Efficacy and Safety of Topical Lidocaine 23%/Tetracaine 7% Ointment Versus Placebo for Post-Hemorrhoidectomy Pain: A Double-Blind Randomized Controlled Trial
Efficacy and Safety of Topical Lidocaine 23%/Tetracaine 7% Ointment Versus Placebo for Post-Hemorrhoidectomy Pain: A Double-Blind Randomized Controlled Trial
The goal of this clinical trial is to learn if a topical ointment containing two local anesthetics (lidocaine 23% and tetracaine 7%) can reduce pain after hemorrhoid surgery in adults. The main questions it aims to answer are:
Researchers will compare the lidocaine/tetracaine ointment to a placebo (a look-alike ointment that contains no active drug) to see if the active ointment works better to reduce pain after hemorrhoid surgery.
Participants will:
Background
Hemorrhoidectomy is the most effective surgical treatment for advanced hemorrhoidal disease, but it is associated with significant postoperative pain, particularly during bowel movements. Standard multimodal analgesia regimens, including scheduled non-steroidal anti-inflammatory drugs, acetaminophen, and opioid rescue doses, often provide incomplete relief, especially during defecation. Topical local anesthetics have been explored as adjuvant analgesic agents in this setting, but commercially available formulations use low concentrations (typically 2-2.5%) that may limit their efficacy. High-concentration compounded formulations containing lidocaine 23% and tetracaine 7% have demonstrated an adequate pharmacokinetic safety profile in other clinical settings, but had not been evaluated in proctological surgery prior to this trial.
Study Design
This was a single-center, double-blind, placebo-controlled randomized controlled trial (RCT) conducted at a private academic institution in Santiago, Chile. Participants were randomized in a 1:1 ratio to receive either active ointment (lidocaine 23%/tetracaine 7%) or an identical-appearing placebo ointment. Randomization was performed using a computer-generated sequence with allocation concealment via an encrypted randomization. Both participants and the surgical team were blinded to treatment allocation throughout the follow-up period. The ointments were prepared and labeled by an independent compounding pharmacy, and were identical in color, texture, and packaging.
Intervention
Participants in the intervention group applied approximately 2 g of the lidocaine 23%/tetracaine 7% ointment to the perianal area every 12 hours, beginning on the day of surgery (postoperative day 0) and continuing through postoperative day 10. Participants in the control group applied an identical-appearing placebo ointment following the same schedule. All participants received a standardized perioperative analgesic protocol consisting of scheduled oral ketorolac and acetaminophen, with oral tramadol (25 mg per dose) as rescue analgesia available on demand. Surgical technique was standardized across participating surgeons; trainees operated under direct supervision of board-certified colorectal surgeons.
Outcomes and Measurements
Pain was assessed using a 0-10 visual analogue scale (VAS). Two pain dimensions were recorded daily by participants in a structured paper diary. Post-defecatory pain was recorded as a VAS score immediately after each bowel movement; on days with more than one bowel movement, the mean score was used; on days without a bowel movement, no score was recorded for this dimension. Mean daily pain was recorded as the average VAS score across the entire day, noted each evening. Rescue opioid use was recorded daily as the number of tramadol doses taken. Adverse events were recorded at each follow-up contact and at the end of the 10-day period. Follow-up was conducted by a dedicated research assistant via telephone and messages. Participants were also asked to return their completed diary at the day-10 contact.
Sample Size
Sample size was calculated to detect a clinically relevant 25% reduction in post-defecatory pain, assuming a mean VAS score of 6.6 (SD 2.2), with a two-sided significance level of 0.05 and 80% power, yielding 56 evaluable participants (28 per group). Accounting for an anticipated 10% loss to follow-up, target enrollment was set at 62 patients.
Statistical Analysis
All analyses were performed on an intention-to-treat basis. Continuous variables were compared using the independent samples Student's t-test after confirming normality with the Shapiro-Wilk test and homogeneity of variance with Levene's test. The t-test with equal variances assumed was applied consistently across all time points of each outcome variable to maintain methodological consistency. Categorical variables were compared using Pearson's chi-square test. Period averages for post-defecatory pain (days 1-5 and days 1-10) were calculated as the mean of available daily scores per participant. Daily mean overall pain for the 10-day period was calculated from the pre-specified composite variable. Statistical significance was set at p < 0.05 (two-tailed). All analyses were performed using IBM SPSS Statistics version 29.
Safety Considerations
Prior to trial design, the pharmacokinetic profile of the lidocaine 23%/tetracaine 7% formulation was reviewed. Published data indicate that peak plasma lidocaine concentrations remain below the recognized toxicity threshold of 2 mcg/mL when the formulation is applied to surface areas under 250 cm². In this trial, participants applied approximately 2 g to a perianal surface area of 10-30 cm², representing a substantially lower dose than those associated with systemic toxicity. Participants with conditions associated with increased risk of local anesthetic toxicity (significant cardiovascular, cerebrovascular, or hepatic disease; seizure disorders) were excluded from enrollment. Plasma lidocaine levels were not routinely measured given the low dose used.
Inclusion Criteria:
Exclusion Criteria: