Comparing the Efficacy of Fentanyl Nasal Packing on Postoperative Pain in Patients Undergoing Nasal Surgeries Versus Normal Saline Pack—A Randomized Control Trial

Abstract

Nasal packing following nasal procedures are commonly used to reduce post operative bleeding and pain. Removal of nasal pack may be associated with mucosal injury which may cause delayed recovery. Various aspects of post-operative pain management have been studied. Opioids such as fentanyl, morphine and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative pain. Fentanyl used topically results in a longer duration of action with a lower dosage and fewer adverse effects than IV therapy. To compare the efficacy of Fentanyl-soaked Nasal Packing on post operative pain in patients undergoing Nasal surgeries versus normal saline pack. A randomized control trial conducted among patients undergoing Nasal Surgery in the age group between 20 to 50 years at a tertiary care centre, Puducherry, India. Patients were randomly divided into two groups with 34 participants in each. Group A received Postoperative Nasal pack with 50mcg of Fentanyl and group B received Postoperative Nasal pack with Normal saline. Data were analysed using SPSS 21. The mean RSS score was 2.03 ± 0.83 and 1.38 ± 0.49 in group A and B respectively. The RSS score was significantly higher among group A than B. At all hours, mean Verbal pain intensity scale and numeric pain rating scale were significantly lower among Group A than B. At 1, 6,12 and 36 hours, Wong-Baker pain rating scale was significantly lower among Group A than B. There was no significant difference in hemodynamic parameters between the groups. The fentanyl group experienced much less postoperative pain without experiencing any significant adverse effects. We propose that applying topical fentanyl to nasal packs may be a feasible strategy to alleviate discomfort during the initial phases of recovery following nasal surgery.

Introduction

Nasal packing is used after nasal procedures to minimise postoperative bleeding and prevent patients from aspirating blood during the healing phase. In India, it is customary routine to pack the nasal cavities tightly for at least a day, and commonly for up to three to five days, following standard sinus surgery. Many surgeons regularly pack the nose whether or not there has been significant intraoperative bleeding. Postoperative nasal packing causes nasal obstruction, postnasal discharge, headache, nose pain, epiphora, and dry mouth, all of which have a detrimental influence on quality of life [1, 2]. There is a modest risk of toxic shock syndrome in people who use a nasal pack for a lengthy period of time [3].

When the nasal pack is removed, the patient suffers nasal irritation, bleeding, and anxiety. According to research, the removal of a nasal pack is the most unpleasant component of the perioperative phase for patients [4, 5] Nasal packing removal techniques may cause mucosal injury, which may cause recovery to be delayed and increase the risk of synechiae and scarring [6]. As an analgesic, a variety of opioids can be delivered via the practical intranasal route. Intranasal fentanyl (INF), a highly lipophilic step 3 opioid on the WHO Ladder, has lately been shown to have a very quick analgesic impact in surgical pain, acute pain in emergency departments, procedural wound care pain, paediatric premedication, and cancer-related breakthrough pain [7–9].

Fentanyl can be applied topically and absorbed transmucosally because of its lipophilic nature, resulting in a longer duration of action with a lower dosage and fewer adverse effects than IV therapy [10]. In contrast to the 3-h half-life of intravenous fentanyl, it is known that fentanyl administered subcutaneously has a terminal half-life of more than 10 h [11]. Furthermore, topical fentanyl pain treatment for the nose has few systemic side effects, a low plasma concentration, little first-pass effects, and great patient tolerance [12]. This is because systemic analgesia is less effective than fentanyl's agonistic activities on opioid receptors in the ethmoid nerve and maxillary nerve in nasal tissues [13]

Sudies have shown that, unlike IV fentanyl, INF has a similar analgesic effect while without inducing respiratory depression or affecting vital markers such as heart rate or blood pressure [14]. Mucosal fentanyl is a potential alternative to traditional analgesic administration strategies for reducing postoperative pain. According to recent research by Apuhan et al., rehydrating merocel packing with levobupivacaine or prilocane solution is a straightforward, inexpensive, safe, and effective analgesic therapy for patients undergoing nose surgery [15]. Nasal packing rehydration may give great analgesia during packing removal, which has been known to induce considerable pain. Although prilocaine and levobupivacaine caused statistically significant differences in visual analogue score (VAS) and Ramsay sedation scores (RSS), fentanyl is a short-acting synthetic opioid with a pharmacokinetic profile better suited for rapid relief of brief episodic pain, as well as being longer-acting and less expensive than lidocaine.

Objectives

1. To estimate the efficacy of fentanyl nasal pack on postoperative pain in patients undergoing nasal surgeries.

2. To compare whether there is reduction in post-operative pain in patients undergoing nasal surgeries with fentanyl-soaked nasal pack versus normal saline.

Material and Methods

Study Design

This was a double blinded randomized control trial.

Study Setting

This study was conducted in a tertiary care teaching hospital, Puducherry, India.

CTRI Registration no. CTRI/2023/05/052299.

Study Participants

Inclusion Criteria

This study was conducted among the patients undergoing Nasal Surgery for Endoscopic polyp removal, Nasal bone reduction surgery and septoplasty among patients with age between 20 and 50 years and those who were willing to participate.

Exclusion Criteria

Patient with respiratory disorders, psychiatric disorders, bradycardia/cardiac anomalies, migraine/vascular headache were excluded.

No of Groups Studied

Group A

Postoperative Nasal pack with 50 mcg of Fentanyl.

Group B

Postoperative Nasal pack with Normal saline.

Sample Size Calculation

The sample size 68 (34 in each group) was calculated based on similar study by Kim et al. [16] with the expected mean difference in NPRS as 0.69 and the standard deviation of 0.86. The level of significance and power were taken as 5% and 90% respectively

$$\frac{\text{M}{\left(\text{Z}1-\alpha /2+\text{Z}1-\beta \right)}^2\times 2{\text{S}}^2}{{\mathrm{\Delta }}^2}=\frac{{\left(1.96+1.28\right)}^2\times 2{\left(0.8\right)}^2}{{\left(0.69\right)}^2}$$

 = 68 (where ‘S’ is the standard deviation)

Sampling Method

Convenience sampling method was used to collect the samples.

Randomization

After convenience sampling, patient will be randomized by the closed envelope technique into 2 groups. Group A received 50 mcg of Fentanyl pack and Group B received plain pack with 0.9% isotonic saline.

Data Collection

The study was started after obtaining Institutional ethics approval. The purpose and procedure of the study was explained to the enrolled participants in their local language. Patient information sheet and informed written consent were obtained from the participants before initiating the study. Assessment of pain was done at frequent intervals (1,3,6,12,24,36 h) after surgery respectively by using Ramsay sedation scale and numeric rating scale.

Ethical Consideration

Institutional Ethics Committee approval was obtained before starting the study. The participants were explained that the data collected in this study will be used only for research purposes. The participants were explained about their freedom to withdraw from the study at any time without penalty or loss of benefits. The confidentiality of the data collected from the enrolled participants was maintained in all the phases of the study. The study participants who required medical attention during the period of intervention was given appropriate medical care.

Statistical Analysis

The collected data were checked for completeness before entering into the Microsoft excel spread sheet. The validation of the data was checked at regular intervals. Data analysis was performed using Statistical Package for Social Sciences (SPSS IBM) 21. The quantitative data was expressed in proportions. Mann Whitney U test, Kruskal Wallis test were applied to compare the scores. P value of less than 0.05 was considered significant.

Results

The mean age of the study participants was 33.29 ± 8.05 and 31.68 ± 7.58 in group A and group B respectively. There was no statistically significant difference in the age among the groups (p = 0.387). In group A, 50% of the study participants were males and 50% were females. In group B, 44.1% and 55.9% of the study participants were males and females respectively. There was no statistically significant difference in gender between the groups (p = 0.627). The mean BMI of the study participants was 24.21 ± 1.52 and 24.37 ± 1.45 in group A and group B respectively. Nasal discharge (70.6%) was seen more frequently in Group A patients followed by sneezing and anosmia whereas nasal obstruction (55.9%) was seen more in group B patients followed by anosmia as shown in Fig. 1. Patients included in our study underwent FESS, Septoplasty, Endoscopic Polyp removal, Nasal bone reduction surgery as a procedure as shown in Table 1. Hypertension was seen among 41.2% and 47.1% in group A and B respectively. Diabetes mellitus was seen among 55.9% and 32.4% in group A and B respectively.

Fig. 1.

Distribution of symptoms in the study participants

Table 1.

Procedure done in the study participants

Procedure	Group A (n = 34)		Group B (n = 34)		P value
	N	%	N	%
FESS	8	23.5	11	32.4	0.309
Septoplasty	13	38.2	6	17.6
Endoscopic polyp removal	4	11.8	5	14.7
Nasal bone reduction surgery	9	26.5	12	35.3

Headache was observed in 14.7% and 23.5% among group A and B respectively and 17.6% and 23.5% had sore throat after surgery in group A and B respectively. There was no significant difference in symptoms after surgery among the groups. Post-operative IV fentanyl was used in 23.5% and 29.4% patients in group A and B respectively. There was no significant difference in IV fentanyl usage between the groups. Only 20.6% in group A had post-operative IV NSAID usage, whereas 38.2% in group B had post-operative IV NSAID usage. The mean RSS score was 2.03 ± 0.83 and 1.38 ± 0.49 in group A and B respectively. The RSS score was significantly higher among group A than B. The mean verbal pain intensity scale was observed at 1, 3, 6,12, 24- and 36-h post-surgery. Our study found that the mean verbal pain intensity scale scores were less in group A than group B during all observation period as shown in Table 2. Similarly Numeric pain rating scale was also done and observed a statistically significant lower scores in group A than group B as shown in Table 3. The Wong-Baker pain rating scale was statistically lower in Group A than B at 1, 6, 12, and 36 h as shown in Table 4.

Table 2.

Verbal pain intensity scale in the study participants

Verbal pain intensity scale	Group A (n = 34)		Group B (n = 34)		P value
	Mean	SD	Mean	SD
1 h	4.53	0.51	5.65	0.49	< 0.001
3 h	3.82	0.83	4.79	0.84	< 0.001
6 h	3.00	0.70	4.21	0.81	< 0.001
12 h	2.50	0.51	2.97	0.83	.017
24 h	1.88	0.84	2.44	0.50	.004
36 h	1.38	0.49	1.97	0.90	.006

Table 3.

Numeric pain rating scale in the study participants

Numeric pain rating scale	Group A (n = 34)		Group B (n = 34)		P value
	Mean	SD	Mean	SD
1 h	7.03	0.80	7.91	0.62	< 0.001
3 h	5.85	0.89	7.03	0.80	< 0.001
6 h	4.91	0.75	5.74	0.83	< 0.001
12 h	4.09	0.87	5.21	0.84	< 0.001
24 h	2.85	0.82	3.74	0.86	< 0.001
36 h	1.91	0.79	2.50	0.51	.002

Table 4.

Wong-Baker FACES pain rating scale in the study participants

Wong-Baker FACES pain rating scale	Group A (n = 34)		Group B (n = 34)		P value
	Mean	SD	Mean	SD
1 h	7.47	0.90	8.18	1.51	.032
3 h	6.53	1.42	6.94	1.01	.279
6 h	4.47	1.48	5.59	0.82	.001
12 h	3.12	1.01	4.06	1.74	.021
24 h	2.76	1.56	3.24	0.99	.305
36 h	1.29	0.97	2.71	1.62	< 0.001

Discussion

According to the current study, group A and group B study participants had mean age of 33.29 ± 8.05 and 31.68 ± 7.58, respectively. The mean age of the research participants was a little bit higher in a study by Kim et al. [16]. According to this study, the participants' average age was 43.35 + 16.32 years. In research conducted by Bernardo et al. [17] participants' average ages were 40.1 ± 13.6 years. In this study, group A had 50% male and 50% female study participants. In group B, there were 55.9% female participants and 44.1% male participants. The group's gender distribution did not differ significantly. 75% of the participants in a study by Kang et al. [18] were men. In research by Kim et al. [16], it was shown that there was no statistically significant difference between the groups.

The mean BMI of the individuals in the current study was 24.21 ± 1.52 and 24.37 ± 1.45 in groups A and B, respectively. There was no difference in BMI between groups that was statistically significant. A similar statistical difference in BMI across the groups was found in research by Kim et al. [19]. Nasal packs soaked with lidocaine have been successfully used to relieve pain in the past. Fentanyl, a fast-acting synthetic opioid with costs comparable to lidocaine, has a pharmacokinetic profile that is more suited for the rapid relief of acute episodic pain [20] It has been demonstrated that intranasal fentanyl has kinetic and dynamic properties that make it perfect for treating acute, episodic pain following nasal surgery [21]. Low plasma concentration, little first-pass effects, and great patient tolerance are all advantages of topical fentanyl pain treatment for the nose. There aren't many systemic side effects either [22]. This is so because fentanyl has more analgesic effects than general analgesia on the ethmoid nerve and maxillary nerve in tissues near the nose [23]. Intranasal fentanyl is widely recognised to provide an analgesic effect equivalent to that of intravenous fentanyl but does not affect vital signs like heart rate or blood pressure or cause respiratory depression [14].

Fentanyl administered intranasally has also demonstrated a rapid onset of analgesic action when used for premedication in children, postoperative pain, acute pain in emergency rooms, procedural wound care pain, and cancer-related breakthrough pain [8]. A highly lipophilic opioid called fentanyl has been investigated for use as an intranasal painkiller. It is a useful delivery strategy that is effective for a variety of opioids [20]. Because fentanyl is lipophilic, it can be given topically via the mucosa to the target area at a lower dosage than intravenously, with less side effects and a longer time to work for pain relief [13]. Fentanyl injected intravenously has a half-life of 3 h, but fentanyl supplied subcutaneously has a terminal half-life of more than 10 h. Only Instanyl and intranasal fentanyl aqueous-buffered solution (fentanyl citrate dose 5, 2, or 1 mcg/mL) are currently approved nasal fentanyl drugs. According to the Royal Children's Hospital in Melbourne, intranasal fentanyl has been used to treat acute nasal pain related to fracture, dislocation, burns, and severe lacerations at a dose of 0.75–1.5 mcg/kg [21]. However, little research has been done on the effects of opioid or fentanyl usage on the mucosa after nasal surgery.

According to the results of the current study, the mean RSS score of group A was 2.03 ± 0.83 and group B was 1.38 ± 0.49. Group A had a much higher RSS score than group B. At 1, 3, 6, 12, 24, and 36 h, respectively, the mean verbal pain intensity scale for group A was 4.53 ± 0.51; 3.82 ± 0.83; 3.70 ± 0.70; 2.5 ± 0.51; 1.88 ± 0.84; and 1.38 ± 0.49. At 1, 3, 6, 12, 24, and 36 h, respectively, the mean verbal pain intensity scale for group B was 5.65 ± 0.49, 4.79 ± 0.84, 4.21 ± 0.81, 2.97 ± 0.83, 2.44 ± 0.50, and 1.97 ± 0.90. Verbal pain intensity scale scores in Group A were consistently lower than those in Group B at all times. At 1, 3, 6, 12, 24, and 36 h, respectively, the mean numeric pain rating scale for group A was 7.03 ± 0.80, 5.85 ± 0.89, 4.91 ± 0.75, 4.09 ± 0.87, 2.85 ± 0.82, and 1.91 ± 0.79. At 1, 3, 6, 12, 24, and 36 h in group B, the mean numeric pain rating scale was 7.91 ± 0.62, 7.03 ± 0.80, 5.74 ± 0.83, 5.21 ± 0.84, 3.74 ± 0.86, and 2.50 ± 0.51. The difference between Group A and B on the numeric pain rating scale was noticeable at all times.

At 1, 3, 6, 12, 24, and 36 h in group A, the mean Wong-Baker pain rating scale was 7.47 ± 0.90, 6.53 ± 1.42, 4.47 ± 1.48, 3.12 ± 1.01, 2.76 ± 1.56, and 1.29 ± 0.97, respectively. At 1, 3, 6, 12, 24, and 36 h, respectively, the mean Wong-Baker pain rating scale for group B was 8.18 ± 1.51, 6.94 ± 1.01, 5.59 ± 0.82, 4.06 ± 1.74, 3.24 ± 0.99, and 2.71 ± 1.62. The Wong-Baker pain rating scale was considerably lower in Group A than B at 1, 6, 12, and 36 h. In research conducted by Kim et al. [19] it was demonstrated that the fentanyl group had a lower Numeric pain rating scale score than the control group. One of the few studies examining the fentanyl nasal pack is ours.

However, research on nasal packages containing lidocaine has demonstrated a comparable effect. A prospective, randomised, double-blind controlled investigation that was conducted by Mo et al. in 2013 [22]. Following the surgery, 31 patients received 2% lidocaine-soaked biodegradable synthetic polyurethane foam and 32 control patients received saline-soaked polyurethane foam nasal packing. The lidocaine group demonstrated a decrease in postoperative pain across all postoperative intervals (p- 0.05). Lidocaine reduced postoperative bleeding at 8- and 24-h following surgery. After surgery, group A experienced headaches at a rate of 14.7% and group B experienced sore throats at a rate of 17.6% and 23.5%, respectively. After surgery, there was no discernible difference in the symptoms across the groups. In groups A and B, post-operative IV fentanyl use rates were 23.5% and 29.4%, respectively. Use of IV fentanyl did not differ significantly across the groups. Only 20.6% of those in group A used IV NSAIDs post-op, compared to 38.2% of those in group B.

Despite the advantages of using fentanyl-soaked packing to reduce pain, safety concerns may come up because it has the potential to have serious negative effects including respiratory depression or low blood pressure. Our examination, however, turned up no proof of respiratory depressions. Intravenous fentanyl at a dose of 1–2 mcg/kg is an effective way to manage postoperative pain in the post-anaesthesia care unit. However, this was not the case in our experiment. It is hypothesised that mucosal fentanyl would have fewer systemic side effects than intravenous fentanyl. However, those who are at risk for respiratory depression or low blood pressure must be continuously monitored.

Conclusion

Despite the introduction of new packing materials, patients continue to be in pain and require additional analgesic therapy. Controlling postoperative pain improves patients’ quality of life by decreasing hospitalisations, preventing postoperative pain complications and increasing patient satisfaction. The current study found that nasal packing loaded with fentanyl is effective in alleviating post-operative pain. Furthermore, future studies assessing the efficacy of fentanyl-soaked nasal packing in the treatment of pain and bleeding should include additional control groups using alternative haemostatic approaches.

Funding

No funding was received for conducting this study.

Declarations

Conflict of interest

The authors whose names are listed above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Compliance with Ethical Standards

This study complies with the ethical standards of our institution.

Ethical Approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Human Ethical Committee of the tertiary care teaching hospital, Puducherry.

Informed Consent

Informed consent was obtained from all individual participants included in the study.