Topical Modalities to Reduce Acute Post-Hemorrhoidectomy Pain: A Comparative Clinical Study

Abstract

Introduction

Despite the advances in pain therapy, postoperative hemorrhoidectomy pain is still common and annoying. The present study aims to minimize post-hemorrhoidectomy pain and improve the quality of life.

Materials and Methods

The current study is a single-center, prospective, randomized, comparative clinical trial performed in the General Surgery Department from January to October 2024. The study included 150 hemorrhoidectomy patients randomly allocated to five groups: group I – control group; group II – local injection of ketorolac and light bupivacaine; group III – injection of light bupivacaine; group IV – local injection of corticosteroids; and group V – topical diclofenac sodium gel.

Results

Compared ot the other groups, group IV presented significantly better outcomes (p < 0.001) regarding the need, dose, and frequency of nalufin, postoperative pain score, and time until first ambulation. However, it presented longer healing time than the other groups.

Conclusion

Local injections of corticosteroids can effectively reduce pain after hemorrhoidectomy.

Keywords

hemorrhoidectomy - pain - corticosteroids - bupivacaine - diclofenac sodium

Introduction

The most frequent benign anal condition that doctors and surgeons observe is hemorrhoids.[1] According to some estimates,[2] the general population may have a 75% lifetime risk of developing hemorrhoids. Surgery is recommended for high-grade hemorrhoids or complex illnesses, even though most cases can be successfully treated with medication and/or office-based methods.[3] [4] [5]

Non-excisional procedures, including stapled hemorrhoidopexy, Doppler-guided hemorrhoidal artery ligation, and laser hemorrhoidoplasty, were shown[6] [7] to be less painful than excisional hemorrhoidectomy. The latter, however, was linked to lower cost of surgical tools and lower recurrence rate. Furthermore, hemorrhoidectomy is an effective method of removing the surface and interior components of hemorrhoids.

According to published data,[8] up to 65% of patients may presente with moderate-to-severe pain after a traditional hemorrhoidectomy. Multimodal analgesia and local anesthetic agents can reduce pain. Patient-controlled analgesia and tailored doses of nalbuphine are effective but costly, and they may be misused by the patient, leading to hypotension and gastritis. Topical agents such as diclofenac rectal suppository or cream, topical anesthetic cream, or injection, have also been tried, but with limited effect which lasts for a short time.

A few clinical trials have looked at the effect of botulinum toxin injection on post-hemorrhoidectomy pain, with variable results. Injection of botulinum toxin A into the internal anal sphincter (IAS) has been used to induce a temporary relaxation of the sphincter–instead of its surgical division–which may cause long-term sequelae such as short-term fecal incontinence, which can be annoying.[9]

A double-blinded, randomized controlled trial compared postoperative intradermal injections of 1% methylene blue to 0.5% bupivacaine injection and demonstrated nearly equal results in pain control.[10] Another trial on methylene blue injection was effective in reducing postoperative pain, but only for 3 days post-operatively.[11]

A study[12] comparing the results of oral and local narcotics versus oral and local ketorolac injection demonstrated that the patients in the ketorolac group reported better satisfaction.

However, there are no studies on the role of topical corticosteroid injection in reducing post-hemorrhoidectomy pain. The current study aims to find the best topical agent to reduce it.

Materials and Methods

The present study is a comparative randomized controlled clinical trial. According to the monthly flow rate of patients who met the inclusion criteria and with 80% of power and 95%CIs, 150 patients were included in the study and underwent hemorrhoidectomy from January 2024 to October 2024. They were randomly classified into five groups: group I –control group; group II – local injection of ketorolac and light bupivacaine; group III – injection of light bupivacaine; group IV – local injection of corticosteroids; and group V – topical diclofenac sodium gel. Block randomization was performed, and the lottery method was used for randomization to select an option out of five for every patient. The participants were blinded to the method selected.

The current study followed the 2010 Consolidated Standards of Reporting Trials (CONSORT) guidelines[13], with protocol registration #40\14-Jan-2024, and it was registered at ClinicalTrials.gov (NCT06307106). The study included patients of both sexes, older than 18 years of age, with grade-3 to -4 internal hemorrhoidal disease (which required surgery), and most subjects presented bleeding, pain or both. Patients with grade-1 and/or -2 diseases were included when they presented symptoms, or for cosmetic purposes. Patients who refused to provide informed consent, those with proven malignancy or inflammatory bowel disease (IBD), aged under 18 years, who had contraindications to general or spinal anesthesia, subjects with combined anal fissures and hemorrhoids or those with associated fistula or abscess, as well as patients eligible for conservative treatment, or those with thrombosed or recurrent hemorrhoids, were excluded from the study.

The patients were diagnosed in the outpatient clinic with different degrees of hemorrhoids that required surgery; they were admitted and underwent the routine preoperative investigations. The patients fasted for 6 hours preoperatively and received an enema, as well as metronidazole 500 mg 3 times a day 5 days before the procedure. Just before the operation, a vial of 1 g of ceftriaxone was administered to the patients as a prophylactic antibiotic.

To exclude technical bias, hemorrhoidectomy was performed by the same surgeon and under saddle anesthesia. All patients underwent open (Milligan-Morgan) hemorrhoidectomy using a diathermy device (MEDITOM, MT-400) and VICRYL 3-0 (Johnson & Johnson MedTech). The hemorrhoid pulp was excised along the mucocutaneous junction using monopolar diathermy until the pedicle, which was ligated by a transfixing suture using VICRYL 3-0.

Immediately after surgery, in the operative theatre, the patients were classified as follows:

Group I – no topical agent (control group).

Group II: Subcutaneous site injection of ketorolac (30 mg per dose) and light bupivacaine (0.7–1.5 mg/kg per dose) at the sites of the excised hemorrhoids and in the intersphincteric space at 3 and 9 o'clock.

Group III: subcutaneous injection of light bupivacaine (0.7–1.5 mg/kg per dose) at the sites of the excised hemorrhoids and in the intersphincteric space at 3 and 9 o'clock.

Group IV: subcutaneous injection of corticosteroids (40 mg of dexamethasone per dose) at the sites of the excised hemorrhoids and in the intersphincteric space at 3 and 9 o'clock.

Group V: topical diclofenac sodium gel.

Anal pack with a sterile gauze was placed in all cases for homeostasis. The onset, frequency, and dose of additional analgesia were assessed by using diluted nalbuphine on demand (1 mL in 10 mL of normal saline). The patients received postoperative antibiotics, soft diet for 3 days, and laxatives, and they were informed to detect when they had their first ambulation (walk without support). Intra- and postoperative bleeding were assessed through gravimetric methods by weighing the gauze before and after soaking. Continence was assessed by asking the patient a direct subjective question. The anal pack was removed after 12 hours, and the patients were discharged 24 hours after surgery. Pain assessment was performed through the Visual Analogue Scale (VAS) in the first 3 postoperative days, as well as in the 7th and 14th days. The patients were followed up for 3 months.

Statistical Analysis

The IBM SPSS Statistics for Windows application (IBM Corp.), version 27.0, was used for statistical analysis. Frequencies and relative percentages were used to express the qualitative data, and mean ±  standard deviation (SD) values were used to express the quantitative data. The results were considered significant if the p < 0.05, and highly significant if p < 0.001. One-way analysis of variance (ANOVA) and the Chi-squared test were used to analyze the qualitative and quantitative data respectively. The Kruskall-Wallis and Friedman tests were used to calculate the interquartile range (IQR).

Results

The 150 patients who formed the sample were divided into 5 groups, with 30 patients in each group. There were no statistically significant differences among the groups regarding age, sex, and degree and number of hemorrhoids, as shown in [Table 1].

Table 1 Baseline characteristics of the study sample

Variable	Group I (n = 30)	Group II (n = 30)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value
Mean age in years (range)	37.3 ±  6.5 (27–48)	36.6 ±  6.3 (22–49)	34.5 ±  6.2 (23–46)	37.8 ±  6.9 (21–48)	38.7 ±  7.3 (22–49)	0.159#
Sex – n (%): female; male	14 (46.7%); 16 (53.3%)	14 (46.7%); 16 (53.3%)	18 (60%); 12 (40%)	13 (43.3%); 17 (56.7%)	14 (46.7%); 16 (53.3%)	0.731*
Degree – n (%): 2; 3; 4;	1 (3.3%); 29 (96.7%); 0 (0%)	0 (0%); 27 (90%); 3 (10%)	0 (0%); 24 (80%); 6 (20%)	0 (0%); 26 (86.7%); 4 (13.3%)	0 (0%); 27 (90%); 3 (10%)	0.240*
Number 1; 2; 3;	1 28 1	0 28 2	0 30 0	0 29 1	1 26 3	0.3041

Notes: ^#One-way analysis of variance (ANOVA). *Chi-squared test.

There were highly significant differences among the groups regarding the first administration of nalbuphine, the number of shots needed, the timing of the last shot, and the dose of nalbuphine, which all were found to be significantly lower in group IV compared to the other groups, as shown in [Table 2]. The time until the first ambulation is shown in [Table 3] .

Table 2 Nalbuphine requirement in the study sample

Variable: n (%)	Group I (n = 30)	Group II (n = 30)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value#
First administration: after 8 hours; no need	30 (100%); 0 (0%)	29 (96.7%); 1 (3.3%)	30 (100%); 0 (0%)	2 (6.7%); 28 (93.3%)	30 (100%); 0 (0%)	< 0.001**
Number of shots: 1; 2; None	0 (0%); 30 (100%); 0 (0%)	11 (36.7%); 18 (60%); 1 (3.3%)	7 (23.3%); 23 (76.6); 0 (0%)	2 (6.7%); 0 (0%); 28 (93.3%)	1 (3.3%); 29 (96.7%); 0 (0%)	< 0.001**
Last shot:* After 8 hours; After 12 hours; After 16 hours; After 18 hours; No need	0 (0%); 0 (0%); 30 (100%); 0 (0%); 0 (0%)	11 (36.7%); 1 (3.3%); 0 (0%); 17 (53.6%); 1 (3.3%)	7 (23.3%); 0 (0%); 23 (76.7); 0 (0%); 0 (0%)	2 (6.7%); 0 (0%); 0 (0%); 0 (0%); 28 (93.3%)	1 (3.3%); 3 (10%); 26 (86.7%); 0 (0%); 0 (0%)	< 0.001**
Nalubphine dose: 2 mL; 4 mL; No need	0 (0%); 30 (100%); 0 (0%)	11 (36.7%); 18 (60%); 1 (3.3%)	6 (20%); 23 (76.7); 1 (3.3%)	2 (6.7%); 0 (0%); 28 (93.3%)	1 (3.3%); 29 (96.7%); 0 (0%)	< 0.001**

Notes: ^#Chi-squared test; *shot: 2 mL of diluted nalbuphine; **highly-significant difference.

Table 3 Time until first ambulation in the study sample

Variable: n (%)	Group I (n = 30)	Group II (n = 30)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value#
First ambulation: after 6 hours; after 8 hours	0 (0%); 30 (100%)	9 (30%); 21 (70%)	4 (13.3%); 26 (86.7)	29 (96.7%); 1 (3.3%)	8 (26.7%); 22 (73.3%)	< 0.001**

Notes: ^#Chi-squared test; **highly-significant difference.

[Table 4] shows that there were highly significant differences among the groups regarding the VAS pain scores after operation and on the first, second, and third days, as well as in the first week, which all were found to be significantly lower in group IV compared to the other groups (p < 0.001). However, there were no significant differences among the groups regarding the VAS score after 2 weeks of the operation. By comparing the VAS scores at different times in each group, we noticed they decreased significantly as time passed.

Table 4 Score on the Visual Analog Score (VAS) at different times

Variable: median (interquartile range)	Group I (n = 30)	Group II (n =3 0)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value#
8 hours postoperatively	8 (7–8)	7 (7–8)	7 (7–7)	3 (3–4)	7 (7–7)	< 0.001**
Postoperative day 1	8 (7–8)	6 (6–8)	6 (5–6)	3 (2–4)	6 (6–6)	< 0.001**
Postoperative day 2	7 (7–8)	6 (5–6)	6 (5–6)	3 (0–3)	6 (6–6)	< 0.001**
Postoperative day 3	7 (6–7)	4 (3–4)	4 (4–4)	0 --	4 (3–5)	< 0.001**
1 week postoperatively:	2 (2–2)	0 --	0 --	0 --	0 --	< 0.001**
2 weeks postoperatively	0 --	0 --	0 --	0 --	0 --	1.00
p-value*	< 0.001**	< 0.001**	< 0.001**	< 0.001**	< 0.001**

Notes: ^#Kruskall-Wallis test; *Friedman test; **highly-significant difference.

There were no significant differences among the groups regarding postoperative continence and bleeding ([Table 5]), but there were highly significant differences regarding the time required for healing ([ Table 6]). Complete healing was assessed through the observation of completely smooth mucosal and skin coverings of the wound using PR and local examination using a proctoscope (Kelly's rectal speculum). Group IV showed retarded healing compared to the other groups.

Table 5 Complications in the study sample

Variable; n (%)	Group I (n = 30)	Group II (n = 30)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value*
Continence: yes; no	30 (100%); 0 (0%)	30 (100%); 0 (0%)	30 (100%); 0 (0%)	30 (100%); 0 (0%)	30 (100%); 0 (0%)	> 0.999
Bleeding: yes; no	0 (0%); 30 (100%)	0 (0%); 30 (100%)	0 (0%); 30 (100%)	0 (0%); 30 (100%)	0 (0%); 30 (100%)	> 0.999

Note: *Chi-squared test.

Table 6 Healing time in the study sample

Variable	Group I (n = 30)	Group II (n = 30)	Group III (n = 30)	Group IV (n = 30)	Group V (n = 30)	p-value*
Mean healing time in days (range)	58.1 ±  8.5 (45–80)	55.9 ±  8.8 (42–71)	55.5 ±  6.4 (44–70)	73.4 ±  5.8 (63–80)	57.6 ±  6.4 (45–70)	< 0.001**

Notes: *Chi-squared test; **highly-significant difference.

Discussion

Although the precise source of pain following hemorrhoidectomy is yet unknown, it seems to be complex. Pain following a hemorrhoidectomy has been explained by a variety of theories. Internal anal sphincter spasm following fiber exposure is the most common cause; additional causes include anal pack insertion, damage to the anal canal's mucosal lining or nerve endings, suturing at the pedicle or below the dentate line, wound infection, and the formation of an anal fissure.[8] [14] The development of a traumatic neuroma following an open hemorrhoidectomy is an uncommon documented cause of chronic pain, which may linger for several years following the treatment.[15]

Injections of local analgesics such as ketorolac can achieve adequate control of post-hemorrhoidectomy pain. Injection of ketorolac directly into the IAS fibers serves to inhibit its spasm by suppressing prostaglandin formation, in addition to its anti-inflammatory effect.[16]

Post-hemorrhoidectomy pain can also be lessened by locally infiltrating the skin surrounding the anal margin with a long-acting anesthetic such as bupivacaine. When comparing the local infiltration of bupivacaine hydrochloride (HCl) and liposome bupivacaine (LB) following excisional hemorrhoidectomy (EH), Haas et al.[17] found that LB considerably decreased postoperative pain in comparison to bupivacaine HCl.

Abdel-Maksoud[18] found that diclofenac suppository combined with lignocaine cream significantly decreased the severity of postoperative pain after anal surgery and decreased the requirement of postoperative analgesics. To the best of our knowledge, no previous studies tried the use of diclofenac sodium gel and local injection of corticosteroids. In the current study, there were no differences among the five groups regarding age, sex, and the degree of hemorrhoids.

Nalbuphine requirement in the first 8 hours after surgery was significantly reduced in group IV, in which 93% of the patients did not need nalbuphine at all. Moreover, all patients in groups I, III, and V needed nalbuphine in the first 8 hours after surgery, as well as 96.7% of the patients in group II.

Regarding the frequency and dose of nalbuphine, 93.3% of group IV did not require nalbuphine at all postoperatively. Groups I and V presented the highest nalbuphine dose requirements. The administration of nalbuphine was maintained up to 16 hours postoperatively in groups I, III, and V, while group II continued to use nalbuphine up to 18 hours postoperatively. This is not in line with the study by Shahrokhzadeh et al.,[19] study which showed that topical ketorolac and light bupivacaine injections required lower doses of opioids than topical bupivacaine injection alone. The cause is not clear; it may be due to drug-drug interaction, or perhaps the subcutaneous route was not the best site for ketorolac injection, the reason made it even worse than the control group.

After the effect of the saddle anesthesia fades, pain can delay the ambulation of the patient. In the present study, after the effect of anesthesia ended, the earliest ambulation was observed in group IV, followed by group II, and then, group V. However, group II required higher doses of nalbuphine.

Pain was evaluated through VAS 8 hours after the operation, and at the end of the first and second postoperative days; the lowest score was found in group IV, while the highest was found in group I. At the end of the third day, group IV presented a median pain score of 0. After one week, the median pain score was 0 in all groups except group I, which presented a median score of 0 at the end of the second week. This is in line with the study by Chester et al.,[20] who concluded that topical injection of bupivacaine after hemorrhoidectomy provides initial pain relief, but patients do not obtain an overall analgesic benefit.

Regarding the postoperative complications, all patients in the current study were continent. No significant post-operative bleeding was found. The assessment of continence was subjective, but all patients maintained their baseline level after surgery.

In their study on experimental mice, Alberti et al.[21] reported that corticosteroids cause delayed wound healing, but they need to be administrated systemically and preoperatively for a long time.

Few studies[22] have discussed the role of the topical injection of corticosteroids, as the most popular local steroid injection is used mainly to delay or inhibit excessive wound healing, as in the case of keloids. In the current study, steroids were injected for their anti-inflammatory effect, with the expected result of reduction of postoperative pain.

The use of local steroids may result in delayed wound healing by causing dermal and epidermal changes such as thinning of the epithelium, loss of rete ridges, necrosis of epithelial and small blood vessels, interference with synthesis of melanin from melanocytes, reduction of mucopolysaccharides, and loss of elastic properties of tissues.[23]

Healing was followed up for 3 months postoperatively. The fastest healing rate was found in group III, while group IV showed delayed healing compared to the others, but within the normal range. This can be explained by the fact that there was only one session of injection of corticosteroids.

Conclusion

Acute post-hemorrhoidectomy pain reduction can be effectively achieved using local corticosteroid injections. We recommend that future studies try injection of short-acting corticosteroids and prolong the follow-up to assess the long-term outcomes.

Conflict of Interests

The authors have no conflict of interests to declare.

Authors' Contributions

YAO: conceptualization, formal analysis, methodology, project administration, software, supervision, validation and writing – review & editing; MAMR: data curation, investigation and writing – original draft; WMM A: data curation and resources; RZ: data curation, formal analysis, resources, software, supervision, validation, writing – original draft and writing – review & editing; TEAE: methodology, project administration and visualization.

All authors read and approved of the final manuscript.

Data Availability

No datasets were generated or analyzed during the current study.

Ethical Approval

The present study was conducted following the ethical principles of the Declaration of Helsinki 2000, and it was approved by the Institutional Review Board (under number 40\14-Jan-2024), which provided an exemption for informed consent. Clinical Trial registration ID: (NCT06307106).

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Publication History

Received: 03 April 2025

Accepted: 04 August 2025

Article published online:
29 December 2025