Abstract
The healing of haemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of sucralfate ointment on wound healing (epithelialisation) and postoperative pain after open haemorrhoidectomy. This trial involves two groups of randomly collected patients (n = 40) who underwent open haemorrhoidectomy surgery by the Milligan‐Morgan method. A 10% topical sucralfate ointment was applied to the investigated group's wounds, while the control group patients used Vaseline as a placebo. The present work measured the two outcomes as follows: pain severity by a Visual Analogues Scale (VAS) score and epithelialisation by a surgeon's visual inspection. During the postoperative phase, the mean VAS was 3.70 for the investigated group and 6.90 for the control group. On the average, the completion of epithelialisation for the investigated group was on day 13 as opposed to day 20 for the control group. The topical application of sucralfate ointment on post‐haemorrhoidectomy wound is an effective method for the promotion of healing, also lessens the severity of pain, and reduces the need for analgesics.
Keywords: epithelialisation, haemorrhoidectomy, sucralfate, wound healing
1. INTRODUCTION
Symptomatic haemorrhoid disease affects approximately 58% of the general population aged >40 years. This is a common disease that generally requires surgery for treatment. Although conservative treatment is often sufficient for the early stages (Grade I and Grade II) of the disease, the late stages (Grade III and Grade IV) usually call for surgical treatment. Open haemorrhoidectomy is still the most frequently performed operation for haemorrhoids and the most common and effective approaches are the conventional surgical treatments of Milligan‐Morgan (open) and Ferguson.1, 2
Haemorrhoid surgery is often associated with considerable postoperative pain. Opioid analgesics and non‐steroidal anti‐inflammatory drugs are often prescribed for pain control. However, these medications can only be administered for a short time.3, 4
Milligan‐Morgan was the surgical approach used for the patients of the current study. In this technique, after resection of haemorrhoidal tissues, the wound is left open for healing by a secondary mechanism. Until the wound is completely healed (epithelialisation), the patient experiences much discomfort stemming from pain, bleeding, pruritus, and other conditions. 5 The use of various interventions may exacerbate these problems. Several pharmacotherapies have been administered to manage post‐haemorrhoidectomy pain and these include local anaesthetics, nitrates, calcium channel blockers, botulinum toxin, and metronidazole. 4 Although these medications have been shown to be effective in reducing postoperative pain, their use is limited because of different reasons, such as a short duration of efficacy, side effects patients find difficult to bear, low potency, or risks associated with their use. 6
Sucralfate is a basic aluminium salt of sucrose octasulfate which dissociates in weak acidic environments. When applied to a wound, it absorbs bile salts and forms insoluble adherent complexes that protect the wound from mechanical damage. By preventing the release of inflammatory cytokines from damaged epithelial cells, sucralfate also reduces pain. In addition, it has been found to possess antibacterial properties. As a result, in a number of studies, sucralfate has been used to reduce pain and improve wound healing. Encouraging reports about the effects of topical sucralfate on the epithelialisation of wounds and its antibacterial activity convinced the present authors that sucralfate can reduce post‐haemorrhoidectomy pain when topically applied to the wound site.7, 8
The current study investigates the effects of 10% sucralfate ointment on haemorrhoidectomy wound healing and postoperative pain.
2. MATERIALS AND METHODS
This is a randomised ([1:1] balanced block randomisation), single‐blind, parallel‐group clinical trial which was conducted in Birjand University of Medical Sciences, South Khorasan, Iran, and assigned with a registration number by the centre of clinical trials (IRCT20111211008375N17). This investigation has been reported in line with Consolidated Standard of Reporting Trials (CONSORT) guideline and has been funded by our university of medical sciences.
The present study's eligibility criteria were patients with Grade III and IV haemorrhoids who had not responded to medical treatment and had been elected for surgical treatment. Patient age was between 25 and 45 years old. The exclusion criteria included: (a) patients with diabetes, (b) patients with other specific diseases, and (c) patients who were drug abusers. The number of patients totalled 40 and these were randomly divided into two groups of 20.
The current study was conducted in 2018 at the general surgery ward of our department and has been affiliated with our university of medical sciences. After pre‐operation preparations, all patients underwent general anaesthesia and haemorrhoidectomy surgery with the Milligan‐Morgan technique by one general surgeon. For the investigated group, after complete haemorrhoidal excision and homeostasis, gauze with 10% sucralfate was applied to the operation site (inside the anal canal). The soaked gauze contained approximately 1000 mg of sucralfate (Kimidaroo, District 13, Tehran, Tehran Province, Iran). The patients were then transferred to recovery. For the control group, after complete haemorrhoidal excision and homeostasis, gauze with a placebo of Vaseline was applied to the operation site (inside the anal canal). The patients were then transferred to recovery. In both groups, the gauze was kept inside the anal canal for 24 hours after surgery. Two variants were measured: (a) pain severity by a Visual Analogues Scale (VAS) score after 24 hours and then in 4‐day periods until the end of epithelialisation and (b) epithelialisation by a surgeon's visual inspection of the rectum every 72 hours, until complete epithelialisation.
After defecation, the investigated group applied a 10% sucralfate ointment to the operation site each time while the control group used a Vaseline placebo. The ointments were put in identical containers and the patients applied the ointment themselves once a day, if the patients defecated twice or more each day we would divide the amount of ointment in two or more doses so that the total dose in all patients would be 1000 mg sucralfate.
The current study's patients' selection was determined by the patients who had been diagnosed as Grade III and IV haemorrhoids and were deemed eligible for this trial. Randomisation was performed by balanced block randomisation with a 1:1 allocation using random block sizes of 4. The present work is considered as a single‐blind.
2.1. Statistical analysis
SPSS version 22 performed the analyses and the independent t‐test compared the continuous variables. A P value <.05 was considered statistically significant.
2.2. Ethical considerations
The study's procedure was completely explained to the participants and consent forms were obtained. Consent form is consisting of the details of benefits and risks of two methods of surgeries and is signed by all of the patients. This study is approved by the Ethics Committee of Birjand University of Medical Sciences, Reference number: Ir.bums.REC.1395.264.
3. RESULTS
The VAS score was evaluated for two time periods: (a) 24 hours after surgery and (b) after day 1, the mean VAS in 4‐day periods until complete epithelialisation (Tables 1 and 2). The results of the 24‐hour VAS did not hold any significant importance (P value = 0.99), but the mean VAS showed a significant difference (P value < .001). The t‐test after 24 hours indicated no significant difference between the two groups. The mean VAS during the postoperative phase (in 4‐day periods until the end of epithelialisation) for the investigated and control groups was 3.70 ± 0.73 and 6.90 ± 1.33, respectively. The (P value < .001) independent t‐test showed that the amount of pain had significantly reduced in the investigated group.
TABLE 1.
Comparison of the VAS in the two groups 24 hours after haemorrhoidectomy
| Group | Mean ± SD | T | DF | P value |
|---|---|---|---|---|
| Investigated | 6.70 ± 1.42 | 001.0 | 38 | 0.99 |
| Control | 6.70 ± 1.49 |
TABLE 2.
Comparison of the mean VAS after haemorrhoidectomy in 4‐day periods until the end of epithelialisation
| Group | Mean ± SD | T | DF | P value |
|---|---|---|---|---|
| Investigated | 3.70 ± 0.73 | −9.40 | 38 | <0.001 |
| Control | 6.90 ± 1.33 |
The completion of epithelialisation (Table 3) for the investigated group was observed, on the average, on day 13.05 ± 1.93 after surgery. In the control group, epithelialisation occurred on day 20.40 ± 3.51. As a result, there was a significant difference in epithelialisation between the two groups.
TABLE 3.
Comparison of the epithelialisation time after haemorrhoidectomy (in days) for both groups
| Group | SD ± mean | T | DF | P value |
|---|---|---|---|---|
| Investigated | 13.05 ± 1.93 | −8.19 | 29.52 | <0.001 |
| Control | 20.40 ± 3.51 |
4. DISCUSSION
Haemorrhoids are among the most common anorectal complaints. Treatment of haemorrhoids depends on the stage of the disorder and the symptoms. Post‐haemorrhoidectomy symptoms may disturb most patients and are one of the main concerns for surgeons. Post‐haemorrhoidectomy pain has been clinically observed as the most feared symptom among patients and often as a deterrent to surgery altogether. Post‐haemorrhoidectomy pain is also a common cause of prolonged hospital stays.3, 9 Open excisional haemorrhoidectomy is the gold standard for third and fourth degree haemorrhoids. 5
The most significant early postoperative complication after haemorrhoidectomy is bleeding. Immediate haemorrhage occurring during the first 24 hours is usually because of a technical error. The mechanisms of delayed (or secondary) bleeding are less clearly understood. This usually occurs during the second postoperative week and tissue necrosis is implicated.10, 11
Wound healing is another significant factor in the outcome of a haemorrhoidectomy. Wound healing is critical after a Milligan‐Morgan haemorrhoidectomy and the large wound area can delay healing and increase pain.5, 12
Several factors are thought to be involved in the generation of postoperative pain, including the surgical incision, spasm of the internal anal sphincter, incarceration of the smooth muscle fibres and mucosa in the transfixed vascular pedicles, epithelial denudation of the anal canal, and oedema caused by tissue inflammation around the wound. Several pharmacotherapies have been used for the management of post‐haemorrhoidectomy pain, but the results have not been satisfactory. 3 The benefits of applying topical agents have been observed in the wound healing process.
Currently, most surgeons do not use any kind of topical agents to reduce the pain after a haemorrhoidectomy. Among various other drugs, sucralfate appears to possess analgesic effects. Topical preparations of sucralfate have been used to reduce pain and accelerate wound healing under several conditions, including radiation‐induced mucositis, second and third degree burns, giant refractory solitary rectal ulcer syndrome, and anal fistulotomy. 6
In addition to providing cytoprotection and preventing the release of inflammatory cytokines, sucralfate is also known to accelerate wound healing and reduce pain by stimulating angiogenesis and fibroblast proliferation, which are of crucial importance for the generation of granulation tissue and wound healing processes. Sucralfate promotes both epidermal growth factor and basic fibroblast growth factor (bFGF) concentrations in wounds. It binds with bFGF and stabilises it in a manner similar to that of heparin. Stabilised bFGF stimulates the formation of small blood vessels and activates cell division of fibroblast and epidermal cells.8, 13
The present study evaluated the effects of 10% topical sucralfate on wound healing and post‐haemorrhoidectomy pain. The current work reported that the investigated group's VAS scores, which were obtained in 4‐day periods until the end of epithelialisation, significantly decreased during the post ‐operative phase.
In addition, Mirani et al reported that 48 of their patients experienced a significant analgesic effect from topical sucralfate ointment (10%) and a reduction in both acute and chronic pain after haemorrhoidectomy. Gahlot et al made the same observation. 14 Gupta et al studied the effect of a 7% topical sucralfate cream on postoperative pain and healing after open haemorrhoidectomy. Their sucralfate group showed better overall healing and experienced less pain on postoperative days 7 and 14 in comparison with the placebo group.6, 14
As mentioned earlier in the current study, sucralfate interacts with several factors involved in wound healing, including stimulation of prostaglandins, local blood flow, epithelial growth factors, and cell migration. For the treatment of oral and genital ulceration in patients with Behçet disease, Alpsoy et al topically applied a sucralfate suspension. Their study reported on the efficacy of this treatment. 15 For the healing of haemorrhoidectomy wounds, Gupta et al investigated if there were any advantages in applying a topical application of sucralfate. Their research found this treatment to be satisfactory. 16
Topical sucralfate treatment significantly reduced pain after haemorrhoidectomy and induced faster wound healing when compared with the placebo. 17 Another research, however, demonstrated that sucralfate does not ameliorate acute radiation proctitis. In Hovdenak et al's unplanned interim analysis of 44 evaluable patients, the sucralfate group experienced a significant increase in diarrhoea, thus prompting the trial to stop.
As a result, sucralfate cannot be recommended for the prophylaxis of acute radiation procto‐pathy; moreover, the symptoms may even worsen. 16
5. CONCLUSION
The current study observed that the completion of epithelialisation for the investigated group occurred significantly faster than it did for the control group, by approximately 7 days. Therefore, along with the considerable reduction in postoperative pain, the use of sucralfate ointment remarkably increases the rate of epithelialisation.
CONFLICT OF INTEREST
The authors declare no conflicts of interest. This investigation does not have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work.
ACKNOWLEDGEMENTS
The source of funding for this research is the Vice Chancellor for Research, Birjand University of Medical Sciences.
Vejdan AK, Khosravi M, Amirian Z, et al. Evaluation of the efficacy of topical sucralfate on healing haemorrhoidectomy incision wounds and reducing pain severity: A randomised clinical trial. Int Wound J. 2020;17:1047–1051. 10.1111/iwj.13369
This investigation has been carried out in Imam Reza Hospital, Department of General Surgery at Birjand University of Medical Sciences.
Funding information Birjand University of Medical Sciences
REFERENCES
- 1. Khanna R, Khanna S, Bhadani S, Singh S, Khanna AK. Comparison of Ligasure hemorrhoidectomy with conventional Ferguson's hemorrhoidectomy. Indian J Surg. 2010;72(4):294‐297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Ferguson JA, Heaton JR. Closed hemorrhoidectomy. Dis Colon Rectum. 1959;2(2):176‐179. [DOI] [PubMed] [Google Scholar]
- 3. Ala S, Saeedi M, Eshghi F, Rafati M, Hejazi V, Hadianamrei R. Efficacy of 10% sucralfate ointment in the reduction of acute postoperative pain after open hemorrhoidectomy: a prospective, double‐blind, randomized, placebo‐controlled trial. World J Surg. 2013;37(1):233‐238. [DOI] [PubMed] [Google Scholar]
- 4. Brunat G, Pouzeratte Y, Mann C, Didelot JM, Rochon JC, Eledjam JJ. Posterior perineal block with ropivacaine 0.75% for pain control during and after hemorrhoidectomy. Reg Anesth Pain Med. 2003;28(3):228‐232. [DOI] [PubMed] [Google Scholar]
- 5. Simoglou C, Simoglou L, Babalis D, Gimnopoulos D. Milligan—Morgan haemorrhoidectomy—complications. Hellenic J Surg. 2014;86:68‐71. [Google Scholar]
- 6. Mirani AJ, Maroof SM, Raza A, Anwar MA, Suleman S, Kamal A. The role of 10% sucralfate ointment in the reduction of acute postoperative pain aft er open hemorrhoidectomy—Introduction. Pak J Surg. 2015;31(3):153‐157. [Google Scholar]
- 7. Margolis AJ. Martindale: the complete drug reference. West J Med. 1988;148(1):104. [Google Scholar]
- 8. Hayashi AH, Lau HYC, Gillis DA. Topical sucralfate: effective therapy for the management of resistant peristomal and perineal excoriation. J Pediatr Surg. 1991;26(11):1279‐1281. [DOI] [PubMed] [Google Scholar]
- 9. Albatanony AA. Sucralfate ointment reduces pain and improves healing following haemorrhoidectomy: a prospective, randomized, controlled and double‐blinded study. Egypt J Surg. 2016;35(2):102. [Google Scholar]
- 10. Shaikh AR, Dalwani AG, Soomro N. An evaluation of Milligan‐Morgan and Ferguson procedures for haemorrhoidectomy at Liaquat University Hospital Jamshoro, Hyderabad, Pakistan. Pak J Med Sci. 2012;29(1):122‐127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Hughes ESR, Cuthbertson AM. Haemorrhoids. In: ESR H, ed. Anorectal Surgery. London, UK: Chapman Hall; 1989:154‐186. [Google Scholar]
- 12. Hosch SB, Knoefel WT, Pichlmeier U. Surgical treatment of piles: prospective, randomized study of Parks vs. Milligan‐Morgan hemorrhoidectomy. Dis Colon rectum. 1998;41(2):159‐164. [DOI] [PubMed] [Google Scholar]
- 13. Folkman J, Szabo S, Shing Y. Sucralfate affinity for fibro‐blast growth factor. J Cell Biol. 1990;111:223A. [Google Scholar]
- 14. Alvandipour M, Ala S, Tavakoli H, Yazdani Charati J, Shiva A. Efficacy of 10% sucralfate ointment after anal fistulotomy: a prospective, double‐blind, randomized, placebo‐controlled trial. Int J Surg. 2016;36(2016):13‐17. 10.1016/j.ijsu.2016.10.017. [DOI] [PubMed] [Google Scholar]
- 15. Alpsoy E, Er H, Durusoy C, Yilmaz E. The use of sucralfate suspension in the treatment of oral and genital ulceration of Behçetdisease: a randomized, placebo‐controlled, double‐blind study. Arch Dermatol. 1999;135:529, 532. [DOI] [PubMed] [Google Scholar]
- 16. Masuelli L, Tumino G, Turriziani M, Modesti A, Bei R. Topical use of sucralfate in epithelial wound healing: clinical evidences and molecular mechanisms of action. Recent Pat Inflamm Allergy Drug Discov. 2010;4(1):25‐36. [DOI] [PubMed] [Google Scholar]
- 17. Gupta PJ, Heda PS, Kalaskar S, Tamaskar VP. Topical sucralfate decreases pain after hemorrhoidectomy and improves healing: Arandomized, blinded, controlled study. Dis Colon Rectum. 2008;51:231, 234. [DOI] [PubMed] [Google Scholar]