Materials and methods

Study design and ethical approval

This study was planned as a prospective, randomized, double-blind study. Ninety patients were recruited into this trial after approval by the Institutional Review Board, Sri Venkateshwaraa Medical College Hospital and Research Centre (approval SVMCH/IEC/2019-Nov/21). The study was also registered prospectively with the Clinical Trials Registry- India (CTRI) (CTRI registration no. CTRI/2020/02/023473).

Study setting and participants

We included patients with American Society of Anesthesiologists (ASA) physical status I or II, aged 18-60 years, of either sex, who were scheduled for elective surgeries involving the infraumbilical region under spinal anesthesia at Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry, India, between February 2020 and July 2021. Patients with contraindications to spinal anesthesia, including coagulopathies, infection at the injection site, patient refusal, mental illness, pregnancy, or allergy to local anesthetics, were excluded.

Randomization and blinding

Participants were randomized to receive either ropivacaine (Group R) or levobupivacaine (Group L) using a computer-generated block randomization sequence, and allocation was performed using a serially numbered, opaque, sealed-envelope approach. The subarachnoid block was performed by an experienced anesthesiologist who was not involved in the subsequent study procedures or data collection. Both the patients and the anesthesiologist responsible for data collection were blinded to group allocation. Subjects in Group R received 3 mL of 0.75% ropivacaine (7.5 mg/mL; 22.5 mg of ROPIN® 0.75%, Neon Laboratories Ltd., Mumbai, India), whereas those in Group L received 3 mL of 0.5% levobupivacaine (15 mg of LEVO-ANAWIN® 0.5%, Neon Laboratories Ltd.).

Anesthetic procedure and perioperative management

On the night before surgery, all participants received a tablet of metoclopramide 10 mg and a tablet of alprazolam 0.25 mg. On the day of surgery, a large-bore IV cannula was inserted for all patients, and baseline vital signs (blood pressure, pulse rate, SpO₂, ECG, and temperature) were recorded. Patients received coloading with Ringer’s lactate solution during administration of the subarachnoid block. Replacement fluids were administered according to body weight and intraoperative fluid losses. After randomization, the principal investigator provided the sealed envelope to the anesthesiologist responsible for administering spinal anesthesia and providing standard medical care.

The primary investigator evaluated all study parameters for each patient. Spinal anesthesia was performed using a 27-G Quincke-type spinal needle at the L3-L4 or L4-L5 intervertebral space under aseptic precautions. After confirmation of free cerebrospinal fluid flow through the spinal needle, the study drug was administered, and patients were immediately placed in the supine position. Completion of the injection was designated as “zero time” for induction of anesthesia. The onset of sensory block was assessed using a pinprick test or spirit swab every one minute until the T6 dermatomal level was achieved, and surgery was initiated after an adequate level of block was confirmed. Failure was defined as failure to achieve the T10 sensory level within 30 minutes. These patients received general anesthesia. Such cases were excluded from the analysis, and only the total number of failures was reported in the per-protocol analysis. The onset of motor block was assessed using the Modified Bromage Scale [7]. Failure to achieve Grade 3 motor block within 30 minutes was considered a failed block, and these patients were excluded from the study.

Vital signs, including pulse rate, systolic and diastolic blood pressure, mean arterial pressure (MAP), respiratory rate, and oxygen saturation (SpO₂), were monitored for 24 hours following induction of spinal anesthesia at regular intervals during the intraoperative and postoperative periods. Hypotension, defined as a MAP <60 mmHg or a reduction of >20% from baseline blood pressure, was treated with IV mephentermine 6 mg and an additional 100 mL fluid bolus. Bradycardia, defined as a heart rate <50 beats/min or a decrease of >20% from baseline, was treated with IV atropine 0.6 mg. A decrease in SpO₂ below 95% was treated with 100% oxygen at 6 L/min administered via an anatomical face mask with a closed circuit, as required.

Outcome measures

The primary outcome of the study was the comparison of the onset and duration of sensory and motor blockade between the two groups. The onset of sensory block was assessed every five minutes for 30 minutes until the T6 dermatomal level was achieved, and the duration of sensory and motor block was assessed postoperatively for up to 24 hours. The secondary outcome was the comparison of the VAS score and the requirement for rescue analgesia between the groups. The VAS (marked on a continuous 10-cm line, where 0 indicated no pain and 10 indicated the worst possible pain) was assessed at 30-minute intervals from 60 to 300 minutes or until rescue analgesia was administered [8]. Rescue analgesia consisted of IV tramadol 50 mg administered when patients reported a VAS score >4. The total requirement for rescue analgesia was documented. Secondary outcomes, including hemodynamic changes and adverse reactions such as nausea, vomiting, pruritus, and shivering, were also recorded.

Sample size calculation

The sample size was calculated based on the primary outcome variable, duration of postoperative analgesia, using data from the study by Athar et al. comparing intrathecal levobupivacaine and ropivacaine [9]. Assuming a two-sided alpha error of 5% (α = 0.05), a study power of 80% (β = 0.20), and the expected difference in the primary outcome derived from the previous study, the required sample size was estimated to be 45 patients in each group (total sample size = 90). During the study, one patient in the ropivacaine group experienced failed spinal anesthesia requiring conversion to general anesthesia and was therefore excluded from the per-protocol analysis. Consequently, the final analysis included 89 patients (Group L = 45; Group R = 44).

Statistical analysis

Data were analyzed using IBM SPSS Statistics for Windows, version 23.0 (released 2015; IBM Corp., Armonk, NY, USA). Microsoft Excel 2013 (Microsoft Corporation, Redmond, WA, USA) was used to create charts and diagrams. Continuous variables were expressed as mean ± SD, and categorical variables as frequency and percentage. Intergroup comparisons of continuous variables were performed using the independent Student’s t-test or the Mann-Whitney U test, as appropriate. Categorical variables were analyzed using the chi-square test or Fisher’s exact test. Because hemodynamic variables (heart rate, systolic blood pressure, diastolic blood pressure, and MAP) were measured repeatedly over time, they were additionally analyzed using repeated-measures ANOVA with Greenhouse-Geisser correction when the assumption of sphericity was violated. The analysis evaluated the effects of time, treatment group, and the time × group interaction. Bonferroni adjustment was used for pairwise comparisons where applicable. A p-value <0.05 was considered statistically significant.