Role of Topical Application of Lignocaine Versus 0.2% Glyceryl Trinitrate (GTN) Ointment as a Postoperative Local Analgesic in Hemorrhoidectomy in Terms of Pain Score,Wound Healing Time and Patient Satisfaction Level
Phase: NA
Conditions: Hemorrhoid, Postoperative Pain
Sponsor: King Edward Medical University

                             Study Protocol with Statistical Analysis Plan 
Official Study Title: Role of Topical Application of Lignocaine versus 0.2% 
Glyceryl Trinitrate (GTN)Ointment as a Postoperative Local Analgesic in 
Hemorrhoidectomy in Terms of Pain Score,Wound Healing Time and Patient 
Satisfaction Level 
NCT Number: [To be Assigned] 
Document Type: Study Protocol with Statistical Analysis Plan 
Document Date: June 2, 2025 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
                                                        

                                                             TITLE: 
Role of Topical Application of Lignocaine Versus 0.2% Glyceryl Trinitrate 
(GTN) Ointment as a postoperative local analgesic in hemorrhoidectomy in 
terms of pain score,wound healing time and patient satisfaction level . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Introduction 
Hemorrhoid are distension of normal hemorrhoidal venous cushions with equal 
incidence rate in both sexes and a prevalence rate of 4.4% with nearly 37 
hemorrhoidectomies per 100,000 people per year. (1) Hemorrhoid are surgically 
managed most commonly by Milligan-Morgan hemorrhoidectomy. It had a major 
complain of post-operative pain limiting the post-operative mobility and delayed 
return to daily routine activities. (2) 
Different modalities had been applied to reduce the post-hemorrhoidectomy pain as 
anal dilatation and internal sphincterotomy. However, these procedures being 
invasive required specialized equipment and could cause irreversible sphincter 
damage leading to flatus and stool incontinence. Non-steroidal anti-inflammatory 
drugs (NSAIDS) and opioids had beneficial effect and are required in high dose, 
resulting in gastrointestinal effects. Multiple topical preparations as nifedipine, 
botulinum toxin, metronidazole and lignocaine had been used successfully. (3) 
Post-hemorrhoidectomy pain depends on various factors as surgical technique, post-
operative analgesia, usage of stool softeners, adequate education and subjective pain 
threshold. Internal anal sphincter (IAS) is innervated by nitric oxide (NO) releasing 
neurons. Stimulation of these nerves result in the release of NO which then cause 
relaxation of the IAS by relaxing smooth muscle. The reduction of IAS spasm and 
reduced pressure will increase anodermal blood flow and therefore improve wound 
healing. Exogenous GTN ointment is an NO donor which relaxes the IAS and thus 
reduces pain.  (4) Many studies have evaluated the analgesic efficacy of 0.2% GTN 
ointment on post-hemorrhoidectomy pain. (3) Lignocaine is an amide local 
anesthetic agent, commonly used for local and topic anesthesia. The site of action of 
lignocaine is at sodium ion channels on the internal surface of nerve cell membranes. 
(5) Kwok et.al reported that pain scores were reduced at 1 hour for the lidocaine (OR 
4.15 [1.12-15.41]; p = 0.03) and compared with placebo (OR 3.85 [1.05-14.11]; p = 
0.04). (6) Xu et.al reported that the post-operative use of lidocaine after the 
endoscopic rubber band ligation had lower VAS score as 0.80 ± 0.42 in comparison 
to the control group with VAS score as 4.11 ± 1.37. (7) Franceschilli et. al found 
that the application of 0.4% GTN after haemorrhoidectomy had a mean VAS score 
of  4.1 ± 1.8 lower than the control group with a mean VAS score of  7.5 ± 1.4 (p < 
0.001). (4)  Khan et.al had reported statistically significant reductions in pain scores 
and quantity of analgesics used from the first to the fourth post-operative days in 
patients using combination of 0.2% GTN and 2% lignocaine as a topical application 

post-operatively in Milligan-Morgan hemorrhoidectomy.  The pain scores on basis 
of 100 mm VAS in lignocaine group were 45.62, 26.88, 18.44 and 10.16 and in GTN 
group 45.9, 31.48, 15.9 and 10.16 on days 1, 2, 3, and 4 respectively. Patients had a 
mean healing time of 4.51 ± 0.744 weeks for 0.2% GTN group and 5.08 ± 0.762 
weeks for 2% lignocaine group. The difference was highly significant between GTN 
and lignocaine groups (p < 0.001). (3) Kwok et. al reported that the topical 
application of lidocaine/ diltiazem after band ligation of hemorrhoids had higher 
satisfaction level (OR 3.82 [1.28–11.44]; p = 0.02). (6) When comparing lignocaine 
and glyceryl trinitrate (GTN) ointment as postoperative local analgesics for 
hemorrhoidectomy, the rationale for this study is based on the need to identify the 
most effective and safe pain management options for patients. Hemorrhoidectomy, 
while effective, often results in significant postoperative pain, which can be 
challenging to manage and may affect recovery and patient satisfaction. Therefore, 
choosing the right local analgesic can play a critical role in improving the patient 
experience and reducing the overall burden on healthcare resources. By exploring 
the relative efficacy and safety of lignocaine versus GTN ointment, this study can 
provide guidance for clinicians on optimizing postoperative pain management 
strategies in hemorrhoidectomy, potentially improving patient outcomes and 
enhancing the overall care experience. 
 
 
 
 
 
 
 
 
 
 
 
 

Objectives  
To compare the outcome of lignocaine versus 0.2% GTN ointment in  post-
hemorrhoidectomy patients as a local analgesic. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Hypothesis 
There is a difference in the outcome of lignocaine vs 0.2% GTN in ointment post- 
hemorrhoidectomy patient as a local analgesic.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Operational Definitions 
Outcomes : 
 will be determined in terms of 
1.Mean Pain Score(VAS) 
Pain in the post operative period will be assessed by VAS (visual analogue scale) on 
a scale of 0 to 10, with 0 showing no pain and 10 showing maximum pain. It will be 
used to assess the severity of pain at 6,12,24,48,72 hours and on 7th , 14th , 21st and 
28th  day after surgery. 
 
 
2.Time to Complete Wound Healing 
Complete epithelization of wound will be labelled as complete wound healing and 
will be measured as the time in days required for complete epithelization. 
 
 
 
 
 
 
 
 

Materials and Methods 
Study Design 
Randomized clinical trial 
Study Setting 
Department of Surgery, Mayo Hospital, Lahore 
Duration of Study 
3-6 months after the approval of synopsis  
Sampling Technique 
Non Probability purposive 
Sample Size Calculation 
A total sample size of 64 is calculated with 32 participants in each group with the 
mean of healing time in group A as 5.08 ± 0.762 and the mean of healing time in 
group B as 4.51 ± 0.744. By using the power as 80% and 95% confidence interval. 
(3) 
Formula 
Mean of group A = 5.08 ± 0.762 
Mean of group B = 4.51 ± 0.744 
Type I error (α) = 0.05 
Type II error (β) = 0.2 
Power = 80% 
 
 
 
 
 
 

Inclusion criteria 
The inclusion criteria for participation includes: 
• Age between 18 – 60 years 
• Both genders 
• Grade III and IV hemorrhoids diagnosed on the basis of history and clinical 
examination by consultant Surgeon.(Grade III Hemorrhoid manually 
reduced by patient with finger and Grade IV is prolapsed) 
• ASA (American society of Anesthesia) grades I, and II 
 
Exclusion criteria 
The exclusion criteria for participation includes: 
• Previously reported allergy or reaction to lignocaine and GTN 
• Pregnancy or lactation 
• Concomitant perianal pathology warranting surgery 
• Cardiovascular disease 
• Patient taking Nitrates or Calcium channel blocker 
 
 
 
 
 
 
 
 
 
 
 
 

Data Collection 
After ethical approval of the study from the institutional review board, the patients 
presenting to Department of Surgery, Mayo Hospital, Lahore with the diagnosis of 
hemorrhoid confirmed on history, and examination will be included in the study. 
Patients’ information such as name, case number, age, gender, and duration of 
hemorrhoids will be inquired. Informed consent will be acquired from the patients. 
The patients will undergo hemorrhoidectomy by the consultant general surgeon or 
by post-graduate general surgery residents under supervision of consultants. 
The participants will be divided by using the lottery method in two groups: Group 
A and Group B. The double blinding will be used to reduce the bias in the study. 
The patients in each group will undergo Milligan Morgan hemorrhoidectomy under 
spinal anesthesia/ saddle block/GA. Following intervention will be done:  
Group A = Lignocaine cream post-operatively and then three times daily 
Group B = 0.2% GTN ointment postoperatively and then three times daily 
All patients will be advised to take sitz bath three times daily for 15 minutes from 
1st post-operative day. They will be advised to apply the prescribed ointment with 
the fingertip circumferentially 1 cm in side the anal canal after sitz bath and to use 
stool softeners (30ml lactulose twice daily). All patients will be given injection 
Paracetamol 1gm intravenously 8 hourly as a standard analgesia. Injection Ketorolac 
30mg intravenously stat as a rescue analgesia in first 24 hour. The patient will be 
discharged on 2 tablet Panadol three times a day. 
 The outcome will be measured by using the visual analogue score (VAS) for 
analgesia will be used to assess the score of pain at 6, 12, 24, 48, 72 hours and on 
7th, 14th, 21st and 28th day after surgery. Time of request for 1st dose of analgesia, 
and amount of analgesia required as per demand of the patient will be documented 
within 1st 24 hours. Patients will be discharged after 24 hours with pain evaluation 
performa and will be followed weekly for 6 weeks to assess the level of pain and 
healing of wound. The level of satisfaction of patient with treatment will be 
assessed after 6 weeks on a 5-point Likert scale. 
 
 
 

Data Analysis 
All data will be analyzed using Statistical Package for the Social Sciences (SPSS) 
ver. 26. Quantitative variables as age, pain score and wound healing time will be 
presented as mean ± standard deviation and qualitative variables as gender and 
satisfaction level of patient will be displayed as frequency and percentage. Data 
will be stratified for age,gender,BMI,Grade of Hemorrhoids. Independent sample t-
test will be applied post-stratification. A p-value < 0.05 will be considered as 
significant. 
                                                   
                                                 
 
                                                          
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                               Performa  
Role of Topical Application of Lignocaine Versus 0.2% Glyceryl Trinitrate 
(GTN) Ointment as a postoperative local analgesic in hemorrhoidectomy in 
terms of pain score,wound healing time and patient satisfaction level  
Name:                                                              Age/gender: 
Mr No:                                                             Address: 
Date of surgical procedure:                             ASA Score: 
Group:     A/B                                                  BMI: 
Grade of Hemorrhoid; 
PRIMARY OUTCOMES: 
Pain Score,wound Healing time  is a primary outcomes  
Other Variables: 
• Time for request of 1st dose of analgesia:--------------------min/hr 
• Amount of analgesia given in 24 hours:------------------mg 
Level of satisfaction of patient after 6 weeks: 
• Very satisfied 
• Satisfied 
• Neutral 
• Dissatisfied 
• Very dissatisfied 
Wound healing time: -----------------days 
Time after 
procedure  
6 
hr 
12 
hr 
24 
hr 
48 
hr 
72 
hr 
 7  
Day 
14 
day 
21 
day 
28 
day 
Pain Score 
 
 
 
 
 
 
 
 
 
Wound 
infection(Yes/No) 
 
 
 
 
 
 
 
 
 
Secretion(Yes/No)  
 
 
 
 
 
 
 
 
Itching(Yes/No) 
 
 
 
 
 
 
 
 
 
Bleeding(Yes/No)  
 
 
 
 
 
 
 
 
Headche(yes/No) 
 
 
 
 
 
 
 
 
 

References 
1. Asif K, UL-HASSAN M,Muneeb Rehman P,Rasheed T,Zahid L. Compare 
the efficacy of 0.2% topical glyceryl trinitrate (GTN) versus placebo in 
prevention of wound infection in patients undergoing Milligan-Morgan 
hemorrhoidectomy. PJMHS. 2020;34:12-46. 
2. Lashari AA, Bozdar AG, Bhellar ZH, Baker A, Shar ZA, Narejo GA. 
Determine the effectiveness of 0.2% topical glyceryl trinitrate in preventing 
postoperative wound infection after hemorrhoidectomy. Pak J Med Health 
Sci. 2020;14(4):1327-9. 
3. Khan KI, Waqas A, Akmal M, Mahmood S, Iqbal A. Efficacy of 
combination of 0.2% GTN and lignocaine ointments in wound healing and 
pain relief after Milligan Morgan hemorrhoidectomy–a comparison with 
lignocaine and 0.2% GTN ointments separately. Int J Surg. 2014 
;12(4):329-33. 
4. Franceschilli L, D’Ugo S, de Luca E, Cadeddu F, Milito G, Di Lorenzo N, 
“et al”. Role of 0.4% glyceryl trinitrate ointment after haemorrhoidectomy: 
results of a prospective randomised study. Int J of colorectal dis. 
2013;28:365-9. 
5. Sekimoto K, Tobe M, Saito S. Local anesthetic toxicity: acute and chronic 
management. Acute Med Surg. 2017;4(2):152-160 
6. Kwok AM, Smith SR, Zhao J, Carroll R, Leigh L, Draganic B. Topical 
Lidocaine or Lidocaine/Diltiazem Ointment Following Rubber Band 
Ligation of Hemorrhoids: A Prospective 3-Armed Randomized Controlled  
Trial. Dis Colon Rectum. 2023;66(8):1110-7. 
7. Xu W, Xia G, Dong L, Zhu Y. Effect of lidocaine on postoperative 
analgesia of endoscopic rubber band ligation combined with injection 
sclerotherapy for treatment of internal hemorrhoids: A retrospective study 
s(with video). Arab Journal of Gastroenterology. 2024 May 1;25(2):165-9.