INTRODUCTION:

Many disease processes present with pain as a common feature and is associated with actual or impending tissue damage. The perioperative pain is defined as pain because of pre-existing disease, surgical procedure or a combination of these. It results in physiological and psychological responses in the patient which are detrimental to postoperative outcome.¹ Acute postoperative pain, moderate-to-severe is a problem, despite the progress in pain management. Worldwide some associations and societies like the Agency for Health Care Policy and Research (AHCPR; US), the International Association of the Study of Pain, and the Royal College of Surgeons (UK) (RCSCA 1990; AHCPR 1992; IASP 1992) have recognised pain as a debilitating factor in postoperative period.² Anxiety, sleep disturbance, demoralization, disturbed mental activity and social relations, increased heart rate and blood pressure, low immunity, decreased pulmonary functions, increased complications i.e, heart attack, deep venous thrombosis, pulmonary embolism, hypoxia, pneumonia, stroke will result from ineffectively treated and persistent postoperative pain.³ Several pain management strategies are aimed at reducing a patient’s pain to a tolerable level. A balanced analgesia uses different modalities of pain management in order to provide a pain and stress-free state, for a good postoperative outcome. The systemic opioid administration is the most and continues to be a popular technique. Opioids are generally given by intramuscular, intravenous, subcutaneous routes. The intravenous route is most common and produces prompt and predictable blood levels, which allows for a precise titration of analgesic requirements. The continuous intravenous infusion provides a steady blood level of the drug but it must be remembered that it takes a long time to achieve 95% of the final steady state concentration of the drug. Thus, intravenous infusion results in inadequate analgesia in a patient which is dealt by intermittent IV boluses. The beginning of new era has led to the development of transdermal drug delivery system which has become an integral part of pain management. Transdermal patches, though are costly but have become popular because of its advantages.⁴ They deliver a sufficient quantity of drug through the skin of the patient.⁵ The goal is to maximize the drug delivery through the skin into the systemic circulation and to minimize the retention and metabolism of the drug in the skin.⁶ It has various advantages like controlled absorption, steady plasma drug levels, improved bioavailability of the drug, minimal adverse effects, painless, ease of application and flexibility of terminating drug administration by simply removing the patch from the skin.⁴ Because of increasing patient compliance, transdermal delivery systems are advantageous over injectables and oral routes. The drug absorption occurring through the percutaneous route becomes evident by the drug levels measurable in blood, drug and its metabolites excretion through urine and through the positive clinical response of the patient.⁵ Among opioids, fentanyl is the most commonly used. It is a synthetic opioid with a low molecular weight, smaller chemical structure, soluble in both fat and water and has high analgesic property because of which it can be a good choice for transdermal route of drug delivery. The fentanyl transdermal system (Durogesic reservoir patch) is approximately in the size of a credit card. It delivers fentanyl at constant rates: 25, 50, 75, and 100 microgram/hour for 72 hours, respectively.⁷ Hence, the purpose of our study was to evaluate the efficacy of transdermal fentanyl patch with intravenous fentanyl for postoperative pain relief in patients posted for major abdominal surgeries under general anaesthesia.

MATERIAL AND METHODS:

In the Department of Anaesthesiology, Acharya Vinoba Bhave Rural Hospital, Datta Meghe Institute of Medical Sciences, Sawangi (Meghe), Wardha our prospective, randomized study was conducted between October 2019 to April 2020. The Institutional Ethical Committee approval was obtained. All the subjects in this study gave a written consent. 50 patients belonging to American Society of Anaesthesiologists Grade I and II of either gender between 20-60 years undergoing major abdominal surgeries under general anaesthesia were involved in the study after due explanation. They were randomised by computer into 2 groups each having 25 patients. Those who refused general anaesthesia, pregnant and breast-feeding women, morbid obese patients, respiratory, hepatic, cardiac and renal diseases, addiction or allergy to opioids and on chronic analgesic use were not included in the study.

The sample size was calculated using Open Epi Software by assuming an average VAS score of 3.91 and SD of 0.51, with power at 80% and a confidence interval of 95% (α error at 0.05), a sample size of 25 patients was required for the detection of a minimum of 10% difference in the mean pain score.

The study included two groups: I.V fentanyl group, Group I.V (control) and Transdermal fentanyl patch group, Group TFP (study group). The enrolled patients in Group TFP (study group) received fentanyl patch, Duragesic-25mcg/hr, 10 hours prior to the surgery on the upper arm. All the enrolled patients underwent 120-180 minutes of major abdominal surgeries i.e, exploratory laparotomy, total abdominal hysterectomy, cholecystectomy, gastrectomy; under general anaesthesia. GA was given with the standard drugs i.e, inj. Midazolam 1mg/kg, inj. Fentanyl 2mcg/kg, inducing dose of Propofol 1-2mg/kg, inj. Vecuronium 0.1mg/kg was given for intubation and maintained by 1-2% sevoflurane with 50% oxygen and 50% nitrous oxide. Neuromuscular blockade was antagonized by inj. Neostigamine 0.05mg/kg and glycopyrrolate 0.02mg/kg given at the end of surgery. Baseline readings of ECG, SPO2, NIBP, ETCO2 were noted and were monitored intraoperatively throughout the surgery and in the recovery room for 2 hours postoperatively. The patients were shifted to postoperative ward thereafter. From the time of arrival to the postoperative ward, the patients were monitored for vitals, pain by Visual Analogue Scale (VAS), sedation by Ramsay Sedation Score (RSS) and side effects i.e, nausea, vomiting, itching and respiratory depression, every 4 hours for 24 hours. The patients received inj. Paracetamol 1gm as rescue analgesic when the VAS >5. The data obtained was statistically analyzed using descriptive and inferential student’s unpaired t test and chi-square test and p-value was set statistically significant at p<0.05 with SPSS 17.0 version.

Visual analogue scale (VAS): 1-Indicating no pain. 2-Probably no pain, 3-Mild discomfort. 4-Mild pain.5-Mild to moderate pain. 6Moderate pain, 7-Increased moderate pain. 8-Moderate to severe pain, 9-Severe pain. 10-Severe to excruciating pain.

Ramsay sedation scale (RSS): 1 - anxious/restless or both 2 - cooperative, oriented and tranquil responding to command; 3 - brisk response to stimulus; 4 - sluggish response to stimulus; 5 - no response to any stimulus

RESULTS:

50 subjects who were included were randomized into two groups (Group I.V and Group TFP) with 25 patients in each group. Both the groups were comparable in demographic data. The mean age, the mean weight of the patients and the surgery duration was comparable and was statistically insignificant (Table no. 1). The mean pain intensity score observed over 24-hour postoperative period was significantly less in patients receiving transdermal fentanyl patch (Group TFP) when compared to intravenous fentanyl (Group I.V). The mean time interval for the first rescue analgesia, given when VAS>5, was longer with TFP than I.V, (Table no.2). The incidence of side effects of the drug, i.e, respiratory depression, pruritis, nausea and vomiting were significantly less in Group TFP in comparison to Group I.V, (Table no.3).

Table no.1: Demographic characteristics and duration of surgery

	Group I.V	Group TFP	p- value
Mean age of patients (years)	52.31±4.4	52.05±6.1	0.49
Mean weight of patients (kg)	65.15±10.40	67.85±8.00	0.46
Mean duration of surgery (minutes)	168.26±8.38	172.90±6.50	0.98

Table no.2: Pain score and Time of rescue analgesia

	Group I.V	Group TFP	p- value
Mean pain scores	4.67±1.18	3.80±0.12	0.012
Mean interval of rescue analgesia (minutes)	345.50±33.34	58.10±12.88	<0.0001

Table no.3: Side effects of the drug

Side effects	Group I.V (%)	Group TFP (%)
Respiratory depression	10 (40)	3 (12)
Pruritis	18 (72)	6 (24)
Nausea	21 (84)	7 (28)
Vomiting	22 (88)	6 (24)

DISCUSSION:

Opioid analgesic like fentanyl binds to specific receptors in CNS at different sites which results in increase in pain threshold, alteration of pain reception and inhibition of ascending pain pathways. In 1970, the suitability of delivery of fentanyl through the transdermal patch system was identified and has become one of the greatest commercial successes.⁸

From our study, we found that the age, weight of the patient and the surgery duration was comparable between the two groups.

In this study, we found that the pain scores, assessed by VAS, between the two groups, were not comparable suggesting that the analgesic effects of fentanyl were effective when administered by transdermal route. We also found that the time required for the first rescue analgesic was significantly higher in Group TFP in comparison to Group I.V. The number of rescue analgesics required was much less in TFP group than I.V group. Rowbotham DJ et al conducted a study where fentanyl patch was put before or within 2 hours of surgery, due to which the plateau serum levels of the drug could not take place which may be accounted for inadequate pain relief.⁹ In our study, we used a 25mcg/hour fentanyl patch applied 10 hours prior to the surgery and found it to be effective in reducing the pain.

The common adverse effects of opioids are nausea, vomiting, headache, erythema and respiratory depression. Postoperative nausea and vomiting (PONV) have a multifactorial etiology which occurs in 25% to 30% of surgeries. It leads to discomfort, distress, and dissatisfaction for the patients.¹⁰ Respiratory failure (RF) is the most serious pulmonary complication in the postoperative period.¹¹ It has been reported that 9% to 40% of the patients who undergo abdominal surgery experience postoperative pulmonary complications.¹² Many factors can change both the magnitude and duration of respiratory depression after opioid administration. In the present study, we recorded the common opioid related side effects i.e, respiratory depression, pruritis, nausea and vomiting. Sevarino et al¹³ conducted a study in which they found that the side effects i.e, depression of respiration, sedation, nausea and vomiting were higher with patches releasing 75 mcg/hr. This suggested that the adverse effects were dose dependent and that by using a lower dose of drug, the side effects could be less. In our study, we found that the side effects were significantly less with transdermal patch than with intravenous route, suggesting that transdermal system is a much safer and effective route of administration for pain relief.

CONCLUSION:

A transdermal patch of fentanyl of 25 mcg/hr put 10 hours prior to the surgery, provides an effective, safe and non-invasive method of postoperative pain relief after major abdominal surgeries. Early mobilization and increase in general health require good postoperative pain relief. The fentanyl patch has various advantages i.e, easy application to skin, low infection risk, easily available and cost effective. In conclusion, transdermal patch releasing fentanyl at 25 mcg/hr could be effectively used for postoperative analgesia in major abdominal surgeries.

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Received on 16.04.2020 Modified on 11.06.2020

Research J. Pharm. and Tech. 2021; 14(4):1915-1918.

DOI: 10.52711/0974-360X.2021.00338