A Comparison of Postoperative Analgesic Effect of Intravenous Tramadol versus Transdermal Buprenorphine Patch in Patients Undergoing Aortofemoral Graft Surgery

Introduction: The popularity of the transdermal buprenorphine patch (TDB) is currently increasing for chronic pain management because of its ease of use, non-invasive nature, sustained drug delivery, and avoidance of side effects associated with oral or parenteral routes. However, its role in postoperative pain management for aortofemoral bypass surgery is poorly established. The study was designed to compare the postoperative analgesic effect of intravenous tramadol versus transdermal buprenorphine patch in patients undergoing aortofemoral graft surgery. Objective: To compare the efficacy between a buprenorphine patch versus intravenous tramadol for postoperative analgesia in patients undergoing aortofemoral bypass surgeries.  Methods: This is a hospital-based, prospective, randomized, and interventional study. This study was conducted in the cardiac surgery Operation Theatre (OT). A total of 60 patients of either sex belonging to ASA 2 or 3 in the age group of 30-60 years and BMI ≤ 40 kg/m2 scheduled for aortofemoral bypass surgery were enrolled in this study. These 60 patients were divided into two groups; the intravenous tramadol and the transdermal buprenorphine patch group using a randomization table. Results: The two groups were comparable in terms of demographical data, duration of surgery, and time for extubation. The analysis of variance showed that the VAS score was higher in the buprenorphine group as compared to the tramadol group for the first 3 hours post operatively but after that, the VAS score was significantly less in the buprenorphine group at various study intervals. A greater number of patients complained of pain for the first 3 hours postoperatively, but after that the patients had better pain relief for the rest of the study period. Conclusion: Transdermal buprenorphine applied preoperatively is a safe and effective option for postoperative pain management as it offers superior pain control and reduces the need for rescue analgesia, thereby decreasing potential side effects as compared to intravenous tramadol.

INTRODUCTION

Post-operative pain management has always been a challenging issue despite our knowledge in the physiology of acute pain. Various methods of pain management exist including opioid and non-opioid analgesics, systemic and local delivery methods, and regional and minimally invasive techniques¹.

Many drugs and routes have been studied earlier. Transdermal drug delivery system plays a vital role in managing chronic as well as acute pain as they are easy to use, provide a constant rate of drug delivery, and maintain sustained blood levels for pain management. They can eliminate the need for parenteral or oral routes of drug administration, which can have side effects².

The buprenorphine patch is an example of a transdermal drug delivery system (TDDS) which is simple, easy to use, compliant, relatively safer, and provides sustained drug delivery. To be able to use it as a patch, buprenorphine is incorporated into an adhesive polymer matrix (acrylate vinyl acetate), which allows it to be released continuously over 7 days. The patches are available in three strengths of 5, 10 and 20 mg with drug release rates of 5, 10 and 20 mg/hour respectively³,⁴.

The buprenorphine patch has been compared with oral tramadol, but till now we could not find the comparison between the buprenorphine patch and intravenous tramadol for postoperative analgesia. This study was designed with the primary aim to compare the efficacy of buprenorphine patches to intravenous tramadol for postoperative analgesia in patients undergoing aortofemoral bypass surgeries. Also, to determine the difference in time to first rescue analgesia and the total dose of rescue analgesic required in the first 72 hours postoperatively.

METHODS

This is a prospective and randomized study, that has received ethical approval from the institutional ethics committee (Ref no. 720/MC/EC/2020). The study was registered with the Clinical Trial Registry of India (CTRI) with trial number CTRI/2021/09/036226. Written informed consent was obtained from 60 patients aged 30-60 years of either sex belonging to ASA 2 or 3 with a BMI ≤ 40 kg/m2, and undergoing aortofemoral bypass surgery. There had to be 30 cases in each group to get a 95% confidence level and 80% power to confirm the expected difference of 34% in the number of cases in each group that needed rescue analgesia within 7 days, as mentioned in the seed article⁴. The sample size calculation was based on the formula:

\( \documentclass{article} \usepackage{amsmath} \begin{document} \displaystyle N = \frac{Z^2 \cdot P(1 - P)}{d^2} \end{document} \)

N: the sample size

Z: the level of confidence

P: the expected prevalence or proportion

d: the precision

Patients who were taking medications that may interact with tramadol or buprenorphine, alcoholics or drug abusers, and those who with known drug allergies were excluded from the study. The patients were divided into 2 groups either the intravenous tramadol group (Group 1) or the transdermal buprenorphine (TDB) patch group (Group 2) using a randomization table. The patients were aware of the group they belonged to (by looking at the buprenorphine patch or IV tramadol); however, the physician assessing pain and satisfaction score was unaware of the group the patient belonged to. Hence it was a single-blinded study.

The complete process about the study drugs, post-operative pain treatment options, and pain score assessment was explained to patients a day before surgery. Patients in the buprenorphine group received a buprenorphine patch of 10 mcg/h, 18 hours before the surgery (effective serum concentration is achieved after 12-24h) which was applied to the upper outer arm⁴. A dosage of alprazolam 0.25 mg was given to all patients the night before surgery to allay anxiety. On the day of surgery, all the baseline parameters (heart rate [HR], blood pressure [BP], oxygen saturation [SpO2]) were recorded, and the intravenous (IV) line was secured. Before induction of anesthesia, IV glycopyrrolate (0.2 mg) and midazolam 0.15 mg/kg were administered to all patients. After preoxygenation, anesthesia was induced with IV midazolam 0.05 mg/kg, fentanyl 2 mcg/kg, etomidate 0.3 mg/kg, and rocuronium 0.9mg/kg to attempt intubation. Anesthesia was maintained with 60% of N₂0 and 40% of O_2,isoflurane 1-1.5%, and atracurium 0.5 mg/kg loading dose followed by 0.1 mg/kg maintenance dose. The bispectral index score was maintained between 40-60 throughout the surgery by varying the concentration of isoflurane and 1mcg/kg fentanyl. End-tidal CO2 was kept between 35 and 40 mmHg by adjusting ventilation.

The patients in the buprenorphine group were not given any other analgesic apart from their routine buprenorphine patch, whereas patients in the tramadol group did receive 100 mg tramadol at the time of skin closure, followed by 50 mg every 6 hours till 72 hours. Postoperatively, pain (using visual analogue scores 0-10), sedation score, and hemodynamic parameters were assessed at 1, 3, 6, 12, 24, 36, 48, 60, 72 hours.

Rescue analgesia in the form of 1 gram Paracetamol up to 3 times a day was given to patients whose VAS score went 4 or higher. If in any patient, pain persisted within 6 hours of giving paracetamol then diclofenac (75 mg IM) was given as a secondary rescue analgesic. Recordable side effects were lightheadedness, postoperative nausea and vomiting, and constipation.

A chi-square test or Fisher test was used to analyze categorical or nominal variables (summarized as numbers and percentages). The Fischer exact test was used when at least one of the cells in the 2x2 contingency table had an expected frequency

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