Comparison of internal sphincterotomy with topical diltiazem for post-hemorrhoidectomy pain relief: A prospective randomized trialA Chauhan1, S Tiwari1, VK Mishra2, PK Bhatia1
1 Department of Oncosurgery, Army Hospital (R and R), Delhi Cantt, Delhi 110 010, India
2 Department of Surgery, Base Hospital, Delhi Cantt, Delhi, India
Aim: To assess the efficacy of internal sphincterotomy compared with application of topical 2% Diltiazem ointment after hemorrhoidectomy for pain relief. Settings and Design: Prospective randomized study. Materials and Methods: In an 18-month period, 108 subjects with uncomplicated Grade 3/ 4 hemorrhoids were enrolled in the study and were randomized into two equal groups: Subjects in Group A underwent internal sphincterotomy at time of primary surgery while those in Group B received 1 g of 2% Diltiazem ointment locally, thrice daily for seven days. Postoperative pain perception was measured using visual analog score (VAS) and on the basis of number of analgesic tablets (Tab tramadol 50 mg) required in each group. Time to discharge, time to return to work and incidence of complications measured and compared. Statistical Analysis Used: Statistical techniques applied were Student T test, Chi-square and Fisher's Exact Test. Results: There were 102 analyzable subjects (Group A: 50 and Group B: 52). The mean VAS score was significantly less in the internal sphincterotomy group from the fourth postoperative day onwards compared to topical Diltiazem (2.23 vs. 3.72; P =0.031). Similarly, the mean requirement of analgesic tablets [10.54 vs. 15.40; P =0.01] was much lower in Group A. There was no significant difference in terms of time to discharge and time to return to work between the two groups. The incidence of complications was more with the internal sphincterotomy group (11.5% vs. 3 %; P =0.488). Conclusions: In patients undergoing hemorrhoidectomy, addition of surgical internal sphincterotomy results in lesser pain in the postoperative period as compared to those receiving topical application of Diltiazem.
Keywords: Chemical sphincterotomy, hemorrhoidectomy, internal sphincterotomy, pain relief, topical Diltiazem
Pain is almost a constant feature after hemorrhoidectomy, which makes patients defer seeking care for prolapsing, bleeding, and uncomfortable piles.  Different methods used for pain reduction include performing internal sphincterotomy (IS), , or chemical sphincterotomy. , It is well known that the procedure of surgical sphincterotomy carries a small but significant risk of postoperative complications; the most significant among these being the risk of developing fecal incontinence. Given the contradictory results obtained in various studies, a study was instituted to evaluate the efficacy in postoperative pain reduction of topical Diltiazem as compared to lateral internal sphincterotomy when used as an adjunct to Milligan Morgan hemorrhoidectomy.
Study design: The study was a single-center, prospective, randomized trial which was conducted over an 18-month period from July 2005.
Patient selection: Consecutive newly diagnosed patients with hemorrhoids were screened in the Outpatient Department (OPD) for the purpose of enrollment in the study. Those with Grade 3 or Grade 4 hemorrhoids, were planned for open hemorrhoidectomy and were included in the study. Subjects with history of previous anal surgery, presence of additional anal/ perianal disease (e.g. fistula-in-ano, perianal abscess, anal fissure, painful thrombosed hemorrhoids), those unwilling for surgery or ensuring follow-up after discharge, those with history of ischemic heart disease, severe hypertension or orthostatic hypotension; those with current calcium channel blockers use or known to have had side-effect from the use of calcium channel blockers in the past were excluded from the study. Pregnant individuals were also not included in the study.
Methodology: The study was undertaken after obtaining institutional ethics committee approval and subjects were enrolled only after obtaining informed consent from the subjects. A sample size of 50 in each arm was judged to be appropriate on the basis of a power analysis. The study was powered to detect a difference of mean visual analog (VAS) score of 25% between the two groups. The eligible subjects were randomized into two groups (Group A: hemorrhoidectomy plus sphinctorotomy plus placebo cream, Group B: hemorrhoidectomy plus topical Diltiazem) of 54 cases each, using a random number generator. They were blinded to respective treatment arms by an individual who was not involved in the subsequent therapeutic process. The surgery was conducted by a team of specialist surgeons who were blinded to the group allocation and were subsequently not involved in postoperative assessment.
Per operative procedure: All patients underwent the standard Milligan Morgan technique of open hemorrhoidectomy under caudal/spinal block anesthesia. The patients randomized to the IS group underwent an additional procedure of internal sphincterotomy. The internal sphincter was divided up to the dentate line and this was done through one of the hemorrhoidectomy wounds. Meticulous hemostasis was ensured and no intra-anal packing was done.
For the patients randomized to the Diltiazem group, the first dose of 1 g of 2% Diltiazem ointment was applied by the surgeon at completion of the procedure.
Postoperative care : All patients were nursed in wards thereafter. The patients in the Diltiazem group were provided with a dose regulator (measuring spoon), which allowed only 1 g of ointment to be applied at one time. The patient was instructed to apply the ointment himself/herself to the perianal region three times a day for the next seven days .This was done under supervision of nursing staff to ensure, patient learnt the correct technique and hence was able to ensure correct dosage placement. The patient who had undergone IS as an additional procedure were provided with a placebo cream to be applied similarly.
Postoperative analgesia was in the form of Tablet Tramadol 50 mg. Analgesic tablets were dispensed strictly on demand by patient. The patient was allowed full oral feed six hours after surgery. They were advised Sitz bath four times daily and stool softener (Syrup Cremaffin, 2 tsp thrice daily). Postoperative pain perception was measured using visual analog score (VAS).  Patients were instructed about how to record pain score in the VAS sheets provided and then discharged as per their convenience .They were advised to report to OPD routinely at weekly intervals for a period of one month or earlier if they experienced any symptoms suggestive of complications.
Data collection: Postoperative assessment, follow-up and data collection was done by an independent surgical resident who was blinded to group allocation and procedure performed.
Assessment for pain was done by using a VAS card. Requirement of analgesia was assessed by calculating the total number of analgesic tablets consumed by patient during observation period. The total numbers of days to discharge and subsequently return to work were noted. At each OPD visit, inquiry was made for symptoms which would suggest complications. Wexner scoring system  was used to evaluate postoperative incontinence. At the end of the observation period, patient indicated his cumulative satisfaction level on a scale of 0 to 10. Data thus collected was recorded as per a preset proforma.
Statistical analysis: Data was entered in Microsoft Excel format 2000 and was analyzed by using SPSS Version 10. Comparison and analysis between VAS, in two groups, on various days were done by using Student T test. Statistical techniques applied were Chi-square and Fisher's Exact Test. To see the change over a period of time, two-way analysis of variance (Repeated Measure Analysis) followed by Port-Hoch (Multiple range test) was done. P value less than 0.05 was considered as significant.
A total of 108 eligible patients were recruited in the study and they were randomized into two groups of 54 cases each. Group A were designated for internal sphincterotomy while Group B for topical 2% Diltiazem. Four cases from Group A and two cases from Group B were subsequently lost to follow-up. The remaining patients were available and data was analyzed. The flowchart of the trial is summarized in [Figure 1].
The two groups were evenly matched as per age and gender distribution as well as grade of hemorrhoids seen [Table 1]. Comparison of mean VAS scores day-wise between the two groups shows that there was not much difference between the two groups up to the third postoperative day. Thereafter, VAS scores were significantly lower in Group A [Table 2]. The mean number of analgesic tablets required by Group A was 10.54+1.15; while that in Group B was 15.40+ 1.73. This difference was statistically significant ( P value= 0.01). Although the patients of Group A appeared to request for discharge earlier and returned to work earlier than those in Group B, these differences were not statistically significant [Table 3]. The incidence of postoperative complications was more in Group A (6/52, 11.5%) compared to that in Group B (3/50, 3 %), however, this difference was not significant ( P = 0.488; [Table 4]). The overall satisfaction score was significantly higher in Group A (7.18+/- 0.62 in Group A vs. 5.34+/-0.93 in Group B, P =0.01).
Surgical hemorrhoidectomy is currently the most popular treatment for patients with third and the fourth degree hemorrhoids.  The exact cause of postoperative pain after hemorrhoidectomy has not been defined yet, but hypertonia of internal sphincter is widely believed to be the cause of postoperative pain after hemorrhoidectomy. Recent anorectal manometric studies have shown that internal sphincter spasm is present even before surgery in patients with hemorrhoids.  Much of the information concerning pain control after anorectal procedures has been acquired in the treatment of anal fissures. Eisenhammer  was the first to propagate the idea that post-hemorrhoidectomy pain is due to spasm of the internal sphincter and described that its division through one of the hemorrhoid wounds is certainly an effective way to lessen postoperative pain. However, this idea of his did not become popular.  More recently some studies have reinvestigated this concept. Several investigators , have concluded that sphincterotomy significantly improves the postoperative course after hemorrhoidectomy and that the procedure is safe. As IS is known to lead to permanent minor impairment of continence leading to incontinence of flatus, mucus, or occasionally stool, other authors have espoused the concept of chemical sphincterotomy with topical nitrates and calcium channel blockers. Much of the role of chemical sphincterotomy has been learnt from experience of treating chronic anal fissures. ,,, Amongst the agents employed for "chemical sphincterotomy" several investigators tend to favor use of calcium channel blockers over topical nitrates citing the much lower incidence of complications in the former. , Topical Diltiazem blocks calcium uptake in the myocytes thereby decreasing contraction of internal anal sphincter. It has been demonstrated to have significant healing rates for chronic anal fissures by reducing the anal sphincter pressure. ,, Our study demonstrated that pain relief was better in patients subjected to IS than topical Diltiazem although this was more evident from the fourth postoperative day. We must also recognize the fact that while lateral IS would be a uniform technique across patients, the same cannot be said about the effect of Diltiazem. Local absorption of Diltiazem is not only proportional to the amount applied, but also to factors such as skin thickness and quantum of tissue inflammation. For this reason, the presence of perianal wounds after hemorrhoidectomy may significantly affect the kinetics of Diltiazem absorption and its activity may be reduced by tachyphylaxis.  This may be one of the important factors explaining inferior pain relief obtained in this group.
The study may be criticized as it relies on reporting of VAS scores by the patient. It is accepted that VAS attempts to equate subjective feedback with objective data and is thus subject to valid criticism. In our series, pain perception was also measured indirectly by recording the number of Tramadol tablets demanded by the patient.
It is interesting to note that, contrary to expectations, this better pain relief did not translate into actual earlier discharge to home or earlier return to work in the IS group. It leads to a conjecture on our part that perhaps there are intangible factors such as a psychological component of having undergone a "major" surgery, which play in a patient's decisions to seek discharge and return to work. Another criticism can be that the pain relief documented in the study has not been corroborated with objective manometric findings before and after surgery. It is known that resting anal pressure is elevated in symptomatic hemorrhoids and hemorrhoidectomy leads to decrease of same. , Hence it would be expected that there would be correlation between this and pain relief. While this remains a valid observation, we opine that this was a study done on purely clinical parameters which can be readily replicated and revalidated. As the primary effort is towards pain relief after hemorrhoidectomy, using pain assessment tools as measure of primary endpoint is valid enough.
It can further be argued that the study has poor external validity i.e. as hemorrhoidectomy is done quite often as a day-care procedure unlike our study where we admitted the patients, the results obtained in this study may not be replicated. Ours is a large urban tertiary referral center which caters to gentry varied in socioeconomic and educational levels. We admitted the patients so as to ensure uniformity in carrying out of instructions and ensure there is no bias. The study was also limited by the fact that a "per protocol" and not "intent-to-treat (ITT) analysis was performed.
The dataset was analyzed by Student T test as the sample size was relatively small and the test of normality indicates that the two samples being compared do not come from widely differently shaped distributions. Moreover, Levene's Test for Equality of Variances confirms that the two samples are not of unequal variance.
Overall incidence of complications was higher in the IS group and the complication profile was different between the two groups. Incontinence to flatus was found in three patients of this group though the patients did not report them so severe as to be a nuisance. Indeed, studies suggest that the fear of incontinence after internal sphincterotomy may be overrated.  At the same time it must be acknowledged that this study may not reflect the true incidence of anal incontinence as the period of follow-up was rather short (seven days). Incontinence may be found in the late perioperative period too. On other hand, Diltiazem taken orally results in systemic and coronary vasodilatation resulting in most of its reported side-effects including flushing, dizziness and headache. However, applied topically, it appears to be safe. In our series, out of the 50 cases in Group B, only one complained of headache. It may be pointed out that the statistical analysis was performed on sum of all complications in each group and not each complication individually. This was so because incidence of each complication was too less within the studied population to be analyzed meaningfully if done so separately.
Overall satisfaction level was seen to be more in the IS group. This can be attributed to better pain relief obtained in this group. It may be questioned whether addition of sphincterotomy (surgical or chemical) is actually better than hemorrhoidectomy alone. Indeed Mathias et al. ,  conducted a randomized prospective study in 33 patients wherein hemorrhoidectomy, plus LIS was compared with hemorrhoidectomy alone. They found no difference in pain scores and analgesic requirements between the two groups. They suggested that either internal sphincter spasm is not the dominating cause of pain in the postoperative scenario or else routine analgesia is sufficient to control the pain. Similar thoughts are echoed by Khubchandani.  In his series of 42 patients, he compared hemorrhoidectomy alone with hemorrhoidectomy plus internal sphincterotomy. He did not find any benefit in pain perception at four hours postoperative, at first bowel motion and at four days interval. However, in both the aforementioned studies, the observation periods were much shorter, three days in the former and four days in the latter. In the present study the difference in pain relief appears significant fourth day postoperative onwards. Our results are in agreement with those by Amorotti et al . 
The present study taken in consonance with previous works indeed suggests a beneficial effect of surgical internal sphincterotomy more than chemical sphincterotomy as an adjunct procedure to standard hemorrhoidectomy and that the benefit of this procedure outweighs the perceived risk of complications.
[Table 1], [Table 2], [Table 3], [Table 4]