Topical Anaesthesia in Cutaneous Head and Neck Surgery: a Randomized Controlled Trial
Phase: NA
Conditions: Pain, Acute, Head and Neck Cancer, Cutaneous Tumor
Sponsor: University Hospital Waterford

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Research protocol 
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20th December 2022 
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Title: 
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Use of topical anaesthetics in cutaneous head and neck malignancies: a randomized 
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controlled trial 
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Investigators: 
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1. O’Neill RJ 
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2. Affendi A 
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3. McHugh N 
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4. Skinner LJ 
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Corresponding investigator: 
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Rory O’Neill, 
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Department of Otolaryngology 
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University Hospital Waterford 
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Dunmore Road, 
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Waterford, 
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Ireland 
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Email: oneillrjj@gmail.com 
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1. Background: 
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Operations on cutaneous tissues of the head and neck are some of the most frequently 
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performed types of operation performed. They can often successfully be performed using 
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local anaesthetic (LA). However, tissues in this anatomic area are some of most sensitive 
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tissues in the body to nociceptive pain. As such, local anaesthetic can be a distressing 
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experience for patients in many ways. Unfortunately, it is also the most common anatomical 
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site for cutaneous malignancies. Advanced age and chronic sun exposure are two potent risk 
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factors. The majority of these lesions are resected under local anaesthetic for several reasons 
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including economic, patient-factors, theatre availability and speed. However, one of the 
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major disadvantages of local anaesthetic such as lidocaine is pain during administration. This 
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is exacerbated as the head and neck area is one of the most sensitive parts of the body.  
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Several interventions have been used to reduce pain from needles and injections including 
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ethylene chloride cryoanalgesic spray and topical anaesthetic agents including EMLA 
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(lidocaine and prilocaine) and Ametop ointments. These have been extensively used in 
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paediatric populations with great success to reduce pain during procedures requiring 
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hypodermics such as cannulation. Several studies have trialled these interventions in adult 
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populations across a variety of anatomical locations with variable results. 
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1.1.Hypothesis: 
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EMLA and ethyl chloride reduce pain associated with local anaesthetic administration 
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1.2. Aim 
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The aim of this study is to assess if ethylene chloride or EMLA are effective in reducing the 
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pain associated with local anaesthetic administration 
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2. Outcome Measures 
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2.1. Primary outcome measure: 
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The primary outcome measure is patient reported pain on a numeric rating scale (NRS) (1; no 
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pain, 10; worst pain imaginable) 
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2.2.Secondary outcome measures: 
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Patient satisfaction measured on NRS scale of 1=not bad at all, to 10=worst experience 
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imaginable. 
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Analysis of risk factors associated with pain from local anaesthetic in the head and neck 
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including size of resection and injection volume: 
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 Pathology – malignant versus benign 
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 Local anaesthetic volume 
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 Size of resection 
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 Site of resection 
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3. Methodological design 
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3.1. Study design 
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Randomized controlled trial 
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3.2. Selection: 
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Patients will be selected from those attending scheduled excision of cutaneous head and neck 
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malignancies at our centre 
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3.3.Inclusion criteria: 
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 Aged at least 18 years 
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 Receiving surgery to cutaneous tissues of the head and neck 
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 Procedure performed under local anaesthetic 
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3.4.Exclusion criteria: 
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 Paediatric patients 
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 Surgery performed under general anaesthetic 
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 Mucosal operative site (e.g. oral cavity) 
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 Significant cognitive impairment (e.g. severe dementia) 
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 Known sensitivity/allergy to EMLA 
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 History of a pain disorder (e.g. complex regional pain syndrome). 
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3.5.Sample size calculation: 
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A formal sample size calculation will be performed after an initial pilot study of ten patients 
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per group to calculate the effect size. Other studies on using topical anaesthetic agents in 
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other non head and neck anatomical sites typically required less than 50 participants per 
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group. G*Power 3.1 (Universität Düsseldorf) software will be used to calculate the necessary 
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sample size. We will likely employ an α error probability of 0.05 and a power of 95%. A 10% 
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margin for safety will be used to mitigate the possible risks of participant attrition 
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3.6.Randomization: 
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Computer randomization will be performed. A random number sequence will be generated 
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using randomizer.org® with numbers allocated using stratified permuted blocks of four and 
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these will be concealed in individual sealed envelopes with the aid of a research contributor. 
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Participants will be allocated in order of recruitment and in participants with more than two 
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lesions will have the more superiorly located lesion allocated first.  
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3.7.Interventions 
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Patients will be split into 4 groups:  
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 EMLA 
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 Aqueous ointment 
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 Ethyl chloride spray 
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 no treatment.  
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3.8.Study procedures 
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Written informed consent will be obtained prior to group allocation. Following group 
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allocation, topical agents will be administered as follows. EMLA (EMLA cream 5% 25g 
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lidocaine, 25g prilocaine) and aqueous cream will be applied to cover the surgical site, 
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delivered via an unmarked syringe to achieve single blinding. A Tegaderm® adhesive 
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dressing will then be applied over this to prevent the cream from drying out, and it will be 
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removed in the theatre before the administration of LA. The local anesthetic to be used will 
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be 1% lidocaine with 1:200,000 adrenaline and will be injected via a 25-gauge needle 
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attached to a 10ml syringe. A 5ml syringe will be occasionally used when it is not possible to 
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inject via a 10ml syringe. 
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EC will be applied to the surgical site before LA injection. The area will be sprayed at a 
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distance of 5-10cm for 4-8 seconds until the skin slightly blanches, and the fluid will be 
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allowed to evaporate. 
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3.9.Assessing outcomes 
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The key focus in this study will be the assessment of pain linked to the injection of local 
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anesthesia (LA). Following the LA administration, each participant will be prompted to 
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evaluate the pain they undergo using a numeric rating scale (NRS; 1=no pain, 10=worst pain 
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imaginable). Subsequent to the procedure, patients will be inquired about their overall 
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perception of the experience (1=not bad at all, 10=worst experience imaginable). 
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4. Statistical analysis 
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The distribution pattern of variables will be assessed using the Kolmogorov-Smirnov test. 
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The Kruskal-Wallis test and Mann Whitney test will be employed to compare groups for non-
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parametric data and for covariate analysis. The Chi-squared test will be applied to detect 
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differences for categorical data. Spearman’s Rho will be used to quantify the strength of the 
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linear relationship between non-parametric continuous variables. A per protocol analysis will 
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be conducted as it is believed that in cases where patients are unable to describe their pain by 
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using a number, it will disproportionately affect the results by conducting a “worst case 
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scenario” analysis. Furthermore, due to a minimal interval between intervention and 
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measurement of pain outcomes in this study, there will be low rates of attrition. Statistical 
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analysis will be performed using SPSS v.26 (Aramonk, US). Statistical significance will be 
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considered at p<0.05. 
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5. Miscellaneous 
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5.1.Ethical considerations: 
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This trial will be registered with the University Hospital Waterford Research and Ethics 
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Committee where full ethical approval will be obtained prior to study commencement. It 
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is considered that patient risks from this study are negligible. 
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5.2. Funding: 
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No funding will be necessary for this study 
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5.3. Dissemination of results 
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Results will be prepared into a scientific manuscript for publication and presented at 
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scientific surgical meetings 
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