Benzydamine Hydrochloride and Post-operative Sore Throat (DIFFLAM)

The Effect of Benzydamine Hydrochloride Spray on Post-operative Sore Throat: a Randomized Controlled Study

Postoperative sore throat (POST) after laryngeal mask airway (LMA) insertion is prevalent and unappealing. A significant cause of POST is mechanical injury to the airway mucosa during airway instrumentation, leading to mucosal injury and inflammation. The Difflam Forte Anti-Inflammatory Throat Spray (Difflam) contains benzydamine hydrochloride, a non-steroidal anti-inflammatory agent with topical analgesic properties. This study will randomize 106 women undergoing gynaecological surgery under general anaesthesia with LMA use at KK Women's and Children's Hospital (KKH) in 1:1 allocation ratio of study (Difflam spray) and control (usual practice; no intervention) groups. Demographic and intraoperative airway data collection will be conducted in perioperative period. Those allocated to study group will receive Difflam spray when awake in the post-anaesthesia care unit (PACU). The primary aim to determine if patients undergoing general anaesthesia with LMA use with the Difflam spray in PACU will have a lower incidence of POST in the immediate and 4 hours postoperative recovery period, as compared with those in the control group. Other outcome measures include the severity of pain of sore throat as measured by the visual analog scale, and incidence of side effects associated with the Difflam spray. This proposal will determine whether the use of Difflam spray is suitable to be implemented in local clinical setting and improve perioperative care.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Care; Sore Throat
• Intervention / Treatment: Drug: Benzydamine Hydrochloride

Detailed Description

Postoperative sore throat (POST) after laryngeal mask airway (LMA) insertion is common, with reported incidences being as high as 40 - 60%. This is in spite of ongoing efforts to address this pertinent issue, including utilization of updated iterations of LMA devices, reduction of LMA cuff pressure, etc.. POST is an independent predictor of patient dissatisfaction following general anaesthesia and should be investigated further.

The cause of POST is multifactorial, with various mechanisms at play. A significant cause of POST is mechanical injury to the airway mucosa during airway instrumentation, leading to mucosal injury and inflammation. While the application of topical lidocaine on airway mucosa after surgery for analgesic relief may seem to be a possible solution, this may however, increase the risk of aspiration due to diminished cough reflex and swallowing ability. On the other hand, mouth gargles with analgesics may not provide immediate relief for POST as they require much cooperation from the patient that proves to be challenging in the immediate postoperative period.

The Difflam Forte Anti-Inflammatory Throat Spray is an over-the-counter medication indicated for temporary relief of painful mouth and throat conditions. It contains benzydamine hydrochloride (BH) 3 mg/mL, a non-steroidal anti-inflammatory agent (NSAID), and is recommended for adults to spray 2 to 4 times to the affected throat every 1.5 to 3 hours as needed. The effectiveness of benzydramine on alleviating sore throat has been well established in modern medicine. However, a spray formulation of this medication has not been utilized for this purpose yet. With the spray formulation, patient cooperation will not be required for effective delivery of BH medication - a critical factor in view of patient drowsiness post operation.

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • KK Women's and Children's Hospital
    • Contact: Ban Leong Sng; Phone Number: 65 6394 8436; Email: sng.ban.leong@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. American Society of Anaesthesiologists (ASA) physical status 1-2
2. Female patients having laryngeal mask airway (LMA) for airway management for surgery in KKH;
3. BMI < 40 kg/m2.

Exclusion Criteria:

1. Pregnant;
2. Pre-existing sore throat, or history of upper respiratory tract infection/ abnormalities, hypertension, chronic pain or anti-inflammatory drugs and antihypertensive treatment;
3. Allergies to benzydamine hydrochloride;
4. Symptomatic hiatus hernia;
5. Severe gastroesophageal reflux disease;
6. Contraindications to the use of LMA.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Study group will receive Difflam spray by delivering 4 sprays to the posterior pharynx. Patients will be asked to swallow after each spray. Questionnaires will then be administered to the patients 10 minutes after administration of the intervention, and then 4 hours after for their pain scores and side effects, if any.	Drug: Benzydamine Hydrochloride; The Difflam Forte Anti-Inflammatory Throat Spray (iNova Pharmaceuticals Pte Ltd, Singapore) is an over-the-counter medication indicated for temporary relief of painful mouth and throat conditions. It contains benzydamine hydrochloride (BH) 3 mg/mL, a non-steroidal anti-inflammatory agent (NSAID), and is recommended for adults to spray 2 to 4 times to the affected throat every 1.5 to 3 hours as needed.; Other Names: benzydamine hydrochloride 3 mg/mL; Difflam Forte Anti-Inflammatory Throat Spray
No Intervention: Control group; Patients will be asked to fill in questionnaires for their pain scores and side effects, if any.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative sore throat	Presence of postoperative sore throat (POST) during the immediate and 4 hours postoperative recovery period. At these two time points patients will be asked whether they have sore throat; and answering 'yes' will be considered as 'POST present'.	1 day; from the immediate and 4 hours postoperative recovery period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain score	Pain score during the immediate and 4 hours postoperative recovery period after intervention (Visual analog scale 0-10) will be asked, with zero being no pain, and 10 being the worst pain possible.	1 day; from the immediate and 4 hours postoperative recovery period
Side effects	Presence of side effects during the immediate and 4 hours postoperative recovery period. At these two time points patients will be asked whether they have burning and/or stinging, dry mouth, cough, local numbness; and answering 'yes' will be considered as 'burning and/or stinging, dry mouth, cough, local numbness present'.	1 day; from the immediate and 4 hours postoperative recovery period

Collaborators and Investigators

• Sponsor: KK Women's and Children's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: laryngeal mask airway; Sore throat; benzydamine hydrochloride; Posoperative care
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pharyngeal Diseases; Pharyngitis; Anti-Inflammatory Agents; Benzydamine
• Other Study ID Numbers: 2021/2264

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To be shared upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No