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INTRODUCTION
Tonsillectomy remains one of the most frequently performed surgical procedures in otorhinolaryngology, with over 600,000 cases annually in the United States alone (Afman et al., 2006). Despite its ubiquity, the procedure is associated with intense postoperative pain that is often reported as more severe than major abdominal or orthopedic surgeries (Gerbershagen et al., 2013). This pain typically peaks between postoperative days three and five, frequently leading to poor oral intake, dehydration, and unplanned readmissions (Geißler et al., 2025; Roskvist et al., 2024).
The pathophysiology of post-tonsillectomy pain involves mechanical trauma to the pharyngeal constrictor muscles and the exposure of raw nerve endings in the tonsillar fossa. This triggers the release of inflammatory mediators that sensitize peripheral nociceptors (Guntinas-Lichius et al., 2023). While systemic multimodal analgesia-including paracetamol, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and intraoperative steroids-is the current standard, it often fails to adequately control breakthrough pain during swallowing (Aldamluji et al., 2021; Geißler et al., 2019). Studies indicate that up to 26% of adult patients contact healthcare providers due to insufficient home pain management (Roskvist et al., 2024).
Topical anesthetics offer a non-invasive, localized alternative to manage breakthrough symptoms. Oxybuprocaine hydrochloride (benoxinate) is an ester-type anesthetic known for its rapid onset and high mucosal permeability. While its efficacy has been explored in pediatric populations using gel (Xiaoning et al., 2023) dose-response evaluation. This study aims to identify the optimal concentration of oxybuprocaine gargle that balances analgesic efficacy with local side effects like oral numbness.
MATERIALS AND METHODS
Ethical Approval
This prospective, randomized pilot study received approval from the Institutional Ethics Committee (No. PJ - Department - 2022 - 155) and adhered to the Declaration of Helsinki. All participants provided written informed consent.
Participants
Sixty adult patients scheduled for bilateral tonsillectomy were recruited. Inclusion criteria included: (1) ASA grade I-II; (2) Age 18-60 years; and (3) No history of chronic pain syndromes or neurocognitive deficits (Wong Chung et al., 2018). Patients with a history of recurrent peritonsillar abscess or allergies to local anesthetics were excluded (Caixeta et al., 2020).
Surgical Procedure
All procedures were performed under general anesthesia using low-temperature plasma (Coblation) technology. Coblation is associated with reduced thermal damage to surrounding tissues and lower primary hemorrhage rates compared to electrocautery.
Intervention and Randomization
Patients were randomized (1:1:1:1) into four groups (n=15 each):
- Control: 0.9% NaCl (Saline).
- Group A: 0.3% Oxybuprocaine hydrochloride solution.
- Group B: 0.15% Oxybuprocaine hydrochloride solution.
- Group C: 0.06% Oxybuprocaine hydrochloride solution.
Patients gargled 10-15 mL of the assigned solution for 30 sec, three times daily from postoperative day 1 to 3.
Outcome Measures
The primary endpoint was pain reduction, calculated as the difference between pre-gargling VAS scores and scores 10 min post-administration. Secondary outcomes included the incidence of adverse reactions such as tongue numbness, nausea, or bleeding.
Sample Size Justification
As a pilot feasibility study, the sample size of 15 patients per arm was chosen to provide preliminary estimates of variability and effect size. This aligns with statistical "rules of thumb" for exploratory clinical trials, which suggest 12-15 participants per group are sufficient to power future definitive trials (Whitehead et al., 2016).
RESULTS
Sixty patients completed the study. There were no significant differences in age, sex, smoking status, or operation time across the four groups (p>0.05). The mean age was 34.50±11.00 years, with a baseline surgical time of 29.20±9.95 min (Table 1).
| Variable | Control (n=15) | Group A (0.3%) | Group B (0.15%) | Group C (0.06%) | p-value |
|---|---|---|---|---|---|
| Age (years) | 37.00±13.73 | 32.80±9.63 | 36.40±10.26 | 31.80±10.11 | 0.488 |
| Sex (M/F) | 11 / 4 | 8 / 7 | 7 / 8 | 9 / 6 | 0.494 |
| Surgery Time (min) | 33.53±12.50 | 27.53±12.00 | 28.93±7.82 | 26.80±5.13 | 0.249 |
Analgesic Efficacy
VAS reduction was significantly higher in Group A (2.71±1.17) and Group B (1.08±0.71) compared to the Control group (0.06±0.12, p<0.001). Group C (0.50±0.44) showed a minor trend toward relief but did not reach statistical significance compared to the control (p=0.101). Pairwise comparison showed Group A provided significantly greater relief than all other groups (p<0.05) (Table 2).
| Group | VAS Reduction (Mean±SD) | Adverse Reactions n (%) | p-value (vs. Control) |
|---|---|---|---|
| Control | 0.06±0.12 | 0 (0.0%) | - |
| Group A (0.3%) | 2.71±1.17 | 8 (53.3%) | <0.001 |
| Group B (0.15%) | 1.08±0.71 | 5 (33.3%) | <0.001 |
| Group C (0.06%) | 0.50±0.44 | 3 (20.0%) | 0.101 |
Safety Profile
Adverse reactions were reported by 26.7% of the total cohort, all of which were mild and self-limiting. The incidence followed a clear dose-response curve: 53.3% in Group A, 33.3% in Group B, and 20.0% in Group C (p=0.005). The most common symptoms were transient tongue numbness and mild nausea. No serious complications, such as secondary hemorrhage or systemic anesthetic toxicity, were observed (Table 3).
| Comparison Pair | Fisher's Exact (Value) | p-value |
|---|---|---|
| Control vs. Group A | 10.909 | 0.001* |
| Control vs. Group B | 6 | 0.014* |
| Group A vs. Group B | 1.222 | 0.269 |
| Group B vs. Group C | 0.682 | 0.409 |
DISCUSSION
Managing post-tonsillectomy pain remains a significant challenge, with standard multimodal care often falling short during the critical 72-hr period after discharge (Alm et al., 2021). The analgesic effect is likely mediated by the rapid blockade of sodium channels in the exposed nerve endings of the tonsillar bed. Unlike systemic opioids, which act centrally, topical anesthetics target the circulus tonsillaris plexus directly, dampening the primary source of nociception. Previous studies have indicated that topical lidocaine spray can reduce pain until the third postoperative day, but oxybuprocaine’s higher mucosal permeability may provide a more robust effect in the denuded surgical site. Our results demonstrate that topical oxybuprocaine gargle provides immediate, clinically meaningful relief for breakthrough swallowing pain by directly targeting the sensitized nerve endings in the tonsillar fossa (Grainger and Saravanappa, 2008), providing a non-invasive tool for patients to manage their symptoms at home.
The strong dose-response relationship observed suggests that a threshold concentration is required to penetrate the surgical slough and reach the deeper nociceptors. While 0.3% oxybuprocaine (Group A) achieved the highest pain reduction, its high rate of tongue numbness (over 50%) is a major drawback. Excessive oral numbness in a surgical patient can cause anxiety and theoretically increase the risk of aspiration or tongue biting during meals (Hung et al., 2010).
Group B (0.15%) appears to be the most practical choice for clinical integration. It maintained a statistically significant VAS reduction (1.08 points) while keeping adverse reactions at a manageable level (33.3%). In the context of multimodal therapy, even a 1-point reduction on the VAS is considered clinically significant, particularly when it addresses the patient's primary trigger for pain-swallowing (Geißler et al., 2019; Guntinas-Lichius et al., 2023).
While invasive peritonsillar infiltration with agents like levobupivacaine provides excellent intraoperative and early (24 hr) relief (Abo Elfadl et al., 2022; Kasapoglu et al., 2013), its effect wanes quickly. Non-invasive gargles provide patients with a "rescue" tool they can self-administer at home during peak pain periods (Geißler et al., 2025; Ugur et al., 2013). This could reduce the reliance on rescue opioids, which are associated with significant side effects like nausea and constipation (Aldamluji et al., 2021). Furthermore, by effectively controlling acute pain on the first postoperative day, this intervention may help prevent the development of chronic postsurgical pain syndromes.
This study has several limitations inherent to its pilot design. The sample size (n=60) is sufficient for exploratory purposes but lacks the power to detect subtle differences in recovery metrics like time to resume a normal diet or secondary hemorrhage rates. Additionally, the lack of a double-blind design may have introduced reporting bias. Future large-scale, multi-center Randomized Controlled Trials (RCTs) should employ blinded assessments and extend follow-up to evaluate long-term functional outcomes and quality of life (Geißler et al., 2025).
CONCLUSION
Topical gargling with 0.15% Oxybuprocaine hydrochloride is a feasible, safe, and effective adjunct for managing adult post-tonsillectomy pain. It effectively bridges the gap between systemic analgesia and breakthrough swallowing pain.