European Journal of Cardiovascular Medicine

Spinal anaesthesia is the preferred anaesthetic technique for perianal surgeries owing to its simplicity, cost-effectiveness, excellent muscle relaxation, and postoperative analgesia. The ideal local anaesthetic for spinal anaesthesia in these procedures should have a rapid onset, adequate sensory and motor block, prolonged postoperative analgesia, and a favourable safety profile.[1]

Bupivacaine has long been the gold standard for spinal anaesthesia. However, its potential for serious cardiotoxicity, particularly following accidental intravascular injection, has prompted the development of newer, safer alternatives.[2] Among these, levobupivacaine (the pure S(-)-enantiomer of bupivacaine) and ropivacaine (a pure S(-)-enantiomer propyl homologue of bupivacaine) have emerged as clinically relevant options with reduced cardiotoxic potential.[3,4]

Levobupivacaine shares many of the pharmacokinetic properties of racemic bupivacaine but exhibits a more favourable cardiovascular and central nervous system toxicity profile.[5] Studies have demonstrated that intrathecal levobupivacaine produces slightly shorter sensory and motor block duration compared to racemic bupivacaine, with a comparable onset.[6] Ropivacaine, another long-acting amide local anaesthetic, is structurally similar to bupivacaine and is known to produce less motor blockade at equivalent sensory block levels, a property attributed to its differential effect on sensory versus motor nerve fibres.[7]

While both agents have been individually compared against racemic bupivacaine in various surgical settings, direct head-to-head comparisons of hyperbaric formulations of levobupivacaine and ropivacaine in the context of perianal surgery are lacking in the literature.[8,9] Perianal surgeries require reliable perineal anaesthesia without the need for high spinal block levels, making them an ideal model for evaluating subtle differences between local anaesthetic agents.

Gautier and colleagues compared isobaric intrathecal ropivacaine, levobupivacaine, and bupivacaine for Caesarean section and demonstrated that bupivacaine had a superior success rate and longer duration of analgesia and motor block than both levobupivacaine and ropivacaine.[10] However, their study used isobaric solutions and a different surgical context. The use of hyperbaric solutions and the specific demands of perianal surgery necessitate a separate investigation.

Therefore, this prospective randomised double-blind study was designed to compare the efficacy and safety of intrathecal hyperbaric levobupivacaine 0.5% (10 mg) with intrathecal hyperbaric ropivacaine 0.75% (15 mg) for spinal anaesthesia in adult patients undergoing elective perianal surgeries, with the primary aim of evaluating the onset of sensory and motor block, and duration of analgesia.

Study Design and Setting

This was a prospective, randomised, double-blind, parallel-group controlled trial conducted in the operation theatre complex of Sri Devaraj Urs Medical College (SDUMC) over a period of six months following Institutional Ethics Committee approval. The study was registered with the Clinical Trials Registry – India (CTRI). Written informed consent was obtained from all participants prior to enrolment.

Study Population

Adult patients of either sex aged 18–60 years, with a body mass index (BMI) < 30 kg/m², belonging to American Society of Anesthesiologists (ASA) physical status class I and II, scheduled for elective perianal surgeries were included.

Exclusion criteria: Patients with contraindications to spinal anaesthesia (coagulopathy, local infection at the injection site, raised intracranial pressure, patient refusal), morbid obesity (BMI ≥ 30 kg/m²), known hypersensitivity to amide local anaesthetics, significant cardiovascular, hepatic, or renal disease, and pregnant patients were excluded.

Sample Size

Based on a prior study by Selvin (2019), the mean (SD) time for onset of motor block was 13.4 ± 1.2 minutes in the levobupivacaine group and 12.5 ± 1.5 minutes in the ropivacaine group.11 Assuming a type I error (α) of 5% (two-tailed), power (1-β) of 80%, and using the formula:

n = (Z α/2 + Z β)² × (σ₁² + σ₂²) / (μ₁ – μ₂)²

The required sample size was calculated to be 36 subjects per group. Accounting for a 10% dropout rate, 40 patients per group were enrolled, giving a total of 80 patients. Of these, 72 patients (36 per group) completed the study per protocol.

Randomisation and Blinding

Patients were randomised into two equal groups using a computer-generated sequence of random numbers with sealed envelope allocation concealment. The study drugs were prepared by an anaesthesiologist not involved in subsequent patient assessments or data collection. Both the patient and the outcome assessor were blinded to the group allocation.

Groups

•              Group L (n = 36): Received intrathecal 2.0 ml of 0.5% hyperbaric levobupivacaine (10 mg)

•              Group R (n = 36): Received intrathecal 2.0 ml of 0.75% hyperbaric ropivacaine (15 mg)

 Anaesthetic Procedure

All patients were assessed preoperatively and fasted as per standard guidelines. On arrival in the operating theatre, standard ASA monitoring (electrocardiogram, non-invasive blood pressure, pulse oximetry) was established and baseline readings were recorded. All patients received intravenous (IV) preloading with Ringer's lactate solution at 15 ml/kg over 15 minutes prior to spinal block.

Under aseptic precautions, spinal anaesthesia was performed at the L3–L4 intervertebral space in the sitting position using a 25G Quincke spinal needle via the midline approach. After confirming free flow of cerebrospinal fluid, the study drug was administered over 30 seconds by an anaesthesiologist blinded to the drug identity. Patients were immediately turned to the supine position following injection. Lithotomy positioning was adopted for all perianal surgical procedures.

IV ephedrine 6 mg was administered as bolus doses for hypotension, defined as a fall in systolic blood pressure (SBP) to less than 90 mmHg or more than 30% below baseline. Bradycardia (heart rate < 50 bpm) was treated with IV atropine 0.6 mg.

Outcome Measures

All assessments were performed by a blinded anaesthesiologist at predetermined time points.

Primary outcomes:

1.             Onset of sensory block: Time from intrathecal injection to loss of pinprick sensation at the T12 dermatome, assessed using a 25G needle along the midclavicular line bilaterally every 2 minutes.

2.             Onset of motor block: Time from intrathecal injection to achievement of Bromage scale grade 2 (ability to move feet only, unable to flex knees).

3.             Duration of analgesia: Time from intrathecal injection to the first request for rescue analgesic (IV paracetamol 1g or diclofenac 75 mg IM).

Secondary outcomes:

•              Maximum cephalad level of sensory block

•              Duration of motor block (time from maximum motor block to Bromage grade 5 or 6)

•              Two-segment regression time

•              Haemodynamic parameters (heart rate and blood pressure) recorded at baseline, and at 2, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes

•              Intraoperative pain (VAS ≥ 4 requiring supplemental analgesia)

•              Adverse effects: hypotension, bradycardia, nausea, vomiting, pruritus, transient neurological symptoms

Motor block was assessed using the modified Bromage scale (1 = complete block; 2 = nearly complete – can move feet only; 3 = partial – can flex knees; 4 = detectable hip flexion weakness; 5 = no detectable weakness, leg raised > 10 s; 6 = no weakness, partial knee bend possible).

Statistical Analysis

Data were entered in Microsoft Excel and analysed using SPSS version 20.0 (IBM Corp., Armonk, NY). Continuous variables normally distributed were expressed as mean (SD) and compared using the unpaired Student's t-test. Non-normally distributed continuous data were expressed as median (IQR) and compared using the Mann–Whitney U test. Ordinal variables (VAS scores, Bromage scale) were analysed using the Mann–Whitney U test. Categorical variables were compared using the chi-square test or Fisher's exact test as appropriate. A p-value < 0.05 was considered statistically significant.

A total of 80 patients were enrolled; 8 patients were excluded (4 per group: 3 due to failed spinal block, 5 due to conversion to general anaesthesia or incomplete data). Seventy-two patients (36 per group) completed the study and were included in the final analysis. The two groups were comparable in demographic characteristics and baseline vitals (Table 1).

Table 1: Patient Demographic Characteristics and Baseline Parameters (Mean ± SD)

No statistically significant differences between the groups

Sensory Block Characteristics

The onset of sensory block (T12) was significantly faster in Group L compared to Group R. Similarly, the maximum cephalad level of sensory block and the two-segment regression time were comparable, but the time to regression to T12 was significantly longer in Group R. Detailed sensory block characteristics are presented in Table 2.

Table 2: Sensory Block Characteristics (Mean ± SD)

**p < 0.05 considered statistically significant; significant.

Motor Block Characteristics

Onset of motor block was significantly earlier in Group L. However, duration of motor block was significantly longer in Group R (Table 3).

Table 3: Motor Block Characteristics (Mean ± SD)

**p < 0.05 considered statistically significant; significant

Haemodynamic Parameters

Heart rate and systolic blood pressure were comparable between the groups at all time points (Table 4). There were no statistically significant differences in haemodynamic parameters at any recorded time interval.

Table 4: Haemodynamic Parameters Over Time (Mean ± SD)

No statistically significant differences between groups at any time point

Adverse Effects

The incidence of adverse effects was low and comparable between groups (Table 5). No patient in either group developed transient neurological symptoms (TNS) at postoperative follow-up on days 1 and 3.

Table 5: Adverse Effects

No statistically significant differences between groups

Surgical Anaesthesia Adequacy

All patients in both groups achieved adequate anaesthesia for the procedure without requiring intraoperative supplemental analgesia (VAS < 4 throughout). The quality of surgical anaesthesia rated by the operating surgeon was excellent or good in 94.4% of patients in Group L and 91.7% in Group R (p = 0.646).

This prospective randomised double-blind study directly compared intrathecal hyperbaric levobupivacaine 0.5% (10 mg) with hyperbaric ropivacaine 0.75% (15 mg) for spinal anaesthesia in perianal surgeries. Both agents provided clinically effective and haemodynamically stable spinal anaesthesia; however, each demonstrated distinct pharmacodynamic characteristics. Group L exhibited significantly faster onset of both sensory and motor block, while Group R offered a significantly longer duration of sensory block and postoperative analgesia.

The faster onset of sensory block observed with levobupivacaine (3.8 ± 0.9 min vs. 5.1 ± 1.2 min for ropivacaine, p < 0.001) is consistent with published literature comparing these agents. Levobupivacaine shares the same piperidine ring structure as racemic bupivacaine and exhibits comparable lipid solubility and protein binding, accounting for its more rapid neural penetration compared to ropivacaine, which has a propyl rather than butyl substitution.[3,12] Malinovsky and colleagues previously noted slower onset kinetics with ropivacaine compared to bupivacaine in intrathecal anaesthesia, attributable to differences in intrinsic anaesthetic potency and pKa.[13] Similarly, Gautier et al. observed that time to maximum cephalad spread was slightly longer in the ropivacaine group compared to bupivacaine.[10] Our findings with the direct head-to-head comparison corroborate these observations.

The onset of motor block (5.2 ± 1.1 min vs. 6.8 ± 1.4 min, p < 0.001) followed a similar pattern, with Group L achieving Bromage grade 2 earlier. This parallels the observation by Khaw et al. who noted a dose-dependent increase in the proportion of patients achieving complete motor block with ropivacaine, suggesting that at comparable equianalgesic doses, ropivacaine has a slightly inferior motor-blocking potency.[14]

A key distinguishing finding was the significantly longer duration of analgesia in Group R (148.6 ± 18.3 min vs. 128.4 ± 15.7 min in Group L, p < 0.001). This advantage of ropivacaine is consistent with previous comparative studies and may be explained by the higher milligram dose administered in the ropivacaine group (15 mg vs. 10 mg).[9,10] Ropivacaine, despite being less potent than levobupivacaine on a milligram-per-milligram basis, requires a higher dose to achieve equivalent block levels, and this larger dose mass may contribute to the prolonged analgesic effect.[7] Gautier et al. similarly documented a shorter duration of analgesia with levobupivacaine compared to bupivacaine, and attributed the finding to the lower intrinsic potency of the pure S(-)-enantiomer when used at equipotent doses.[10] Our results extend this observation to a direct comparison between the two newer agents.

The duration of motor block was also significantly longer in Group R (136.2 ± 19.8 min vs. 118.6 ± 16.4 min, p < 0.001). While a shorter duration of motor block is generally favourable for early ambulation, particularly in day-case perianal surgeries, the difference of approximately 17 minutes may have limited clinical significance for inpatient procedures. Notably, the ropivacaine group's longer motor block duration is paradoxical given ropivacaine's widely cited property of producing less motor block than bupivacaine at equivalent sensory block levels.[4,7] This is most likely explained by the dose difference – 15 mg of ropivacaine was needed to achieve comparable block quality to 10 mg of levobupivacaine, confirming the well-established potency hierarchy in which levobupivacaine is more potent than ropivacaine on a milligram basis.[8,10]

Both agents demonstrated comparable haemodynamic stability throughout the study period. The incidence of hypotension (Group L: 11.1%; Group R: 8.3%) and bradycardia (both groups: 5.6%) was similar (p > 0.05), consistent with the limited sympathectomy expected with the low cephalad spread (T10 level) typical in perianal surgery. These findings are in agreement with prior studies reporting favourable cardiovascular profiles of both levobupivacaine and ropivacaine.[5,12] The low and comparable incidence of nausea, vomiting, and pruritus in both groups further supports the safety of both agents.

Importantly, no patient in either group developed transient neurological symptoms on postoperative days 1 or 3, consistent with the established safety profiles of both agents. The absence of TNS is clinically significant given historical concerns with lidocaine for spinal anaesthesia in the lithotomy position, which perianal surgeries necessitate.[15]

Perianal surgery represents a unique clinical context in which spinal anaesthesia needs to be reliable but limited in cephalad spread. Both hyperbaric formulations provided adequate surgical anaesthesia without intraoperative supplementation in all cases. The surgeon-rated quality of anaesthesia was excellent or good in over 91% of patients in both groups, with no statistically significant difference.

A limitation of this study is the different milligram doses used for the two drugs (10 mg vs. 15 mg), which reflects the potency difference between levobupivacaine and ropivacaine rather than an equipotent comparison. This was intentional and clinically relevant, as the doses selected represent the lowest effective doses established in prior dose-finding studies for each drug in spinal anaesthesia.[11,14] Future studies using equipotent or equivolume designs could further refine the understanding of relative potency. The single-centre design and a sample size powered for motor block onset rather than duration of analgesia are additional limitations. Larger multicentre trials are warranted to confirm these findings.

Both intrathecal hyperbaric levobupivacaine 0.5% (10 mg) and hyperbaric ropivacaine 0.75% (15 mg) are safe and effective agents for spinal anaesthesia in perianal surgeries. Hyperbaric levobupivacaine provides a significantly faster onset of sensory and motor block, while hyperbaric ropivacaine offers a significantly longer duration of postoperative analgesia and motor block, with comparable haemodynamic stability and adverse effect profiles. The choice between the two agents may be guided by clinical context: levobupivacaine when rapid surgical readiness is desired, and ropivacaine when prolonged postoperative analgesia is the priority.

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