Pain, a distressing sensation often triggered by intense or damaging stimuli, has been a subject of medical inquiry and intervention for centuries. René Descartes, in 1644, proposed that pain was a disturbance transmitted along nerve fibers to the brain, a concept foundational to our understanding of pain pathways. The World Health Organization defines pain as "an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage." This definition underscores the complex and subjective nature of pain, which poses significant challenges in both its diagnosis and treatment. Pain functions as a protective mechanism, encouraging individuals to withdraw from harmful situations and safeguard damaged tissues. However, pain can persist even after the initial stimulus is removed and the body has ostensibly healed, sometimes occurring without any identifiable cause. Pain is the most common reason for physician consultations in developed countries, particularly postoperative pain, which is prevalent following surgical procedures.1-4

Postoperative pain, often resulting from tissue and nerve damage, can lead to prolonged central and peripheral hyperexcitability in nociceptive pathways. This type of pain poses significant challenges to both surgeons and anesthesiologists due to its adverse physiological and psychological effects, which can hinder the normal recovery process. Effective postoperative pain management is crucial as inadequate pain relief can lead to significant morbidity and mortality, delaying recovery and return to daily activities. Acute pain, lasting from a few days to weeks, is typically associated with a neuroendocrine response to surgical stress. In contrast, chronic pain, which can persist for months, might develop if acute pain is not adequately managed. Preemptive analgesia, administered before surgery, aims to prevent central sensitization caused by surgical and inflammatory injuries, potentially reducing immediate postoperative pain and preventing the development of chronic pain.5-9

Over the centuries, various methods have been employed to manage pain, ranging from traditional plant extracts and hypnosis to modern pharmacological interventions. Opioids like morphine and fentanyl have been mainstays in pain management, administered through various routes despite their side effects, including respiratory depression, which limits their use. Non-steroidal anti-inflammatory drugs (NSAIDs) and non-pharmacological techniques like transcutaneous electrical nerve stimulation (TENS) have also been employed, albeit with varying degrees of success. Transdermal drug delivery systems present a promising alternative by providing sustained drug release and bypassing first-pass metabolism.10-15This study aims to compare the efficacy and safety of two opioid transdermal patches, fentanyl, and buprenorphine, for postoperative pain relief in major abdominal surgeries. By evaluating their analgesic benefits and associated side effects, this research seeks to enhance postoperative pain management strategies and improve patient outcomes.

AIM AND OBJECTIVES

Aim:

The primary aim of this study is to compare the effectiveness of transdermal buprenorphine and fentanyl patches for postoperative pain relief in patients undergoing major abdominal surgeries.

Objectives:

1. To evaluate the postoperative analgesic efficacy of transdermal fentanyl and buprenorphine patches in patients undergoing major abdominal surgeries.
2. To assess the side effects and complications associated with the use of transdermal fentanyl and buprenorphine patches, attributing any observed adverse effects to the respective drug dosages.

Study Design and Setting:

This study, titled “Comparison Between Transdermal Buprenorphine and Fentanyl for Postoperative Analgesia in Major Abdominal Surgeries,” was conducted over one year in the Department of Anaesthesia and Intensive Care at Acharya Shri Chander College Of Medical Sciences And Hospital, Jammu. The study received approval from the institutional ethical committee. Ninety consenting patients of either sex, admitted for major abdominal surgeries, were enrolled after meeting the eligibility criteria.

Inclusion Criteria:

Patients who met the following criteria were included in the study:

1. American Society of Anesthesiologists (ASA) grade I and II.
2. Age between 18 and 60 years.
3. Body weight between 45 and 90 kg / Body Mass Index (BMI) 18-30 kg/m².
4. Undergoing elective laparoscopic cholecystectomy under general anesthesia.

Exclusion Criteria:

Patients were excluded based on the following criteria:

• Impaired kidney or liver function.
• History of cardiac or central nervous system disease.
• History of drug or alcohol abuse.
• History of chronic pain or daily analgesic intake.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension).
• NSAID intake within 24 hours before surgery.
• Allergy to the study medications.
• Duration of surgery exceeding 90 minutes.

Study Groups and Randomization:

Eligible subjects were randomly assigned to one of two groups using a computer-generated randomization table, each group consisting of 30 patients.

• Group I (n=30): Patients received a Buprenorphine patch (10 μg/h) applied to a hairless area of the chest, back, flank, or upper arm the night before the scheduled surgery.
• Group II (n=30): Patients received a Fentanyl patch (25 μg/h) applied to a hairless area of the chest, back, flank, or upper arm the night before the scheduled surgery.

Preanesthetic Preparation:

A preanesthetic check-up was conducted one day prior to surgery, including a detailed history, general physical examination, systemic examination, and airway assessment for all patients. Routine and specific necessary investigations were performed. Demographic data such as age, sex, weight, height, and BMI were recorded. Informed written consent was obtained from all patients during the preanesthetic evaluation. Patients were familiarized with the 10-point Visual Analogue Scale (VAS) for pain assessment, with 0 indicating no pain and 10 indicating maximum pain. All patients were kept fasting for six hours prior to surgery and received a dose of Tab alprazolam 0.25 mg and Tab pantoprazole 40 mg orally the night before surgery.

Anesthetic Technique:

Upon arrival in the operating theater, standard monitors (ECG, NIBP, Pulse oximetry) were attached, and baseline parameters (heart rate, systolic, diastolic blood pressure, mean arterial pressure) were recorded. After adequate preoxygenation, anesthesia was induced with Fentanyl 1 μg/kg and Propofol 2 mg/kg. Laryngoscopy and intubation were facilitated with Rocuronium 0.6 mg/kg. Anesthesia was maintained with a mixture of 33% Oxygen, 66% Nitrous Oxide, and 0.5-1% Isoflurane. At the end of the surgery, residual neuromuscular blockade was antagonized with Neostigmine (0.05 mg/kg) and Glycopyrolate (0.01 mg/kg), and the patient was extubated. Patients were then shifted to the post-anesthesia care unit for observation, with the arrival time in the postoperative unit defined as 0 hour postoperatively.

Evaluation Parameters:

Patients were evaluated every 30 minutes for the first 2 hours in the postoperative recovery unit, followed by monitoring at 4, 8, 12, and 24-hour intervals in the postoperative ward. The following parameters were assessed:

1. Postoperative Pain: Evaluated using the Visual Analog Scale (VAS), where 0 indicates no pain and 10 indicates the maximum intolerable pain. Patients with a VAS score above 3 received a rescue analgesic dose of diclofenac 75 mg intramuscularly, repeatable after 12 hours if required. Breakthrough pain was managed with intravenous Paracetamol 1 gm every 8 hours. The time to the first requirement of analgesia (the interval between extubation and the first analgesic dose) was recorded.
2. Sedation: Assessed using the Ramsay Sedation Score:

3. Postoperative Monitoring: Continuous monitoring of heart rate, systolic and diastolic blood pressure.
4. Side Effects: Noted any occurrences of nausea, vomiting, blurred vision, and headache.

Statistical Analysis:

Data were analyzed using ANOVA and Chi-square tests. Continuous variables were summarized as means and standard deviations, while categorical variables were expressed as frequencies and percentages. Graphical data presentations included bar and line diagrams. Analysis of variance (ANOVA) with least significant difference (LSD) tests was employed for comparing continuous variables, and Chi-square or Fisher’s exact tests were applied for categorical variables. A p-value of less than 0.05 was considered statistically significant. Data compilation and analysis were performed using Microsoft Excel and SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA).

The present study was designed to evaluate and compare the effectiveness of transdermal buprenorphine and fentanyl patches for postoperative analgesia in patients undergoing major abdominal surgeries. A total of 60 patients were enrolled and equally divided into two groups. Various parameters were assessed, including demographic and baseline characteristics, postoperative pain levels, hemodynamic stability, sedation scores, and incidence of side effects.

The demographic and baseline characteristics of the study participants were assessed to ensure comparability between the two groups. Group I (Buprenorphine) and Group II (Fentanyl) each consisted of 30 patients. The mean age of patients in Group I was 47.73 years, while in Group II it was 51.63 years, with no significant difference between the two groups (p=0.413). The gender distribution showed a higher proportion of females in Group I (73.33%) compared to Group II (50%), but this difference was not statistically significant (p=0.111). The mean weight of patients was similar between the groups, with Group I averaging 62.16 kg and Group II averaging 65.66 kg (p=0.123). Additionally, the ASA physical status distribution did not differ significantly between the groups, with most patients in both groups classified as ASA I.

Table 1: Demographic and Baseline Characteristics of Patients

Postoperative heart rate and blood pressure were monitored at various intervals to evaluate hemodynamic stability. The heart rate in both groups showed a similar trend, with a decrease from baseline until 1.5 hours postoperatively, followed by an increase and stabilization by 24 hours. There were no significant differences in heart rate between the two groups at any time point (p>0.05). Systolic and diastolic blood pressure followed a similar pattern, with an initial decrease from baseline until 1 hour, then a gradual increase and stabilization. Again, no significant differences were observed between the groups for systolic and diastolic blood pressure at any time point (p>0.05), indicating that both analgesic regimens maintained hemodynamic stability.

Table 2: Comparison of Postoperative Heart Rate and Blood Pressure Between Groups

Pain levels, as measured by the Visual Analog Scale (VAS), were recorded at various intervals postoperatively. Both groups showed an increase in VAS scores, peaking at 2 hours postoperatively, and then a steady decrease. At 24 hours, the VAS scores were similar between Group I (0.53) and Group II (0.60), with no significant differences at any time point (p>0.05). This indicates that both transdermal buprenorphine and fentanyl provided effective postoperative pain relief, with comparable efficacy in reducing pain scores over the 24-hour period.

Table 3: Postoperative Visual Analog Scale (VAS) Scores

The time to the first requirement for rescue analgesia and the number of rescue doses were recorded to assess the duration of analgesic efficacy. The mean time to the first rescue analgesic was slightly shorter in Group I (172 minutes) compared to Group II (184 minutes), but this difference was not statistically significant (p=0.44). Additionally, the distribution of the number of rescue analgesic doses was similar between the groups, with no significant difference (p=0.60). Most patients in both groups required one or two doses of rescue analgesia, indicating that both transdermal patches provided sufficient analgesia with minimal additional medication.

Table 4: Time to First Rescue Analgesic and Number of Rescue Doses

Sedation levels were assessed using the Ramsay Sedation Score at various intervals postoperatively. Group II (Fentanyl) exhibited significantly higher sedation scores than Group I (Buprenorphine) from 0 to 2 hours postoperatively (p<0.01). However, sedation scores in both groups decreased over time, with no significant differences observed from 4 hours onward. By 24 hours, both groups had a sedation score of 1.00, indicating that patients were alert and responsive. These results suggest that while fentanyl may cause higher initial sedation, both drugs result in minimal sedation by 24 hours postoperatively.

Table 5: Postoperative Sedation Scores

The incidence of postoperative side effects, including nausea, vomiting, headache, and blurring of vision, was compared between the two groups. Group II (Fentanyl) had a higher incidence of nausea (33.3%) and vomiting (26.7%) compared to Group I (Buprenorphine), though these differences were not statistically significant (p=0.06 and p=0.08, respectively). Headache was significantly more common in Group II (36.7%) compared to Group I (10.0%) (p=0.03). Blurring of vision was also more frequent in Group II (23.3%) than in Group I (3.3%) (p=0.05). These findings indicate that while both analgesics are effective, fentanyl may be associated with a higher incidence of certain side effects.

Table 6: Postoperative Side Effects

This prospective, double-blinded, randomized one-year study conducted on 60 patients at Acharya Shri Chander College of Medical Sciences and Hospital, Jammu, aimed to evaluate and compare the efficacy and safety of transdermal buprenorphine and fentanyl patches for postoperative analgesia in major abdominal surgeries. The study design ensured equal distribution, with patients randomly assigned to two groups of 30 each: Group I received a buprenorphine patch (10 μg/h), and Group II received a fentanyl patch (25 μg/h), both applied 8 hours before surgery.

The primary focus was to assess the postoperative efficacy of these transdermal patches in terms of the duration of analgesia, reduction in pain scores, total postoperative analgesic requirements, side effects, and complications. Baseline characteristics, including age, weight, and gender distribution, were comparable between the groups. The mean age was 47.7 years for Group I and 51.6 years for Group II (p=0.413). The mean weight was 62.16 kg in Group I and 65.66 kg in Group II (p=0.123). The gender distribution showed a higher proportion of females in both groups, with no significant difference (p=0.111).

Pain relief efficacy, measured using the Visual Analog Scale (VAS), indicated that both groups experienced a peak in pain at 2 hours postoperatively, followed by a steady decline. By 24 hours, VAS scores were 0.53 in Group I and 0.60 in Group II, with no significant differences at any time interval (p>0.05). This suggests that both buprenorphine and fentanyl patches provide effective pain relief for major abdominal surgeries.

The time to the first requirement of rescue analgesia was slightly shorter in Group I (172 minutes) compared to Group II (184 minutes), though this difference was not statistically significant (p=0.44). Furthermore, the amount of rescue analgesia used was similar between the groups (p=0.60), indicating comparable analgesic effectiveness.

Sedation levels, assessed using the Ramsay Sedation Score, were initially higher in the fentanyl group, with significant differences observed from 0 to 2 hours postoperatively (p<0.01). However, sedation levels in both groups normalized by 24 hours. These findings suggest that while fentanyl may cause more sedation initially, both drugs are similar in terms of sedation by the end of the first postoperative day.

Hemodynamic parameters, including heart rate and blood pressure, were stable and comparable between the groups. Mean heart rates decreased initially and then stabilized by 24 hours, with no significant differences at any time point (p>0.05). Systolic and diastolic blood pressures followed a similar pattern, further indicating that both analgesic regimens maintain hemodynamic stability.

The incidence of side effects such as postoperative nausea, vomiting, headache, and blurring of vision was higher in the fentanyl group. Nausea (33.3%) and vomiting (26.7%) were more common compared to the buprenorphine group, although not statistically significant (p=0.06 and p=0.08, respectively). However, headaches were significantly more frequent in the fentanyl group (p=0.03), and blurring of vision was more common as well (p=0.05). These findings highlight that while both drugs are effective for pain management, fentanyl may be associated with a higher incidence of certain side effects.

Transdermal drug delivery systems (TDS) offer a non-invasive, convenient, and sustained method of drug delivery, making them a preferable alternative to parenteral and oral methods. They avoid painful skin punctures, multiple dosing, and first-pass metabolism, which are significant advantages . TDS allows for continuous drug delivery, maintaining stable plasma levels and reducing the incidence of breakthrough pain and adverse effects . However, they are not extensively used for postoperative pain control due to their slower onset, unpredictable absorption during hypothermia, interpatient variability, high cost, and limited availability of drugs suitable for transdermal delivery .

The current study's findings align with previous research on the efficacy of transdermal fentanyl and buprenorphine for postoperative pain management. Gourlayet al12 demonstrated that transdermal fentanyl provides significant postoperative pain control, although supplementary doses of pethidine were sometimes required for incident pain. Lehmann LJet al15also confirmed the effectiveness of fentanyl as an analgesic via multiple routes, highlighting the promising potential of transdermal delivery for postoperative pain relief. Sandler et al16 observed that while side effects like nausea and vomiting were variable, clinically significant respiratory depression was rare with transdermal fentanyl, reinforcing its utility in postoperative settings.

Similarly, Van Lersbergheet al17 compared epidural, intravenous, and transdermal administration of fentanyl, finding almost equivalent degrees of analgesia, which supports the results of our study. Jealet al18reviewed the pharmacological properties of transdermal fentanyl and confirmed its efficacy in managing chronic malignant pain, corroborating its effectiveness for postoperative pain in our study. On the other hand, Sorgeet al19 found that transdermal buprenorphine provided adequate pain relief and improved pain intensity and duration of pain-free sleep, which aligns with our findings. Arshad et al9 compared transdermal buprenorphine and fentanyl for postoperative pain relief after abdominal surgeries, concluding that both were effective and safe, with fentanyl being slightly superior. However, our study found both drugs equally efficacious in postoperative pain relief. Santosh Kumar et al20 evaluated the efficacy of transdermal buprenorphine patches in postoperative pain management and concluded that they were effective in attenuating postoperative pain and maintaining hemodynamic stability, with fewer postoperative rescue analgesic requirements. This is consistent with our study's results.

Overall, both buprenorphine and fentanyl transdermal delivery systems are effective for postoperative analgesia with a lesser requirement for rescue analgesics. Considering cost-effectiveness, buprenorphine TDS is more favorable due to its lower cost and longer duration of action. However, fentanyl TDS provides better initial analgesia with less sedation, making it a safe and ideal option for controlling postoperative pain.

Based on our comprehensive study, it can be concluded that both buprenorphine and fentanyl transdermal delivery systems (TDS) are effective and adequate for postoperative analgesia in major abdominal surgeries, with a lesser requirement for rescue analgesics. Buprenorphine TDS, being more cost-effective and having a longer duration of action, emerges as a favorable option for sustained pain management over seven days. However, fentanyl TDS demonstrates superior efficacy in controlling postoperative pain with less sedation, making it a safer and more ideal choice for immediate postoperative pain relief. Despite some minor differences in side effects, both transdermal systems offer significant benefits in postoperative pain management, providing stable hemodynamic parameters and effective analgesia, thus ensuring patient comfort and recovery.

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