Comparative Effects of Flurbiprofen—Lidocaine Spray Versus Lidocaine Spray Alone as Topical Pharyngeal Anesthesia Before Unsedated Upper Gastrointestinal Endoscopy

Abstract

Objectives: Esophagogastroduodenoscopy (EGD) performed with topical pharyngeal anesthesia presents less adverse events and post-procedural impairment associated with sedation. The aim of this study was to evaluate if by combining Flurbiprofen and Lidocaine sprays for topical pharyngeal anesthesia there is an improvement in patient tolerance and endoscopist satisfaction in comparison to using Lidocaine spray alone. Methods: We conducted a single center, double blind, randomized controlled trial designed to compare unsedated EGD using topical Flurbiprofen spray (Strepsils Intensive^®) plus Lidocaine spray versus Lidocaine spray alone. We assessed patients’ tolerance and endoscopist satisfaction through a 0 to 10 points visual numerical rating scale. Results: A total of 36 patients were included and randomized in two equal groups: Lidocaine and Flurbiprofen spray group (FL) and Lidocaine spray group (L). No significant differences were found amongst groups for patient discomfort score (FL 5.33 ± 2.42, L 5.56 ± 2.12, p = 0.708), pain score (FL 1.77 ± 2.17, L 1.89 ± 0.74, p = 0.119), gag reflex intensity score (FL 1.61 ± 0.82, L 1.83 ± 0.68, p = 0.418), patient satisfaction score (FL 7.78 ± 2.46, L 7.22 ± 1.78, p = 0.428), and endoscopist satisfaction score (FL 7.5 ± 2.87, L 7.58 ± 1.45, p = 0.312). Conclusions: During unsedated EGD, both Lidocaine plus Strepsils spray and Lidocaine spray alone were safe and well tolerated. The combination of Flurbiprofen and Lidocaine did not significantly improve patients’ level of discomfort, pain, gag reflex, and satisfaction and endoscopist satisfaction.

1. Introduction

Upper gastrointestinal endoscopy is a minimally invasive procedure. Since the endoscope tube must be inserted through the mouth, it may cause heightened anxiety, discomfort, coughing and gagging, and an overall significantly unpleasant experience.

The utility of EGD is increasing, and with growing demand, there is a need to ensure quality standards, including patient satisfaction [1].

Endoscopic procedures may be performed with some form of sedation. This allows a thorough and relaxed procedure, with higher pathology detection and procedure completion rates. A sedated, comfortable patient is associated with a higher likelihood of willingness to repeat it and enhanced endoscopist satisfaction [2]. The level of sedation needed depends on the amount of pain the patient is likely to experience, and the necessity of the patient remaining still during the procedure [3]

However, non-sedated EGD also offers several advantages. There is virtually no post-procedural impairment and it avoids the cardiopulmonary adverse events associated with intravenous sedation. Also, it has considerably wider availability [4].

Topical pharyngeal anesthesia with Lidocaine has improved non-sedated EGD tolerance. It facilitates smooth insertion of the endoscope, reduces discomfort, gag reflex, and the risk of injuring of the pharyngeal mucosa, and it also increases endoscopist satisfaction [5,6]. One of Lidocaine’s disadvantages is the risk of methemoglobinemia, a rare adverse reaction. Drug-induced methemoglobinemia has been seen in patients undergoing endoscopic procedures such as EGDs, laryngoscopies, and bronchoscopies. It should be considered in patients presenting with cyanosis and hypoxemia following topical pharyngeal anesthetic use. Despite the rare incidence (0.005% for EGD) [7], most cases of topical-anesthesia-induced methemoglobinemia are secondary to benzocaine, not commonly used in EGD local anesthesia. Benzocaine is a more powerful oxidizing agent compared to Lidocaine, and a dose–response relationship has been observed between benzocaine and methemoglobin [8].

Flurbiprofen (the main substance found in Strepsils Intensive^® (Reckitt Benckiser, Slough, United Kingdom). with honey and lemon spray) is a non-steroidal anti-inflammatory drug (NSAID) with proven analgesic and anti-inflammatory effects. It has also been proven to provide early onset and long-lasting symptomatic relief from throat pain and soreness, sensation of swollen throat, and other associated symptoms that may appear after EGD [9,10].

Numerous studies have compared topical Lidocaine spray to other forms of administration, such as viscous gel, lozenges, lollipops, and nebulized Lidocaine administration. A meta-analysis of seven randomized controlled trials on 2667 participants of Lidocaine spray versus Lidocaine viscous solution for pharyngeal local anesthesia in EGD has shown that the patients’ pain and discomfort were similar among groups, whereas the patients’ satisfaction were higher for Lidocaine spray (relative risk 1.22, 95% CI 1.02–1.47) [11].

Patient’s discomfort can be evaluated using a numeric rating scale (NRS). NRS is a pain screening tool, commonly used to assess pain severity at that moment in time using a 0–10 scale, with zero meaning “no pain” and 10 meaning “the worst pain imaginable” [12].

However, it is still unclear which technique is optimal in terms of its influence on the gag reflex, patient tolerability, and pain [13].

The primary aim of this study is to assess whether Strepsils Intensive^® Honey and Lemon Spray (containing 8.75 mg of Flurbiprofen), when used alongside traditional Lidocaine spray for pharyngeal anesthesia, enhances patient satisfaction and increases the endoscopist’s comfort during upper gastrointestinal endoscopy.

2. Materials and Methods

We have designed a single center, double-blind randomized trial to compare unsedated EGD with topical pharyngeal anesthesia with Lidocaine spray versus topical Flurbiprofen spray (Strepsils Intensive^®) plus topical Lidocaine spray.

We enrolled consecutive patients (either hospitalized or outpatients), with ages above 18 years old, with the indication for unsedated diagnostic EGD, who were referred at “Prof Dr. Agrippa Ionescu Hospital”. The indications of diagnostic endoscopy were symptoms such as dysphagia, dyspepsia, reflux, abdominal pain, or iron deficiency anemia, as well as screening in asymptomatic patients with positive family history for gastric cancer. Patients with previous surgery on the upper aerodigestive tract (partial or total gastrectomy), corrosive substances ingestion, acute gastrointestinal bleeding, pregnancy, or patients with known allergies to lidocaine or flurbiprofen, were excluded. We performed EGD using Olympus EVIS EXERA III GIF–H180 (Olympus Medical Systems Corp, Tokyo, Japan). The endoscopic examination did not routinely involve oxygen supplementation at our endoscopy center.

A fasting period of 8 h before the procedure for solid food, and 2 h for water or other liquid ingestion was required. Included individuals were randomly allocated to one of two groups: Lidocaine spray—Group 1 (4.6 mg per dose, 50 mL vial) or Lidocaine + Flurbiprofen spray (Strepsils Intensive^® 8.75 mg per dose—2 puffs, 15 mL vial)—Group 2. The randomization was carried out using random.org website.

Before procedure, demographic data was recorded for each participant, history of previous EGD, indication for current EGD, biopsy sampling, procedure duration, and anxiety score. Anxiety score was rated on a points scale (0–4). Additional data regarding age, sex, height, weight, age, smoking, alcohol consumption, provenience from rural or urban environment, underlying medical conditions, chronic medication, and family history have been collected. Structured interviews were carried out to assess comfort according to patients, and satisfaction and quality according to endoscopist.

In both groups, two applications of Lidocaine spray (5 puffs each for each application, in total 10 puffs) were applied 5 min before EGD. In addition, in Group 2, Strepsils Intensive^® (2 puffs of 8.75 mg, total of 17.5 mg) were applied 10 min before the endoscopy. EGD was performed by a single operator, blinded to the groups’ allocation.

We hypothesized that the adjunction of Flurbiprofen spray increases the patients’ satisfaction score of topical Lidocaine spray for unsedated EGD by 30%.

After completing the endoscopic examination, a visual analog numeric scale (0 to 10) was used to assess patient satisfaction, discomfort, and pain during procedure, as well as endoscopist satisfaction. Before applying the topical pharyngeal anesthesia, patient anxiety was evaluated using a 0 to 5 numerical rating scale (0, calm to 5, anxious). Patients’ gag reflexes were evaluated at the end of the procedure on a 0 to 4 numerical scale (0, no gag reflex; 1, mild gag reflex; 2, moderate gag reflex; 3, strong gag reflex; 4, strong gag reflex or refused procedure).

Variables were imputed into and analyzed using SPSS 25.0 software (IBM, Endicott, NY, USA). Qualitative variables were expressed as absolute values and percentages, and their comparative analysis among the two groups was performed using Fisher’s exact test. For quantitative and scale variables, Kolmogorov—Smirnov test was performed to determine normal distribution. Mean and standard deviation were used for normally distributed quantitative and scale variables, as well as median and range, for data not normally distributed. For comparison between the two study groups, Student’s T test was used for normally distributed data and Mann–Whitney U test for data not normally distributed. p-value < 0.05 was considered statistically significant. To increase satisfaction score by 30%, with an alpha probability of error of 5% and a power of 80%, we calculated a sample size of 18 patients in each group, with a distribution of 1:1.

Written informed consent was obtained from each patient before randomization. The study was conducted with the Hospital Ethical Committee approval number 807570 from 15th of December 2023 and was listed in Clinical Trials database (NCT06220175), the CONSORT 2025 Flow Diagram as presented in Supplementary Figure S1 [14].

3. Results

From March 2024 to August 2024, a total of 37 patients referred for unsedated EGD at “Prof. Dr. Agrippa Ionescu” Hospital, were evaluated for study inclusion. Out of 37 evaluated patients, one was excluded after refusing to sign informed consent. The remaining 36 patients were included and randomized into 2 groups, 18 in each group. The characteristics of the patients compared between the two types of topic pharyngeal anesthesia received are presented in

Table 1. Patients’ characteristics comparison between the two groups. SD, standard deviation; FL, Lidocaine and Flurbiprofen spray group; L, Lidocaine spray group.

Patient Characteristics Comparison of the Two Groups	FL Group 18 Patients	L Group 18 Patients	p-Value
Age (years) (mean ± SD)	52.11 ± 12.09	58.33 ± 15.57	0.190
Female sex (n, percentage)	9 (50.0)	9 (50.0)	1.000
Weight (kg) (mean ± SD)	73.55 ± 18.45	85.38 ± 26.93	0.135
Smoking (n, percentage)	4 (22.22)	3 (16.6)	1.000
Urban environment (n, percentage)	5 (27.77)	15 (83.33)	0.020
Alcohol intake (n, percentage)	9 (50)	7 (38.88)	0.738
Previous EGD history (n, percentage)	12 (66.67)	12 (66.67)	1.000
Anxiety score (median, range)	2 [0–4]	2 [0–3]	0.887
Biopsy performed during EGD	16 (88.89%)	15 (83.33%)	1.000
Procedure duration, minutes:seconds (mean ± SD)	5:23 min	5:22 min	0.962

.

There were no significant differences in demographic parameters among the two groups, with the exception of environmental provenience (with more patients from the urban environment being included in the Strepsils plus Lidocaine group, while in the Lidocaine group, most patients had a rural provenience).

The mean duration of the procedure was comparable between the two groups (p = 0.962).

The main clinical indication for EGD was dyspepsia in both groups (p = 0.330).

Table 2. Indication for EGD.

Indications for EGD	FL Group	L Group	p Value
Dyspepsia, (n, percentage)	7 (39)	10 (56)	0.330
Anemia, (n, percentage)	0 (0)	2 (11)	0.163
Cancer screening, (n, percentage)	2 (11)	1 (6)	0.560
Others, (n, percentage)	2 (11)	0 (0)	0.163
Screening for esophageal varices, (n, percentage)	2 (11)	3 (17)	0.641
Follow-up, (n, percentage)	3 (17)	2 (11)	0.641
Sudden weight loss, (n, percentage)	2 (11)	0 (0)	0.163

.

Post-procedural evaluation parameters demonstrated similar NRS scores.

The median scores for patient satisfaction, discomfort, and pain during procedure, as well as gag reflex and endoscopist satisfaction, were similar between the two groups with no statistically significant difference (Group 1—Lidocaine spray vs. Group 2—Lidocaine + Flurbiprofen spray) (

Table 3. Comparison of the patient and endoscopist scores between the two study groups. Median (range) and patient satisfaction mean ± SD were also reported.

Comparison of the Patient and Endoscopist Scores Between the Two Study Groups	FL Group	L Group	p-Value
Patient discomfort score during the procedure (0–10) Median (range) Mean ± SD	5.5 [1–10] 5.33 ± 2.42	6 [2–8] 5.56 ± 2.12	0.708
Pain score during the procedure (0–10) Median (range) Mean ± SD	1 [0–10] 1.77 ± 2.17	2 [1–3] 1.89 ± 0.74	0.119
Patient satisfaction score after the procedure (0–10) Median (range) Mean ± SD	9 [1–10] 7.78 ± 2.46	8 [4–10] 7.22 ± 1.78	0.428
Intensity of the gag reflex during the procedure (0–3) Median (range) Mean ± SD	1.5 [0–3] 1.61 ± 0.82	2 [1–3] 1.83 ± 0.68	0.418
Endoscopist satisfaction score during the procedure (0–10) Median (range) Mean ± SD	8 [0–10] 7.5 ± 2.87	7 [5–10] 7.58 ± 1.45	0.312

). Only one participant who had received the Lidocaine spray + Flurbiprofen topical anesthesia could not tolerate the procedure.

4. Discussion

Upper gastrointestinal (GI) endoscopy is a procedure widely used in medical practice, guided by patient comfort and safety. Even though intravenous anesthesia is an option for EGD, it presents the risk of adverse events such as bradycardia, hypotension, and respiratory depression, and requires the presence of an anesthesiologist on the premise. The use of topical pharyngeal anesthesia reduces the risks associated with intravenous sedation. Many studies report the use of different local anesthetic preparations such as viscous Lidocaine solution [11], lozenges [9], ice popsicles [13], and nebulized Lidocaine [11], but the efficacy of these methods are still under debate. In this study, we compared the use of a commercially available Strepsils Intensive Spray in addition to Lidocaine with simple Lidocaine spray in unsedated EGD to measure patients’ satisfaction as the primary outcome. Moreover, we chose to include the endoscopists’ satisfaction as a parameter since the study design included an endoscopic procedure performed by a single blinded operator with an overview of the overall procedure, evaluated using NRS.

Up to date, no data from the literature shows a correlation between the patient environment and endoscopy tolerance [15]. The only predictive factor that showed a significant difference between the two groups included in our study, has been the environmental provenience (rural versus urban provenience). The rest of the predictive factors analyzed show no difference between the two groups compared.

Mahawongkajit et al. have evaluated mean patient satisfaction score from 0 (worst) to 10 with a mean satisfaction score of 8.08 ± 0.82 (using Lidocaine ice popsicles). Their study showed a slight increase in patient satisfaction compared to a mean score of 7.74 ± 0.82, with a median of 8 [2–10] computed in the Lidocaine topical sedation group (with a 5% increase in patient satisfaction score, proven statistically significant). Compared to spray preparations, the Lidocaine ice popsicle preparation was superior in terms of reducing the gag reflex, improving patient satisfaction, discomfort, and pain. The ice popsicle melted slowly and may have increased the exposure to Lidocaine on the pharyngeal mucosa [13]. Our study demonstrated mean patient satisfaction score of 7.78 ± 2.46, from 0 (worst) to 10 (best), with a median of 9 [0–10] in the Lidocaine plus Strepsils topical sedation, compared to a mean score of 7.22 ± 1.78 with a median of 8 [4–10] computed in the Lidocaine topical sedation group, thus presenting an 8% increase in patient satisfaction score, though not proven statistically significant.

When comparing 30 and 100 mg Lidocaine spray in unsedated EGD, Mulcahy et al. proved that higher drug doses are associated with better results [16]. However, no direct comparison between Flurbiprofen 20 mg in addition to Lidocaine 100 mg as a topical anesthesia was performed in the past. As seen in our study, the slight superiority of Flurbiprofen used in addition to the classic Lidocaine spray may be attributed to the difference in total dosage (an additional 20 mg of flurbiprofen being administered to the 100 mg of Lidocaine). The efficacy of topical anesthesia is presumably related to the dosage of anesthetic used. We also proposed that a Lidocaine plus Strepsils double-spray sedation could reduce the pre-procedural patient anxiety score before EGD. Nonetheless, we found the scores to be similar (with a slightly higher mean anxiety score for the Strepsils plus Lidocaine spray topical pharyngeal sedation). Similar findings have been computed before by prospective publications about the relationship between patient knowledge and anxiety levels [15]. A recent study carried out at Tanta University Hospital showed that high pre-procedural levels of anxiety were associated with a low patient tolerance [17]. Possible factors that could lead to a patient’s anxiety before upper gastrointestinal (GI) endoscopy procedure are fear of injury and choking, discomfort, and unexpected diagnoses such as cancer. Previous articles have stated that female patients had higher levels of pre-procedural anxiety and poor tolerance of endoscopy. Also, lean patients are more irritable and hyperactive during endoscopy. Older patients have been found to exhibit lower anxiety levels and better tolerance during endoscopy [18].

Pre-procedural anxiety and fear of feeling discomfort and pain can act in concert, aggravating the effect of each factor separately, and finally lead to intolerance of the endoscopic procedure and poor-quality endoscopy [18]. Providing adequate information before upper GI endoscopy can lead to diminished anxiety, fear, and worry in the patients during the procedure [15]. We also observed in our study that patients with a history of previous EGD had a lower anxiety score (Mean = 1.45) as compared to patients with no previous EGD (Mean = 2.25). No studies that we know of, approaching this subject, have been published until this date.

Ayoub et al. have proven that the most uncomfortable part of EGD, as graded by the patients, is esophageal intubation [19]. Topical pharyngeal anesthesia is ineffective in controlling the discomfort created by the passage of the scope through the cricopharyngeal junction. Use of an ultrathin endoscope reduces the distension of the cricopharyngeus—the diameter of the ultra-thin endoscope being 5.9 mm as compared to the 9.8 mm instrument used in the standard EGD—and has been found to be more tolerable than conventional EGD amongst unsedated patients. A randomized trial by Murata et al. showed that the ultra-thin endoscope is more tolerable than conventional EGD with unsedated patients (though, in the case of transnasal EGD, examinations can encounter certain difficulties due to anatomical reasons such as septum deviation and chronic rhinitis). The drawback of the ultra-thin endoscope is the smaller endoscopic view compared with conventional EGD, which may make the examination technically demanding. Moreover, the biopsy samples are smaller in size and therapeutic procedures are also limited by the small working channel with the ultra-thin endoscope [20].

The importance of this study comes from the extremely limited data in the field, this being a strength. Moreover, the study is a prospective, double-blind, randomized study, adding value to the data. There are several limitations such as the small number of patients limiting the statistical power. This study does not take into consideration other potential factors that could influence the tolerance during the procedure (such as additional underlying medical conditions and chronic medication taken by the patient).

5. Conclusions

We have concluded that both Lidocaine and Lidocaine + Strepsils spray preparations were safe and effective in producing local anesthesia and were well tolerated by patients. This study shows no statistically significant difference between Lidocaine versus Lidocaine plus Flurbiprofen topical pharyngeal anesthesia in regard to patient comfort, gag reflex, or endoscopist satisfaction score. Larger randomized controlled trials would be useful to enhance the validity of the results.