European Journal of Cardiovascular Medicine

Subarachnoid block remains one of the most widely practiced and effective regional anesthetic techniques for both elective and emergency cesarean sections, lower abdominal surgeries, and lower limb orthopedic and urological procedures.(1) Its popularity is attributed to several advantages, including low cost, maintenance of patient consciousness, rapid onset of action, quick recovery, and the absence of airway manipulation requirements.(2)

The duration of postoperative analgesia following spinal anesthesia can be enhanced by adding a small dose of an opioid as an adjunct to the intrathecal local anesthetic solution. Intrathecal opioids act synergistically with local anesthetics, enhancing the intensity and duration of sensory blockade without significantly affecting sympathetic function.(3) Opioids exert their analgesic action through the activation of opioid receptors located in the dorsal gray matter of the spinal cord, which modulate the transmission of nociceptive signals from afferent pain fibers.(4) However, when administered through systemic routes, opioids are frequently associated with undesirable side effects such as respiratory depression, sedation, hypotension, bradycardia, nausea, and vomiting.(5)

In light of this, the American Society of Anesthesiologists (ASA) recommends the use of neuraxial opioids over parenteral opioids for postoperative analgesia following neuraxial blocks (6). Buprenorphine, a long-acting, lipid-soluble, mixed agonist–antagonist opioid, has gained prominence for its ability to extend postoperative analgesia for 12–15 hours when used intrathecally, without causing significant hemodynamic instability such as hypotension or bradycardia. It is a potent centrally acting analgesic derived from the morphine alkaloid thebaine and belongs to the 6,14-endo-ethanotetrahydrooripavine class of compounds, which also includes highly potent agonists such as diprenorphine and etorphine.

Buprenorphine undergoes N-dealkylation primarily in the liver by CYP3A4 and, to a lesser extent, by CYP2D6, as well as by the intestinal mucosa, resulting in the formation of its major active metabolite norbuprenorphine along with minor glucuronide conjugates. Concomitant administration of CYP3A4 inducers such as ritonavir, amiodarone, ketoconazole, and erythromycin can lower serum levels of buprenorphine. Regardless of the route of administration, elimination occurs mainly via the gastrointestinal tract, with approximately two-thirds of the drug excreted through feces.(7) . The unique molecular structure of buprenorphine allows it to be formulated for various routes of administration, including intrathecal, intravenous, intramuscular, sublingual, and transdermal delivery. Transdermal drug delivery systems (TDDS) offer a noninvasive, convenient, and sustained-release method of administration. In the transdermal formulation, buprenorphine is embedded within an adhesive polymer matrix (acrylate–vinyl acetate), from which it is continuously released into systemic circulation over seven days. Commercially available transdermal patches come in strengths of 5 mg, 10 mg, and 20 mg, providing corresponding drug release rates of 5 μg/h, 10 μg/h, and 20 μg/h, respectively (8).

Aim of the study was to compare the effects of intrathecal injection of buprenorphine and buprenorphine transdermal patch on postoperative analgesia in patients undergoing lower abdominal surgeries under spinal anesthesia.

simple randomized double-blind study was conducted in the Department of Anaesthesia at Khaja Banda Nawaz Teaching and General Hospital, Kalaburagi, after obtaining approval from the Institutional Ethical Committee. Written informed consent was obtained from all participants prior to inclusion in the study. The study was carried out over a period of 18 months, from December 1, 2019, to May 30, 2021.

Sample Size and Study Population: A total of 130 patients aged between 18 and 60 years, belonging to the American Society of Anesthesiologists (ASA) physical status I and II, scheduled for elective lower abdominal surgeries under spinal anaesthesia, were enrolled. The sample size was calculated using standard statistical parameters: α = 0.05 (95% confidence level) and β = 0.2 (80% study power). Based on reference data from the study “Intrathecal buprenorphine versus fentanyl as adjuvant to 0.75% ropivacaine in lower limb surgeries” by Arvinder Pal Singh, and using a standard deviation (σ) of 0.17 with a minimum mean difference (µ₂–µ₁) of 0.35, the calculated sample size was 65 patients per group, totaling 130 subjects.

Inclusion Criteria: Patients aged 18–60 years, ASA grade I and II, scheduled for elective lower abdominal surgeries under spinal anaesthesia with anticipated duration less than 2.5 hours, and those who provided informed consent were included.

Exclusion Criteria: Exclusion criteria included pregnant and lactating women; patients on sedatives, hypnotics, antidepressants, corticosteroids, or other drugs affecting the nervous system; patients with chronic pain syndromes or those who had taken analgesics within the past 48 hours; patients with contraindications to spinal anaesthesia; those with failed or inadequate spinal block; and patients allergic to the study drugs.

Group Allocation: Using a computer-generated randomization list, patients were divided into two groups of 65 each.

• Group I (Intrathecal Group): Received 3 ml of 0.5% hyperbaric bupivacaine with 60 µg buprenorphine intrathecally, along with a placebo patch applied 24 hours before surgery.
• Group T (Transdermal Group): Received 3 ml of 0.5% hyperbaric bupivacaine with 0.2 ml normal saline intrathecally, along with a buprenorphine transdermal patch (10 µg/h) applied 24 hours before surgery. The patch was applied over the lateral aspect of the upper arm, chest, or upper back.

Preoperative Evaluation: All patients underwent detailed pre-anaesthetic assessment including demographic details, medical and drug history, comorbidities, and personal habits. General and systemic examinations were done, and height, weight, and BMI were recorded.

Investigations and Monitoring: Routine investigations (CBC, renal function, RBS, urine analysis, ECG, chest X-ray) were performed. Standard intraoperative monitoring with NIBP, ECG, SpO₂, and respiratory rate was initiated, and baseline vitals were recorded.

Anaesthetic Technique: Patients were kept NPO for six hours, preloaded with Ringer lactate (10 ml/kg), and an 18G IV line was secured. Spinal anaesthesia was given under aseptic precautions in the L3–L4 interspace using a 25G Quincke needle. After confirming free CSF flow, the study drug was administered as per group allocation, followed by supine positioning and block assessment.

Assessment of Sensory and Motor Block: Sensory block onset was defined as the time from intrathecal injection to loss of pinprick sensation at the T10 dermatome, assessed bilaterally using a 25G sterile needle. The duration was measured from onset to two-segment regression. Motor block was evaluated using the Modified Bromage Scale (0–3), where 0 indicated no block and 3 indicated complete block. Onset was the time to achieve a Bromage score of 3, and duration was until recovery to score 0.

Intraoperative Monitoring and Management: Heart rate, blood pressure, respiratory rate, and oxygen saturation were monitored every 2 minutes for the first 10 minutes, then every 5 minutes thereafter. Hypotension (>20% fall in SBP) was managed with fluids and phenylephrine 50 µg IV. Bradycardia (<50 bpm) was treated with atropine 0.6 mg IV, and respiratory depression (RR <8/min or SpO₂ <94%) was managed with oxygen supplementation.

Application of Transdermal Patch: The patch was applied to clean, dry skin on the upper arm, chest, or upper back, pressed firmly for 15 seconds, and reinforced if loose. It was replaced every 7 days or if detached, and disposed of safely as per manufacturer’s instructions.

Postoperative Monitoring: Surgery commenced after achieving T6 sensory level and Bromage score 3. Patients were monitored for block regression, hemodynamic stability, and adverse effects such as nausea, vomiting, pruritus, shivering, hypotension, or respiratory depression. Postoperative analgesia duration was recorded from intrathecal injection to the first request for rescue analgesic.

Statistical Analysis: Data were analyzed using IBM SPSS version 20.0 software. Qualitative data were compared using the Chi-square test, while quantitative variables were analyzed using the unpaired t-test and ANOVA as appropriate. A p-value <0.05 was considered statistically significant.

Table 1: Age and Sex Distribution of Patients in Both Study Groups

The study included 130 patients, equally divided into two groups (n=65 each). The majority of participants in both groups were in the 20–30-year age range (35.3% in Group I and 36.9% in Group T). The mean age was comparable between the groups (39.45 ± 10.97 years in Group I and 39.14 ± 10.76 years in Group T), indicating homogeneity in age distribution. Similarly, both groups had an identical sex distribution, with 60% males and 40% females, showing that the study population was well-matched demographically (Table 1).

Table 2: Distribution of Type of Infraumbilical Surgeries in Both Study Groups

The distribution of infraumbilical surgeries was identical in both groups, ensuring comparability between them. Appendectomy was the most common procedure performed (46.1%), followed by hydrocele repair (18.4%), inguinal hernia repair (15.3%), hysterectomy (12.3%), and intertrochanteric (IT) fracture fixation (7.6%). This uniform distribution indicates that the surgical profile of patients was well-balanced across both study groups, minimizing procedural bias in the evaluation of analgesic efficacy (Table 2).

Table 3: Comparison of Sensory and Motor Block Between Group I and Group T

The onset times for both sensory and motor blocks were comparable between the two groups. The mean time for sensory block was 6.94 ± 2.03 minutes in Group I and 7.00 ± 2.03 minutes in Group T, showing no significant difference. Similarly, the mean time for motor block was 5.65 ± 1.29 minutes in Group I and 5.74 ± 1.30 minutes in Group T. This indicates that both intrathecal and transdermal administration of buprenorphine produced a similar onset of sensory and motor blockade when used with bupivacaine under spinal anaesthesia (Table 3).

Table 4: Comparison of Sensory and Motor Block Time and Duration Between Group I and Group T

Mann–Whitney test; P < 0.05 considered significant; ns = not significant.

There was no statistically significant difference between the two groups in terms of onset time or duration of sensory and motor blockade. The mean sensory block time was nearly identical in both groups (6.94 ± 2.03 minutes in Group I vs. 7.00 ± 2.03 minutes in Group T), and similar results were observed for motor block time and duration. This indicates that the route of buprenorphine administration—whether intrathecal or transdermal—did not significantly influence the onset or duration of sensory and motor block when combined with bupivacaine under spinal anaesthesia (Table 4).

Table 5: Comparison of Peak Sensory Levels Between Group I and Group T

Fisher’s exact test; P < 0.05 considered significant; ns = not significant.

The peak sensory level achieved was comparable between both groups. The majority of patients in Group I (58/65) and Group T (58/65) attained a T6 sensory level, while a few reached T5 or T7 levels. Statistical analysis using Fisher’s exact test showed no significant difference (P > 0.9999) between the two groups, indicating that both intrathecal and transdermal buprenorphine provided a similar extent of sensory block when used with bupivacaine under spinal anaesthesia (Table 5).

Table 6: Comparison of Baseline Vital Parameters (24 Hours Before Application of Transdermal Patch) Between Group I and Group T

All patients in both groups exhibited normal baseline vital parameters 24 hours before the application of the transdermal patch. Pulse rate, systolic and diastolic blood pressure, and oxygen saturation (SpO₂) values were within normal ranges, with no abnormalities noted. This indicates that the study population in both groups was hemodynamically stable and comparable at baseline before administration of the study drugs (Table 6).

Figure 1: Comparison of Pulse Rate Between Group I and Group T After Spinal Anaesthesia

The graph1 illustrates pulse rate variations over time in both study groups following spinal anaesthesia. Initially, both groups showed a similar pulse rate trend, with mild elevation during the first few minutes (peak at 5 minutes). Between 10 and 45 minutes, Group T (Transdermal Patch) maintained slightly higher pulse rates compared to Group I (Intrathecal Buprenorphine), and this difference was statistically significant at several intervals. Beyond 60 minutes, pulse rates stabilized and remained comparable between groups throughout the observation period up to 150 minutes. Overall, both groups demonstrated stable hemodynamic profiles, with no clinically significant bradycardia or tachycardia episodes noted.

Figure 2: Comparison of Systolic Blood Pressure Between Group I and Group T After Spinal Anaesthesia

The graph 2 shows systolic blood pressure trends in both groups following spinal anaesthesia. Initially, both groups exhibited similar baseline and early postoperative systolic pressures. A mild, transient fall in systolic BP was observed in both groups between 5 and 35 minutes, more pronounced in Group T, though statistically insignificant. After 40 minutes, systolic values gradually stabilized and remained steady throughout the observation period up to 150 minutes. Overall, both groups maintained stable hemodynamics with no significant intergroup difference (P > 0.05).

Figure 3: Comparison of Diastolic Blood Pressure Between Group I and Group T After Spinal Anaesthesia

The graph 3 illustrates the variation in diastolic blood pressure (DBP) between the two groups following spinal anaesthesia. Both groups demonstrated stable baseline readings with a transient decrease in DBP noted around 5–35 minutes post-induction, more evident in Group T. This reduction was statistically significant at the 5-minute mark (p < 0.0001) but not thereafter. Beyond 40 minutes, DBP values stabilized and remained consistent between groups for the rest of the observation period. Overall, both techniques maintained hemodynamic stability without clinically significant hypotension.

Figure 4: Comparison of SpO₂ Levels Between Group I and Group T After Spinal Anaesthesia

The graph 4 shows oxygen saturation (SpO₂) levels in both groups throughout the postoperative monitoring period. SpO₂ values remained consistent and stable in all patients, averaging around 96.9% ± 0.76, with no desaturation episodes observed. There was no statistically significant difference between Group I (Intrathecal Buprenorphine) and Group T (Transdermal Patch) at any time point (p > 0.9999). This indicates that both methods maintained adequate oxygenation and respiratory stability following spinal anaesthesia.

Table 7: Comparison of VAS in between two groups

Mann Whitney test, P<0.05 = significant, ns= not significant. IQR = interquartile range

There was statistically significant (P<0.05) difference in VAS,  lower in GroupT compared to group I , during surgery from 2 hour till 4 hours and at 24 hour post op period in between two groups (Table 7).

Table 8: Comparison of Ramsay Sedation Score in between two groups

Mann Whitney test, P<0.05 = significant, ns= not significant. IQR = interquartile range

There was statistically  significant (P<0.05) difference in ramsay sedation score,  lower in Group T compared to group I, during surgery from 1 hour till 9 hours and at 24 hours post op period in between two groups. It was not statistically significant (P>0.05) at 12,48 hour and 72 hour post op (Table 8).

Table 9: Number of cases requiring 1^st Rescue analgesia in between two groups at different time intervals

Fisher's exact test, P<0.05 = significant, ns= not significant, *n=Number of patients

Table 9 shows, the need of rescue analgesia was seen early in Group I at 2, 3,4 hours where in no rescue analgesia was required at same hour in Group T (p= <0.0001,<0.0001,0.0132 respectively). There was requirement of rescue analgesia in Group T at 12 and 24 hours compared to Group I, (p= 0.0062,<0.0001 respectively).

Table 10: Total dose of analgesia received in this 72hours

In our study in group I 300mg analgesic was given in 32.3% cases and 200mg in 55.3% and 150mg in 2.3% cases. In our study In group T    50mg analgesic was given in 87.6% cases and 100mg in 3% (Table 10).

Table 11: Comparison of incidence of side effects between two groups.

Fisher's exact test, P<0.05,** = significant, ns= not significant, IQR = interquartile range, n=Number of patients

Table 11 shows that, the occurrence of hypotension & bradycardia was more in group I (n=25) ,(n= 30)compared to Group T (n=7) (n=15) respectively, which was statistically significant. occurrence of sedation was more in group T (n=12) ,compared to Group T (n=0) respectively, which was statistically significant. There was no significant occurrence of vomiting’s and nausea between two groups, overall the appearance of side effects was statistically significant in Group T compared to Group I(P= <0.0001).

In this study, patients who received a transdermal buprenorphine patch 24 hours before surgery experienced better postoperative pain relief compared to those given intrathecal buprenorphine. However, earlier application of the patch was associated with preoperative side effects such as sedation, nausea, and vomiting. Postoperative pain remains one of the most common and distressing experiences among surgical patients, affecting up to 80% of them, with 86% reporting moderate to severe pain. Inadequate pain control delays recovery, prolongs hospitalization, and can adversely affect surgical outcomes. The transdermal drug delivery system (TDDS) is a safe, non-invasive, and effective method that provides continuous and sustained plasma drug levels, reducing breakthrough pain and the need for rescue analgesics. Its steady release avoids sudden rises in plasma concentration and lowers adverse effects.

In the present study, most patients were between 20–30 years in both groups, with similar mean ages, heights, and weights, comparable to findings by Borse et al. (9), Rashmi et al. (10), and Safiya et al. (11), who also reported no significant demographic differences. The onset of sensory block within eight minutes occurred in 61.5% of Group I and 60% of Group T, with both reaching a maximum T6 level within this period. The mean onset time was 4 minutes in Group I and 8 minutes in Group T, showing no significant difference (P > 0.05). These findings are consistent with Borse et al., who noted similar sensory block characteristics between groups. The onset of motor block was also comparable, occurring within six minutes in about two-thirds of patients in both groups, and this aligns with the results of Borse et al., where complete motor blockade was achieved in all patients.

The duration of sensory block was similar between both groups (4.708 ± 1.343 h in Group I vs. 4.662 ± 1.35 h in Group T), with no statistical difference, consistent with Safiya et al. Hemodynamic parameters showed no significant intergroup differences except for a transient fall in systolic blood pressure intraoperatively in Group I. These findings are in agreement with Safiya et al., Borse et al., and Capogna et al. (12), all of whom reported stable pulse rate, blood pressure, and oxygen saturation during surgery.

Pain assessment by VAS showed significantly lower scores in Group T during 2–4 hours intraoperatively and at 24 hours postoperatively, indicating better analgesia with the transdermal patch. Rashmi et al. and Capogna et al. similarly found prolonged pain-free intervals and reduced analgesic requirement in buprenorphine groups. Yadav et al. also reported mild to moderate pain with gradual decline by 72 hours, matching the present trend. Sedation scores were higher in Group T, significant up to 9 hours and at 24 hours postoperatively, similar to Safiya et al., who also observed higher sedation with buprenorphine use.

Regarding complications, hypotension and bradycardia were more common in Group I, whereas sedation was more in Group T. Nausea and vomiting occurred at similar rates in both groups. These findings correlate with studies by Borse et al., Capogna et al., and Safiya et al., which reported minimal side effects and hemodynamic stability. Yadav et al. noted rescue analgesic demand peaking at 8–12 hours, similar to the present observation where the transdermal patch required fewer rescue doses over 24 hours. Kumar et al. (14) also reported that nausea was the most frequent but non-significant postoperative complication across groups.

In conclusion, the transdermal buprenorphine patch (10 μg/hour) applied 24 hours before surgery provided longer and more effective postoperative analgesia with better hemodynamic stability and lower pain scores than intrathecal buprenorphine (60 μg). Although it caused slightly higher sedation, it reduced the need for postoperative rescue analgesics and offered consistent pain control, confirming its efficacy as a safe and convenient option for postoperative pain management in lower abdominal surgeries.

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