Buprenorphine (60µg).

Group B: 3.5ml of 0.75% Isobaric Inj. Ropivacaine + 0.2 ml of Inj. Buprenorphine (60µg).

All patients were in an upright position, under aseptic precautions L3-L4 intervertebral space was palpated and infiltrated with 2 ml of 2% Inj. Lignocaine. Subarachnoid space was accessed in the midline with the help of 25 G Quincke’s needle. The appropriate position of the needle is confirmed by the free backflow of CSF. The study volume (3.7 ml) was injected slowly in the subarachnoid space. The patient is then made to lie down and an assessment was done for the sensory and motor blockade. The onset was assessed as the baseline, 3 min intervals of up to 15 mins and 5 mins intervals of up to 30 minutes.

The onset of Sensory blockade, assessed using Gromley and Hill 1996, was the time taken to achieve complete loss of temperature sensation at dermatome T8 (Grade 0 - Normal sensation, Grade 1 - Blunted sensation, Grade 2 - No sensation) and the sensory blockade duration was the time taken from the onset of sensory blockade to the time at which the patient sought post-operative pain analgesia (VAS ≥ 3).

The onset of motor blockade, according to the modified Bromage scale, was the time taken to achieve complete motor blockade (Grade 3) and the motor blockade duration was the time period from the onset of motor blockade to the time at which the patient can flex the knees (Grade 0).

Modified Bromage score ^[9]

Inadequacy of the subarachnoid blockade leading to conversion of the procedure to general anesthesia was excluded from the study. The time period for two-segment regression up to T10 was noted. The regression of the motor blockade up to a score of 0 for every 30 minutes was assessed using the Modified Bromage score.

Evaluation for pain was done postoperatively every 30 minutes using “Visual Analogue Score (VAS: score 0 - no pain, score 10 – most terrible pain)”. When the patient had complaints of pain and VAS ≥ 3, Inj. Paracetamol 900 mg IV was given and the study was terminated.

Visual Analogue score

Side effects such as Hypotension (20 % fall in systolic blood pressure from baseline) were treated with Inj. Ephedrine 6 mg IV, Bradycardia (heart rate less than 50 bpm) was treated with Inj. Atropine 0.6 mg IV, Nausea and vomiting with Inj. Ondansetron 4 gm IV, Shivering with Inj. Tramadol 50 mg slow IV was noted down.

STATISTICAL ANALYSIS

The sample size was calculated with the mean duration of sensory block, the power of study as 80%, and alpha error as 5% was 32 in each group as per the study by Jagtap S et al. Another 3 subjects were added to the study to account for the non-participation rate of about 10%. Thus, the final sample size was 70 which is 35 subjects in each group. An odds ratio with 95% CI was presented.

Descriptive analysis was carried out by mean and standard deviation for quantitative variables and categorical variables. Graphical representations such as bar diagrams, pie diagrams, and box plots were used to represent data. Quantitative variables such as age, gender, and weight between the two groups were compared using an independent sample t-test. Two-way repeated measures ANOVA were used to compare time-changing variables. Categorial variables such as frequency, scores and proportions were compared using the Chi-square test or Fischer exact test. The level of statistical significance was taken as P ≤ 0.05. Collection and analysis of all the data was done with SPSS statistical software.

Out of the seventy selected patients, thirty-five patients (50%) were allotted to the Levobupivacaine group - 0.5% Isobaric Inj. Levobupivacaine 3.5 ml with Inj. Buprenorphine 0.2 ml (60µg) and thirty-five patients (50%) were allotted to the Ropivacaine group - 0.75% Isobaric Inj. Ropivacaine 3.5ml with Inj. Buprenorphine 0.2 ml (60µg). The quantitative variables such as age (P value 0.445), weight (P value 0.442) or gender (P value 0.322) did not have any statistical significance among both the groups (Tables 1 and 2).

Table 1: Comparison of mean of age and weight between study groups

Table 2: Comparison of gender between study groups

The mean time taken to achieve T8 in Levobupivacaine was 7.37 ± 3.59 minutes and in Ropivacaine was 9.66 ± 3.56 minutes, and the discrepancy between the two groups was significant statistically (P value 0.009). The mean time taken to achieve T6 in Levobupivacaine was 11.71 ± 4.18 minutes and in Ropivacaine was 15.48 ± 4.12 minutes and the discrepancy between the groups was significant statistically (P value <0.001). The mean time taken for complete motor blockade in Levobupivacaine was 6.51 ± 2.36 minutes and in Ropivacaine was 8.49 ± 2.95 minutes, and the results obtained between study groups were significant statistically (P value 0.003). The mean duration of motor block in the Levobupivacaine group was 192.86 ± 49.5 minutes and in the Ropivacaine group was 163.71 ± 36.63 minutes which was significant statistically (P value 0.007). The mean time to reach VAS ≥ 3 and the need for rescue analgesia in Levobupivacaine was 168.86 ± 42.48 minutes and in Ropivacaine was 138.86 ± 30.94 minutes, found to have statistical significance (P value 0.001) (Table 3).

Table 3: Comparison of sensory and motor block characteristics between the two groups

There was no remarkable statistical variation (P value > 0.05) in heart rate, systolic blood, diastolic blood pressure, and mean arterial pressure at different follow-up periods between study groups (Fig 1-4).

*No statistical test was done - due to zero subjects in the cells

The primary objective of this study was to compare the onset of sensory blockade and motor blockade, duration of sensory blockade, two-segment regression time, hemodynamic stability, the time of requirement of analgesic and side effects between 0.5% Isobaric Levobupivacaine (3.5 ml) with Buprenorphine (0.2ml – 60 μg) and 0.75% Isobaric Ropivacaine (3.5 ml) with Buprenorphine (0.2ml – 60 μg) under subarachnoid block in patients undergoing surgeries.

The subarachnoid block generated by Levobupivacaine is identical to Bupivacaine in terms of the level of blockade and recovery.^[12] In scenarios where the commencement of motor and sensory blockade needs to be accelerated then hyperbaric levobupivacaine is used due to its rapid onset of action. ^[13] Ropivacaine produces profound blockade compared to bupivacaine. The benefit of using Ropivacaine in the subarachnoid block is due to its least toxic nature and its earlier recovery from the blockade. ^[9]

The mean onset of sensory block in the levobupivacaine group and the ropivacaine group had a P value of 0.009 which was a statistically significant value similar to a study done by Jain S et al., ^[14] which showed a P value of 0.001.

Our study showed that the mean onset of motor blockade was longer in the Ropivacaine group at 8.49 ± 2.95 minutes compared to the Levobupivacaine group which was at 6.51 ± 2.36 minutes. The contrast between the two study groups was statistically and clinically significant (P value 0.003), similar to the study conducted by Athar et al., ^[9] which showed that the time of onset of motor blockade for Group Levobupivacaine compared to Group Ropivacaine was also statistically remarkable (P value < 0.0001). A study conducted by Jindal et al., ^[15] showed that the average time for onset of motor blockade in the Levobupivacaine group compared to the Ropivacaine group showed a P value of 0.19 which was not statistically significant.

Among the two study groups, the mean regression of sensory level up to T10 in the Levobupivacaine group and in the Ropivacaine group was statistically significant (P value <0.001) in our study. Jain S et al., ^[14] in their study, showed that the mean duration of sensory block in the Levobupivacaine and Ropivacaine group showed a P value of 0.037 which was statistically significant and results were comparable to our study.

The mean time for the complete motor block in the Levobupivacaine was at 6.51 ± 2.36 minutes and in Ropivacaine was at 8.49 ± 2.95 minutes, showing remarkable significance between the study groups (P value 0.003), and the mean duration of the motor blockade between both the groups showed significance in statistics (P value 0.007). In a study conducted by Patel et al., ^[5] the mean duration of motor blockade among the Levobupivacaine group and the Ropivacaine group showed a P value < 0.001 and results were comparable to our study.

The hemodynamic parameters such as Heart rate (HR), Systolic blood pressure (SBP), Diastolic blood pressure (DBP), and Mean arterial pressure (MAP) were compared among the study groups. In the study done by Athar et al., ^[9] on Levobupivacaine or Ropivacaine Based on equipotent doses in spinal anesthesia where 3ml of 0.5% Levobupivacaine and 3ml of 0.75% Ropivacaine was given to 2 groups respectively. The study reported that efficiency, lesser adverse effects, and hemodynamics make Ropivacaine preferable for ambulatory surgeries and other surgical procedures that do not need hypotension, while Levobupivacaine can be utilized in long procedures.

All the participants in the current study were monitored with the help of a pulse oximeter and NIBP in post-operative time and there were no fluctuations in blood pressure and reduction in oxygen saturation among the study groups. The mean Visual Analogue Score among the Levobupivacaine group was at 168.86 ± 42.48 minutes and in the Ropivacaine group was at 138.86 ± 30.94 minutes which was statistically significant (P value 0.001). In a study by Malav et al., ^[16] there was a significant difference between the groups in the VAS score measured at 14 hours postoperatively 90% of group R patients achieved a VAS score of ≥ 3 compared with group L, which was 0% in 14 hours of observation. The results were comparable to my study.

The occurance of side effects among the study groups such as nausea, bradycardia, vomiting, hypotension, and shivering did not show any statistically significant difference. (P value >0.05). Similar findings were reported in a study by Athar et al., ^[9] where no incidence of Post Dural Puncture Headache or any other significant adverse effect was observed in either group. Hypotension was the most common side effect seen in both groups, however, it was significantly not different (P value > 0.05). A study by Jagtap et al., ^[10] also showed similar findings where no statistically significant difference in side effects between the study groups.

Through this study, we conclude that Levobupivacaine 0.5% with Buprenorphine 60 μg has earlier initiation of motor and sensory blockade, prolonged mean duration of motor blockade, longer two-segment regression time, and better post-operative analgesia in comparison to Ropivacaine 0.75% with Buprenorphine 60 μg without any significant differences in hemodynamic parameters and side effects.

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