|Year : 2013 | Volume
| Issue : 2 | Page : 52-56
Lidocaine lozenge versus lidocaine spray as topical anesthesia before direct awake laryngoscopy: A randomized active controlled trial
Santosh K Kacker1, B Jagannath2, Sanjay H Maroo3, Ketan R Patel4, Vipul I Prajapati3, Rakesh U Ojha3
1 Delhi ENT Hospital and Research Centre, New Delhi, India
2 Department of ENT, KIMS Hospital, Bengaluru, Karnataka, India
3 Department of medical services, Troikaa Pharmaceuticals Limited, Ahmedabad, India
4 Chairman and Managing Director, Troikaa Pharmaceuticals Limited, India
|Date of Web Publication||7-May-2014|
Vipul I Prajapati
Department of Medical Services, Troikaa Pharmaceuticals Limited, Commerce House 1, Opposite Rajvansh Apartment, Satya Marg, Bodakdev, Ahmedabad - 380 054, Gujarat
Source of Support: Troikaa Pharmaceuticals Limited, Conflict of Interest: The study is sponsored by Troikaa Pharmaceuticals Ltd.
and some of the authors are in the management / payroll of the
Clinical trial registration CTRI/2011/091/000155
| Abstract|| |
Context: Key to successful awake direct laryngoscopy is establishing reliable local anesthesia. Lidocaine spray was reported to be effective in laryngoscopic procedure with less hemodynamic and cardiovascular disturbances. Novel formulation of lidocaine as lozenges was developed to avoid problems of throat irritation and bitter taste associated with spray. Aims: The aim of the following study is to compare the efficacy and safety of lidocaine lozenges versus lidocaine spray in patients undergoing awake diagnostic direct laryngoscopy. Design: A prospective, randomized, open label, active controlled, multicentric study. Subjects and Methods: Patients of either sex, aged between 18 to 80 years and undergoing awake diagnostic direct laryngoscopy were enrolled after screening for eligibility criteria. Enrolled patients were randomized to one of the two treatment; lidocaine lozenges 200 mg and lidocaine spray 200 mg to be applied as a single dose before laryngoscopy. Immediately after the procedure, efficacy, and safety was assessed. Statistical Analysis: Between groups comparison was done using appropriate parametric or nonparametric tests. Results: Investigator experienced significantly lesser procedural difficulty and reduced gag reflex during the procedure with lidocaine lozenges compared to spray. Lesser number of patients experienced aversive symptoms (especially nausea, vomiting, cough, and pain) during and after the procedure and significantly more number of patients preferred to have a repeat procedure with lidocaine lozenges compared to spray. The global assessments by the patient and investigator favored lidocaine lozenges over spray. Conclusion: Lidocaine lozenges given before direct awake laryngoscopy provide a significant benefit by offering a more effective, safe, and convenient anesthesia compared to spray.
Keywords: Laryngoscopy, lidocaine lozenge, lidocaine spray
|How to cite this article:|
Kacker SK, Jagannath B, Maroo SH, Patel KR, Prajapati VI, Ojha RU. Lidocaine lozenge versus lidocaine spray as topical anesthesia before direct awake laryngoscopy: A randomized active controlled trial. J Laryngol Voice 2013;3:52-6
|How to cite this URL:|
Kacker SK, Jagannath B, Maroo SH, Patel KR, Prajapati VI, Ojha RU. Lidocaine lozenge versus lidocaine spray as topical anesthesia before direct awake laryngoscopy: A randomized active controlled trial. J Laryngol Voice [serial online] 2013 [cited 2017 Nov 24];3:52-6. Available from: http://www.laryngologyandvoice.org/text.asp?2013/3/2/52/132047
| Introduction|| |
Direct laryngoscopy is a valuable tool in the examination of laryngeal and supraglottic anatomy and pathology of various conditions.  Laryngoscopy may be accompanied by cardiovascular and hemodynamic disturbances such as tachycardia and hypertension. The key to successful laryngoscopy is establishing reliable local anesthesia. Among all local anesthetics, lidocaine was found to be most effective in attenuating hemodynamic and cardiovascular disturbance. ,
Among available topical formulations, lidocaine spray was found to be an effective method for attenuating pressor response to laryngoscopy and intubation without producing an increased risk of hypotension. However, spray causes throat irritation and leaves a bitter taste in the throat which may be due to additives in the spray formulation. ,
To overcome the limitation of available formulations of lidocaine for local anesthesia, Troikaa Pharmaceuticals Ltd., India has developed lidocaine lozenges on a stick (like a lollipop), a novel method of providing local anesthesia and has been approved in India as a single agent anesthesia for upper gastrointestinal endoscopy.
Literature reported that lidocaine lozenges have been used successfully before the performance of awake tracheal intubation, fiber-optic bronchoscopy and esophagogastroduodenoscopy in adults and also in the elderly patients, patients with comorbidities and office-based endoscopy. ,
Therefore, the present study was designed to compare the efficacy and safety of lozenges versus lidocaine spray in patients undergoing awake direct diagnostic laryngoscopy.
| Subjects and Methods|| |
This randomized, open-label, parallel group, active controlled study was conducted at two study centers in India. A total of 100 patients with suspected laryngeal disorder requiring awake direct diagnostic laryngoscopy were selected.
The study was initiated at each center after getting ethics committee approval from respective study centers followed by registration into a clinical trial registry India (CTRI Reg. No CTRI/2011/091/000155). The patients who required awake direct diagnostic laryngoscopy were explained the procedure and written informed consent was taken before subjecting to the screening process. During informed consent process, each patient was informed that participation in this study is entirely voluntary and they can choose not to take part or can leave the study at any time. After explaining all the study related procedure and other essential information laid down in Annexure V of Schedule Y and Indian Good Clinical Practice, voluntary written informed consent was taken from each patient.
The enrolled patients were identified only by randomization number, not by name or initials during the conduct of study at each study center. Study was conducted as per ethical guidelines for biomedical research on human participants from Indian Council of Medical Research (India), good clinical practice guideline and Schedule Y from Central Drugs Standard Control Organization (India), International Conference on Harmonization guideline for good clinical practice.
Patients of either sex, aged between 18 to 80 years and requiring awake direct diagnostic laryngoscopy with American society of anesthesiologist physical status I or II were eligible for enrolment in the study between March and July, 2011.
During the screening visit, medical history was obtained; Physical examination and laboratory testing were performed. The patients with a medical history of significant impairment of hepatic/renal/cardiac functions and respiratory disease such as asthma, bronchitis or chronic obstructive pulmonary disease were excluded. The patients with history of hypersensitivity to amide type of local anesthetics, emergency surgery or surgery needing hospitalization were also excluded from the study. The women of child bearing age underwent urine pregnancy test; pregnant and lactating women were excluded from this study.
Enrolled patients were randomized into two groups: Group A and B as per computer generated randomization sheet. Patients of Group A received lidocaine lozenges 200 mg (Xynova 200, manufactured by Troikaa Pharmaceuticals Ltd., India) and patients of Group B received lidocaine spray equivalent to 200 mg of lidocaine. Direct awake laryngoscopy procedure was performed by an Otolaryngologist (ear, nose, and throat surgeon).
Single dose of lidocaine lozenge was given 15-20 min prior and lidocaine spray was given 5 min prior to performing awake direct laryngoscopy procedure. Two sprays were given consecutively at an interval of 1 min. Each interval consisted of 10 sprays (10 mg/spray) equivalent to 200 mg of lidocaine. After the procedure was completed, investigator assessed the effectiveness and safety of local anesthesia in both treatment groups.
Immediately after the procedure, investigator filled the questionnaire evaluating (1) ease of laryngoscopy procedure: recorded on an ascending scale from 1 (easy) to 5 (difficult). The criteria used to evaluate the procedural difficulty included the presence of excessive gag reflex, retching, restlessness, and combativeness, (2) Gag reflex level: Gag reflexes were manually assessed if possible after the administration of study drugs at the onset of the procedure and recorded on a scale of 1-5 (1 being strong gag reflex and 5 being absent gag reflex) and (3) ease of administration of local anesthetic. 
After the procedure a blinded member of the study team interviewed the patient and filled a questionnaire evaluating (1) tolerability for the procedure: tolerability of procedure as determined on 0-5 scale where 0 is indicates no difficulty and 5 indicates very difficult, (2) Aversive symptoms experienced during and after the procedure (especially nausea, vomiting, cough, and pain), and (3) the patients were asked whether they would prefer repeating the procedure, if necessary, with the same method of anesthesia or an alternative one. 
Complete monitoring of all the vital parameters were done before and after the procedure. In addition, complete physical (general and systemic) examination of each patient was performed before and after the procedure. Any adverse events observed/reported during the study period were noted in the case record form. At the end of the study, overall efficacy and safety of the study drugs (test and reference) were rated by patients and investigator on a global assessment scale.
The sample size was calculated by assuming primary efficacy endpoint, ease of the procedure. Considering the power of 90% to detect the difference of 0.75 between both treatments, 46 patients will be required in each group based on standard deviation (SD) of 1.1.  Considering a dropout rate of 10%, 102 patients would be required for two groups. For continuous variables, values are expressed as mean ± SD and comparisons between treatments were made using unpaired Student's t-test. Between groups comparison was done using appropriate parametric or nonparametric tests, depending on the type and distribution of data. For categorical outcomes, between groups comparison were performed using Chi-square test or fisher exact test depending upon the size of data. All statistical analyses were performed using "GraphPad prism; version 05"(GraphPad Software, Inc.). P < 0.05 was regarded as "statistical significant difference" between both treatment groups.
| Results|| |
A total of 115 patients were screened and out of that 100 patients were enrolled and successfully completed study without any protocol deviation. Data obtained from all 100 patients were subjected to statistical analysis [Figure 1]. The indication of awake diagnostic direct laryngoscopy included hoarseness of voice, dysphagia, foreign body sensation in the throat and hemoptysis. A brief description of demographic data and type of indication for both the study groups is presented in [Table 1].
The effect of lidocaine lozenges and spray on ease of procedure, level of gag reflex and tolerability of procedure are shown in [Table 2]. The results suggested that the procedure was significantly less difficult (more easier) with the use of lidocaine lozenges as compared to lidocaine spray. In addition, the patients who were treated with lidocaine lozenges experienced statistically significant reduced gag reflex during the procedure when compared with the patients treated with lidocaine spray. However, both study drugs were similar in terms of tolerability of the procedure as there was no statistically significant difference among both the treatment groups.
|Table 2: Effect of lidocaine lozenges and spray on investigator's related parameters|
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The effect of lidocaine lozenges and spray on ease of application of anesthetic agent, symptoms experienced during and/or after the procedure and patient's preference for repetition of procedure with same and alternative anesthetic agents are shown in [Table 3]. The results suggested that the application procedure of lidocaine lozenges was rated easier as compared to lidocaine spray. Significantly lesser number of patients treated with lidocaine lozenges experienced aversive symptoms (especially nausea, vomiting, cough, and pain) during and after the procedure as compared to patients who received lidocaine spray. In addition, the results suggested that significantly more number of patients preferred to have a repeat procedure with lidocaine lozenge as compared to patients who received lidocaine spray.
|Table 3: Effect of lidocaine lozenges and spray on patient's related parameters|
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No case of any abnormality in the vital data as well as in physical examination was found after procedure. No cases of any expected and unexpected adverse events were reported/observed during the study period.
The global assessments of the patient and Investigator in terms of overall efficacy and safety of lidocaine lozenges and spray is shown in [Table 4]. Statistical analysis suggested that patients and Investigator's global assessment scores was significantly more favorable toward lidocaine lozenge than lidocaine spray.
| Discussion|| |
Lidocaine has well-established efficacy and safety as a local anesthetic for laryngoscopy procedure. Among different available formulations, topical lidocaine spray was found to be effective in attenuating pressor response to laryngoscopy and intubation without producing an increased risk of hypotension. However, it causes throat irritation and leaves a bitter taste in the throat, which is reported to be due to additives in spray formulation. , Lidocaine lozenge on a stick (like a lollipop) is a novel method of providing local oropharyngeal anesthesia. This has been developed and evaluated in patients planned for awake direct diagnostic laryngoscopy in multicenter, randomized, single dose, parallel, comparative, active controlled study.
The results of the study demonstrated that both lozenge and spray formulation of lidocaine is safe and effective for the patients scheduled for awake direct diagnostic laryngoscopy. However, the investigator experienced lesser procedural difficulty and observed reduced gag reflex during the procedure with the use of lidocaine lozenges as compared to lidocaine spray. Similar results of lidocaine lozenges over spray were also reported by Ayoub et al. in patients undergoing elective upper gastrointestinal endoscopy (UGE).  The observed superior effectiveness of the lozenges over the spray could be explained by the continuous release of lidocaine by sucking the lollipop. Swallowing the saliva mixed with the local anesthetic results in homogenous and slow spread of the anesthetic agent and providing ample time to exert its effect on oropharynx. It also exerts its effect on posterior third of the tongue, the area that contains the deep pressure receptors responsible for the gag reflex and this could be one of the reasons for reduced gag reflex in patients who used lozenges. In a study conducted by Mogensen et al., lidocaine lozenge was also associated with reduction in the gag reflex and patients' discomfort as compared to lidocaine spray during UGE. 
In our study, it has been observed that the application procedure of lidocaine lozenges was rated easier as compared to lidocaine spray which is also seen in the study conducted by Ayoub and Baraka. 
Aversive symptoms (especially nausea, vomiting, cough and pain) reported during and after the procedure were also significantly less in lidocaine lozenges group as compared to spray. The more incidence of aversive symptoms reported in lidocaine spray group could be directly related to the additives used in the spray formulation, not with lidocaine as it has been reported by Hara and Maruyama that the additives contained in lidocaine spray causes post procedural sore throat, hoarseness and dysphagia during laryngoscopy.  Our study results suggested that significantly more number of patients preferred to have a repeat procedure with lidocaine lozenge as compared to patients who received lidocaine spray and Investigator and patient's global assessment was significantly more favorable towards lidocaine lozenges than lidocaine spray. This is a reflection of favorable efficacy and safety of lidocaine lozenges compared to spray.
This study was done in adults patients only therefore it does not provide evidence of effectiveness for pediatric patients in whom lozenges is expected to be more convenient than other methods.
Overall, the study suggests that lidocaine lozenge given before awake direct diagnostic laryngoscopy procedure will provide a significant benefit by offering an effective topical anesthesia and translating it into a successful and safe procedure. A lidocaine lozenge is easy to use, safe and effective as compared to lidocaine spray. This unique modality is alternative for providing local anesthesia before awake direct diagnostic laryngoscopy procedure as compared to spray formulation of lidocaine.
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[Table 1], [Table 2], [Table 3], [Table 4]