This was the first study using benzydamine hydrochloride mouthwash prior to ERCP procedure. The results showed that cumulative propofol requirements in the benzydamine hydrochloride group was significantly less than in the control group. The result is consistent with other studies using topical anaesthetics in endoscopic procedures conducted by Soweid et al. (2011) and Basturk et al. (2017) which used lidocaine in the form of spray or gel [3, 5]. However, lidocaine spray might cause irritation, nausea, vomiting, and dysphagia. Thus, it was not commonly used and benzydamine hydrochloride mouthwash became an alternative for this approach.
Benzydamine hydrochloride has been used in years to reduce the mucosal inflammation due to radiotherapy radiation and to reduce the incidence of sore throat postprocedure in patients undergoing general anaesthesia with endotracheal intubation or laryngeal mask airway devices [7, 8]. The agent was used as a mouthwash before the procedure began. Gargling is effective in distributing the agent into oropharyngeal area, posterior pharyngeal wall, anterior epiglottis area, and uvula [8, 9]. Thus, those areas would be covered by the agent and it reduced the sore throat in patients undergoing the procedure.
Sore throats are usually complained after the procedure due to inflammation on the mucosa. This inflammation will improve after some time, as the literature says it will improve in the first 24–72 h postoperatively . However, this study found that pain caused by sore throat could be reduced until 4 h postsedation with the use of benzydamine hydrochloride mouthwash before the procedure. The agent might give topical anaesthesia effect until 90 min after administration. Moreover, the complaint of sore throat was significantly reduced due to anti-inflammatory effect from the agent.
Benzydamine hydrochloride has several common features to other nonsteroidal anti-inflammatory drugs (NSAIDs) such as analgesia effect and anti-inflammatory effect. The local analgesia effect worked only on localized inflammatory factors without any interaction to systemic mechanism . Moreover, the anti-inflammatory effect might occur due to its ability in modulating the transformation of blood vessels and in suppressing the work of phagocytic cells. Therefore, the occurrence of vasodilation and the increase of vascular permeability would be prevented while the release of granules and lytic enzymes would be reduced [9, 11].
The agent is recommended to be given about 4 mmol/L in 15 mL and gargled for 30 s. The agent should be administered in high concentration because only small amount of this agent would work effectively while the rest of it would be dissolved in saliva. The diffusion depth of topical administration is not exactly understood. However, some studies stated that most of it would be more concentrated in the tissue surface compared to when administered systemically [8, 9]. The local anesthesia effect of benzydamine hydrochloride might be the cause of significant decrease of cumulative propofol consumption in this study.
At concentration of 10–100 μmol/L, benzydamine hydrochloride may stabilize the mucosal membrane whereas at concentration of 3–30 μmol/L, it might inhibit the release of azurophilic granules from neutrophils. Similar mechanism has been shown by other drugs which have membrane stabilization effects such as beta blockers, local anesthetics, and some NSAIDs with acidic features when given in high doses. In experiment involving fat cells in vitro, benzydamine hydrochloride might increase the formation of cyclic 3′,5′-AMP which affects the activity of intracellular cation. This effect may originate from the activity of local anesthetics held by benzydamine hydrochloride .
In this study, desaturation occurred in the control group while hypotension occurred in both groups. These side effects might be related to propofol usage during the ERCP procedure and were not related to benzydamine hydrochloride. Propofol has been known to induce desaturation, hypotension, apnea, allergic reactions, and cardiac arrest [12, 13]. However, the incidence of desaturation and hypotension was higher in the control group than in benzydamine hydrochloride group. This could be caused by higher cumulative dose for propofol in the control group. Hence, the incidence of hypotension and desaturation will increase in proportion to the increase of propofol dose .
Other minor side effects that can happen during the use of benzydamine hydrochloride are nausea, vomiting, and dysphagia due to numbness in the mouth . In this study, there was no incidence of dysphagia in either control group or the benzydamine hydrochloride group while complaints of nausea and vomiting were comparable in both groups. However, the ERCP procedure itself can also precipitate nausea and vomiting due to contrast used during procedure or pancreatic inflammation, which is a serious complication of this procedure [15, 16]. In addition, the use of fentanyl in ERCP anesthesia procedure may cause nausea and vomiting postprocedure .
The single use of Ramsay Sedation Scale, as an indicator to assess the depth of sedation, was the limitation in this study. This scale might lead to bias because the depth of anesthesia can be more objective if assessed with Bispectral Index (BIS). The use of BIS monitors has been known to provide anesthesiologists in assessing the depth of anesthesia in patients receiving sedation . Furthermore, other possible bias was the taste and appearance of water, compared to benzydamine hydrochloride. In order to maintain blindness for the patient, dark colored container was used and it was discarded into black colored plastic bag. There was no explanation regarding the taste to the patient prior to the procedure. Moreover, there was no contact between each patient from each group before and after the procedure. In this study, endoscopist’s statisfaction towards this method has not been further elaborated. However, this might lead to a subjective satisfaction ratings according to different perspectives.