Effective pain management after surgery is essential for helping patients recover and feel comfortable, especially after lower limb surgeries. One popular method used by anesthesiologists is the subarachnoid block, which is favored for its straightforward application, quick onset, and reliable results. However, there are times when longer surgeries might require switching to general anesthesia, particularly if the spinal anesthesia starts to lose its effectiveness [1]. This can be tricky during lower limb operations, where patients often have to be positioned in ways that can complicate things, like making intubation more challenging. To tackle these issues, anesthesiologists often look into using adjuvants with local anesthetics to extend the anesthesia duration and enhance the quality of the block [2,3].

Levobupivacaine, which is the S(-) form of Bupivacaine, has some notable benefits over its racemic version, such as lower risks of heart and nerve toxicity. However, since it doesn't last as long, it's important to pair it with effective adjuvants to ensure lasting pain relief. One promising option that has been researched is Butorphanol, a synthetic opioid that partially activates the mu-opioid receptor while also having mixed effects on kappa receptors [4]. When administered intrathecally, Butorphanol can lead to longer-lasting sensory and motor blockades, greater patient comfort, and fewer side effects throughout the body. Its distinct receptor activity makes it a great fit for multimodal pain management strategies, which are becoming more popular in modern anesthesia practices because they help reduce reliance on a single medication and lessen side effects [5,6].

Combining Butorphanol with Levobupivacaine for intrathecal use could create a powerful synergy, potentially enhancing both the duration and quality of spinal anesthesia while keeping hemodynamic stability intact. While earlier smaller studies hinted at the benefits of this combination, we still lack strong evidence from well-structured randomized controlled trials [7,8]. This study aims to fill that void by thoroughly assessing the effectiveness and safety of Butorphanol as an add-on to intrathecal Levobupivacaine in patients undergoing lower limb surgeries. By looking at key factors like the onset of the block, its duration, hemodynamic changes, and patient satisfaction, we hope to make a meaningful contribution to the evidence that shapes the best practices for perioperative pain management. If this combination proves to be effective, it could significantly enhance patient outcomes and become an essential part of regional anesthesia protocols for lower limb procedures.

Study Design and Setting This research was carried out as a randomized, controlled, double-blind clinical trial in the Department of Anaesthesiology at Kalinga Institute of Medical Sciences, PBMH, KIIT University, Bhubaneswar, Odisha, spanning a year. We secured ethical clearance from the Institutional Ethics Committee, and the study was officially registered with the Clinical Trials Registry of India (CTRI/2023/04/051754). We made sure to follow the guidelines set by the International Conference on Harmonization for Good Clinical Practice, along with the ethical principles laid out in the Declaration of Helsinki. Before enrolling, we obtained informed consent from all participants in their native language, using a participant information sheet and a signed or thumb-impressed consent form. Study Population We screened patients scheduled for lower limb surgeries under spinal anaesthesia to determine their eligibility. Participants had to be 18 years or older, with an American Society of Anesthesiologists (ASA) physical status of I or II, to be included in the study. We excluded patients with a history of allergy to Levobupivacaine or Butorphanol, those undergoing pain modulation therapy, or individuals suffering from complex regional pain syndrome, psychiatric conditions, or substance addiction. Sample Size and Randomization Drawing from earlier studies that looked at the regression time to the T10 dermatome, we calculated a sample size of 15 patients per group using a 95% confidence interval and 90% power, thanks to OpenEpi.com. In total, we enrolled 30 patients, splitting them evenly into two groups of 15. To ensure fairness, we randomized the participants using a computer-generated random number table. We also made sure to keep the allocation concealed by using opaque sealed envelopes. An independent anaesthesiologist, who had no role in managing the patients or collecting data, prepared the study drugs, which helped maintain the blinding throughout the research. Intervention Protocol In Group A, patients received 3.5 ml of 0.5% heavy Levobupivacaine mixed with 0.3 ml of normal saline intrathecally, while those in Group B were given 3.5 ml of 0.5% heavy Levobupivacaine combined with 0.3 ml of Butorphanol intrathecally. When the patients arrived in the operating theatre, we administered spinal anaesthesia while they were seated at the L3–L4 interspace, using a 25G Quincke spinal needle and following strict aseptic techniques. After confirming a clear flow of cerebrospinal fluid, we injected the study drug into the subarachnoid space. Once the drug was administered, we adjusted the operating table to ensure a sensory block level reached up to the T6 dermatome. Monitoring and Data Collection Before we started the anesthesia, we took some baseline measurements like heart rate, blood pressure, and peripheral oxygen saturation. We kept an eye on these parameters every five minutes during the surgery. After the operation, we evaluated pain levels using the Visual Analogue Scale (VAS), and if the score hit four or higher, we provided rescue analgesia. We also noted when the first request for pain relief came in. To assess motor function post-surgery, we used the Modified Bromage Scale, which helps us gauge how well the quadriceps are working and the extent of any motor impairment. Outcome Measures The main outcomes we focused on were the time until the first request for rescue analgesics and the postoperative pain scores measured by the VAS. On the secondary side, we looked at how long the analgesia lasted, any hemodynamic changes during the perioperative period, and the level of motor blockade as indicated by the Modified Bromage Scale. Statistical Analysis We organized the collected data using Microsoft Excel 365 and analyzed it with SPSS software version 24. Continuous variables like age, weight, duration of analgesia, and hemodynamic parameters were reported as mean ± standard deviation or median with interquartile range, depending on how the data was distributed. For normally distributed continuous variables, we used the unpaired t-test for comparisons between groups, while the Mann-Whitney U test was used for non-normally distributed data. We assessed repeated measures within groups using ANOVA or Friedman’s test, as appropriate. Categorical variables such as gender, level of block, and incidence of complications were expressed as frequencies and percentages, analyzed using the chi-square test or Fisher’s exact test. We considered a p-value of less than 0.05 to be statistically significant.

The study looked at 30 patients who were evenly split into two groups, A and B, with 15 participants in each, all undergoing spinal anesthesia. The demographics of both groups were quite similar, showing no significant differences in age, gender, weight, height, or BMI (all p > 0.05). However, Group B experienced a longer wait time between the induction of anesthesia and the start of surgery (median: 45 minutes compared to 30 minutes, p = 0.0153) and had a significantly longer surgical duration (mean: 136.7 minutes versus 84.67 minutes, p < 0.0001). When looking at postoperative outcomes, there were notable differences in the effectiveness of analgesia, the regression of sensory/motor blocks, and overall hemodynamic stability.

Table 1: Analgesia and Motor/Sensory Block Characteristics

Table 2: Surgical and Hemodynamic Comparisons

Analgesia Efficacy:

Graph 1: illustrates Group B’s prolonged analgesia duration (6.37 vs. 4.90 hrs; p < 0.0001).

Graph 2: shows Group A’s higher VAS at 6 hrs (peak: 3.6 vs. 3.07) and Group B’s higher VAS at 8 hrs.

Graph 3: confirms earlier rescue analgesia demands in Group A (100% by 6 hrs vs. 53.33%).

Sensory/Motor Block Regression:

Graph 4: demonstrates faster motor block regression in Group A (Bromage 0 by 6 hrs vs. 1.73 in Group B).

Hemodynamic Trends:

Graph 5: Comparison of SBP between Group A and Group B

Graph 6: Comparison of DBP between Group A and Group B

Graph 7: Comparison of HR between Group A and Group B

Graphs 5–7 depict SBP stabilization at ~120 mmHg in Group B (vs. ~115 mmHg in Group A), DBP declines, and HR spikes in Group B at 36 min (84.93 vs. 81.93 bpm; p = 0.0034).

Overall, Group B showed a longer duration of pain relief, a delay in the regression of sensory and motor blocks, and more stable hemodynamics, even though the surgeries took longer. In contrast, Group A needed rescue analgesia sooner and experienced a quicker resolution of the block. These findings really emphasize the importance of the intervention in Group B for extending pain relief.

The current study set out to assess how effective Butorphanol is when used alongside intrathecal Levobupivacaine for patients undergoing lower limb surgeries. The findings showed that adding Butorphanol significantly improved both the quality and duration of pain relief compared to using Levobupivacaine on its own. While factors like age, gender, body mass index, and ASA physical status were similar between the two groups, we did see some notable differences in both intraoperative and postoperative results. Group B, which received the combination of Levobupivacaine and Butorphanol, experienced a much longer duration of sensory and motor blockade, along with a significantly lower Visual Analogue Scale (VAS) score during the early postoperative phase [9]. One particularly interesting result was the longer duration of postoperative pain relief in Group B, averaging 6.37 hours compared to just 4.90 hours in Group A. This finding corresponds with the lower VAS scores recorded at 6 and 8 hours after surgery in Group B, suggesting better pain management. Moreover, fewer patients in Group B needed additional pain relief within the first six hours post-surgery, which further highlights Butorphanol's effectiveness in extending pain relief. These advantages in pain management are likely due to Butorphanol's unique pharmacological properties, especially its activity as a κ-opioid receptor agonist that provides strong spinal analgesia, along with its partial μ-opioid receptor antagonism that helps reduce common side effects associated with opioids, such as nausea, vomiting, and respiratory depression [10]. When it comes to the regression of sensory and motor blocks, Group B experienced a delay, as shown by their higher Modified Bromage Scale scores at the 6-hour mark and the fact that nearly half of the patients still had sensory block at the T10 level. This extended block might lead to longer-lasting pain relief, but it also raises some concerns in situations where early mobilization is important. Even with the prolonged block, both groups maintained stable hemodynamic parameters, although Group B did show slightly better stability in systolic blood pressure and heart rate at certain times. These results indicate that adding Butorphanol doesn’t compromise cardiovascular safety, which is crucial, especially for patients receiving spinal anesthesia [11,12]. The results of this study align with previous research. For instance, Erdil et al. found that adding opioids to intrathecal Levobupivacaine improved the duration of sensory blocks. Likewise, studies by Singh et al., Reddy et al., and Kumar et al. have shown that Butorphanol as an adjuvant leads to delayed pain relief requests and better pain management. However, some trials, like the one by Gupta et al., reported different outcomes, indicating that Butorphanol didn’t significantly extend block duration when paired with Bupivacaine. These differences could be due to variations in the local anesthetic used, the types of surgical procedures, or the dosing methods [13]. Levobupivacaine, being the pure S(–)-enantiomer of bupivacaine, has a distinct advantage thanks to its favorable pharmacological characteristics. Its lower affinity for cardiac sodium channels and higher protein-binding capacity mean there’s a reduced risk of cardiotoxicity, making it a safer choice for spinal anesthesia, especially for patients with heart issues. The use of Levobupivacaine in this study helped maintain overall hemodynamic stability in both groups, further supporting its clinical effectiveness [14]. While the results of the study are promising, there are a few limitations that we need to keep in mind. For one, the sample size was relatively small and the study was conducted at a single center, which might affect how widely we can apply these findings. Plus, the focus was mainly on short-term pain relief, without looking into long-term neurological impacts or important patient-centered factors like how quickly patients could get moving again or their overall satisfaction. Also, by excluding ASA III and IV patients, the results may not be relevant for those who are less healthy going into surgery [15]. Considering these limitations, it would be beneficial for future research to involve larger, multicenter studies with longer follow-up times. Comparing various opioid and non-opioid adjuvants, along with looking at functional recovery and what patients report about their experiences, would give us a fuller picture of the pros and cons of Butorphanol in regional anesthesia. Additionally, pharmacodynamic studies could help clarify how Butorphanol interacts with Levobupivacaine, which would aid in fine-tuning dosing strategies and making them more applicable across different surgical situations.

This double-blind, randomized controlled trial showed that adding Butorphanol to intrathecal Levobupivacaine can significantly enhance postoperative pain relief for patients undergoing lower limb surgeries. Those in Group B, who received the combination, enjoyed a notably longer duration of pain relief, lower VAS scores, and a reduced need for additional pain medication compared to Group A. The sensory blockade lasted significantly longer without affecting hemodynamic stability, which confirms the safety and effectiveness of this combination. However, the delay in motor recovery is a point of caution, especially in situations where early mobilization is crucial, like in outpatient procedures. These results highlight the potential of Butorphanol as a valuable addition to spinal anesthesia, but more extensive, multicenter studies are needed to fine-tune dosing strategies and assess long-term effects.

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