Study of safety and efficacy of local application of Apamarga Kshar ointment in the management of Abhyantar Gudarsh with special reference to internal haemorrhoids. : Randomized Controlled Clinical Study

Hemorrhoids are a very common anorectal condition defined as the symptomaticenlargement and distal displacement of the normal analcushions. Haemorrhoids, also called piles, are swollen veins in your anusand lower rectum; similar to varicose veins. Hemorrhoids have a number ofcauses, although often the cause is unknown. They may result fromstraining during bowel movements or from the increased pressure on theseveins during pregnancy. Hemorrhoids may be located inside the rectum(internal hemorrhoids), or they may develop under the skin around the anus(external hemorrhoids). Worldwide, the overall prevalence of hemorrhoidsin the general population is estimated to be 4.4%. It is estimated thatmore than 50% of the population over 50 years of age have experiencedhemorrhoid problems13. It is very difficult to live with symptoms andcomplication of internal haemorrhoids. Anaemia due to per rectal bleedingsecondary to haemorrhoids is one of important reason for blood transfusion. Multiplefactors have been claimed to be the etiologies ofhemorrhoidal development, including constipation and prolonged straining.The abnormal dilatation and distortion of the vascular channel, togetherwith destructive changes in the supporting connective tissue within theanal cushion, is a paramount finding of hemorrhoidal disease.

Today’s lifestyle ischanged; most of the people are not perfect in their food habits. Theyhave bad food habits like irregular intake of food, eating of fried foods,excessive use of chilies and spices in food, etc. which is causativefor haemorrhoids. Therapeutic treatment of hemorrhoids ranges fromdietary and lifestyle modification to radical surgery, depending on degreeand severity of symptoms. Those have their advantages and limitations.Variety of topical treatments is available in market. The primaryobjective of most topical treatment aims to control the symptoms ratherthan to cure the disease. Thus, other therapeutic treatments could be subsequentlyrequired. A number of topical preparations are available including creamsand suppositories. These topical medications can contain variousingredients such as local anesthesia, corticosteroids, antibiotics andanti-inflammatory drugs4.

No radical topicaltreatment is not available. Hence radical non surgical treatment in formof topical ointment is need of time. After review of literature it wasobserved that such management of abhyantar Gudarsh is mentioned in ancientayurvedic Samhita. Acording to Sushruta management of Abhynatar Gudarsh isof four types. Aushadhi Chikitsa, Ksharkarma, Agnikarma and Shastrakarma.Amongst that Ksharkarma is more effective non invasivemethod. Although effective but traditional Pratisaraniya Ksharkarma6 ismore complex and tedious process. So modification in it is requirement ofcurrent era.

Kshar Ointment ismodification of Kshar Pratisaran. Previous study with Yava Kshar ointmentwas done. Siktha taila is previously used as a base for Kshar ointmentpreparation is proven safe and effective as a base.10 This showed encouragingresults. But Yava Kshar is difficult to prepare and alsoexpensive. Apamarga Kshar is used as Pratisaraniya Kshar at many placesand is very effective7,8,9,10. Hence Apamarga Kshar is used in currentstudy in place of Yava Kshar. Apamarga Kshar ointment which is an ointmentof Apamarga Kshar with base Siktha taila is modified technique forKsharkarma which will be used in current study.

Current Study is havingnovelty in selection of drug, drug dose and animal study. It is OpenLabeled, Randomized Controlled Phase I/Phase II Clinical Study. ApamargaKshar ointment will be prepared and tested with animal study for itseffectiveness and its dermal safety. Animal Study will be carried out at AnimalHouse of genuine institute. Clinical study will be carried out in twogroups. Observation from both groups will be noted. Analyzed statisticallyand Discussed with conclusion after study.

 Research Question

Whether Apamarga Ksharointment is effective in Abhyantar Arsha Chikitsa to reduce per rectalbleeding and size of internal haemorrhoids?

 Hypothesis

Hypothesis of this PhDthesis will be - Apamarga Kshar ointment applied locally at internalhaemorrhoids once a day for 28 days with laxative ‘Avipattikar Churna’orally is effective in reducing per rectal bleeding and degree of internalhaemorrhoids.

H0 = Apamarga Ksharointment applied locally at internal haemorrhoids once a day for 28 dayswith laxative ‘Avipattikar Churna’ orally is not effective in reducing perrectal bleeding and degree of internal haemorrhoids.

HA = Apamarga Ksharointment applied locally at internal haemorrhoids once a day for 28 dayswith laxative ‘Avipattikar Churna’ orally is effective in reducingper rectal bleeding and degree of internal haemorrhoids.

 Animal Study inference:

Asper histopathological studies and hematological parameters, the applicationof Apamarga kshar ointment is effective in the management ofcroton oil-induced internal hemorrhoids in Wistar rats. It is not having anyadverse effect on histopathology and in relation to hematological parameters.Increase in some lipid profile tests shows that Apamarga kshar ointmentbase was absorbed systemically but it did not have any negative changes onliver function test and kidney function tests. Hence, Apamarga kshar ointmentcan be used in humans for further clinical trials.

 Observation and results

Sexwise distribution of patientsIt was observed that male and female patients were equallydistributed in both group. A number of male patients was more than femalepatients in both groups. There is no significant statistical difference. Malepatients were more than that of female patients. In previous studies, also itwas observed that male patients are more than that of female patients133.However, in larger study it was found that males and females are equallyaffected by haemorrhoids134.

Agewise distribution of patientsMaximum patients in both group was from the age group 31 to45 years and then between 45-60 years. This disease is more common inmiddle-aged people. In previous studies also it was mentioned that About 50% ofpeople would have hemorrhoids at some point in their lives by the age of 50,and hemorrhoids affect 5% of the population on average at any given time.

Per rectal bleedingIt was observed that almost all patients were having eithermoderated or severe per rectal bleeding. When the clinical trial started, bothgroups were having equally distributed patients of per rectal bleeding.Bleeding is most common and important symptom of hemorrhoids, which takespatients to clinicians; hence, all patients were having per rectal bleedingbefore treatment. Per rectal bleeding was reduced with high significance withboth treatments.

Apamarga kshar pratisaran isa trusted and proven treatment in the management of internal hemorrhoids. Itreduces PR bleeding by inflammation, healing, and fibrosis of hemorrhoidalcushion.

Apamarga kshar ointment is used daily afterdefecation. It has all properties of Apamarga kshar,which is useful in reducing per-rectal bleeding after localized application.This action was supposed to be due to Apamarga ksharbyproducing inflammation and fibrosis of hemorrhoidal tissue. Base sikthtaila is having lubricating properties, which help to lubricate andheal of hemorrhoidal cushion and reduce friction and injury to haemorrhoidaltissue while defecating and causing a reduction of per rectal bleeding.

Degree of HemorrhoidsPatients with the degree of hemorrhoids grade II and gradeIII were present in both groups. Both groups are having no statisticaldifference in a baseline. Maximum patients were from grade II and grade III.Many patients ignore symptoms in grade I and in Grade IV surgery is the choiceof treatment.135 Hence, for conservative treatment only gradeII and grade III patients were available and selected as inclusion criteria forstudy.

With both treatments, change in the degree of hemorrhoidswas observed late i.e. after 28 days to 45 days. This change may be observeddue to the healing and fibrosis of hemorrhoidal tissue, which ultimatelyreduces prolapsing mass. Long-term follow-ups and treatment may change thedegree of hemorrhoids in many patients. This needs further prolonged study.Over all treatment was effective with high significance in reduction ofprolapse mass of hemorrhoids and degree of hemorrhoids.

Discharge per analIt was observed that discharge per anal was mild in maximumpatients at the beginning of the study and difference in both group was notsignificant. Hence, both groups were from the same population.

Discharge per anal is maximum and associated with patienthaving 4thgrade hemorrhoid. In the current study, the maximumpatient was from 2nd Grade and 3rd Grade. Hencea maximum number of patients were with mild to nil discharge per anal. Aftertreatment in a group, reduction in per anal discharge was seen in both groups.Overall treatment was effective in treatment of discharge per anal.

FinalOutcome:Primary Outcome:It was observed that all patients from both groups hasimprovement in disease. Per rectal bleeding was totally stopped in 101 (92.66%)and 102 (95.32%) patients in Apamarga kshar pratisaran and Apamarga kshar ointmentgroup respectively. Per rectal bleeding reduced to mild in 8 (7.32%) and 5(4.67%) patients in Apamarga kshar pratisaran and Apamarga kshar ointmentgroup respectively. Discharge per anal totally stopped in 105 (96.33%) and 102(95.32%) patients in Apamarga kshar pratisaran and Apamarga kshar ointmentgroup respectively

Discharge per anal was reduced to mild in 2 (2.75%) and 4(3.74%) patients in Apamarga kshar pratisaran and Apamarga kshar ointmentgroup respectively. Change in degree of hemorrhoids observed in 32(25%) patientstreated with Apamarga kshar pratisaran and26 (21%) patients treated with Apamarga kshar ointment.

All patients who underwent complete treatment have shownimprovement in both groups.

19 (15%) patients from Apamarga kshar ointmentgroup and 17 (13.49%) patients from Apamarga kshar pratisaran groupdropped out as they did not completed treatment protocol.

No complete cure in any patient of both groups was observed.

Secondary Outcome:Nocomplication observed in any groups. Initially local irritation observed insome patients who did not wipe anal region after treatment. However, it wasresolved after 2 to 3 days of taking care about wipe out excessive ointment atanal region.

Conclusion

From results and statistical analysis, it was concluded that

Apamarga kshar ointment applied locally iseffective in reducing C reactive protein significantly as compared to activecontrol. It has histopathological changes indicating reduction in inflammation,healing with fibrosis. It reduces recto anal coefficient after treatment ascompared to active control.

Application of Apamarga kshar ointmentis effective in management of croton oil induced internal hemorrhoids in Wistarrats.

Apamarga kshar ointment wasabsorbed in systemic circulation and showed minimal increase in serumtriglycerides, serum LDL and VLDL cholesterol. However, it did not have anynegative effect with respect to liver function test and Kidney function test ofWistar rats. Hence, Apamarga kshar ointment issafe and not having any acute toxic effect.

Primary Outcome : Apamarga kshar ointmentreduced per rectal bleeding from 3rd day and it was nil in95.66% compared to Apamarga kshar pratisaran, inwhich it was 92.06% patients after 28 days.

Apamarga kshar ointment waseffective in reduction of degree of internal hemorrhoids in few patients but itdid not reduced degree of haemorrhoids in all patients. Long-term treatment maybe effective in reduction of degree of internal hemorrhoids.

Apamarga kshar ointment was effectivein reduction of per anal discharge associated with internal hemorrhoids nil in95.33% compared to Apamarga kshar pratisaran, inwhich it was 96.33% patients after 28 days.

Secondary Outcome : No complications wasobserved with treatment.

Hence, It is concluded that Apamarga kshar ointmentis effective in management of per rectal bleeding, reducing per anal dischargedue to internal hemorrhoids and degree of hemorrhoids up to some extent.

Thus, alternative hypothesis HA i.e. Local application ofApamargaksharointment at internal haemorrhoids once a day for 28 days withlaxative ‘Avipattikar Churna’ orally is effective to reduce perrectal bleeding and gradation of internal haemorrhoids is accepted

 Difficulties in actual work :Local application of Apamarga**kshar ointment is to be done by patient at home. Therefore, applicationof ointment has possible error due to improper technique by patient, notfollowing proper treatment schedule and protocol by patient.

If some part ofointment remains on normal skin then it can cause local irritation andexcoriation. Hence, patient must be advised to wipe out extra ointment, whichis present outside of anus.

Squeezing pressure bypatient can differ much time. Hence, quantity of ointment applied athemorrhoids differs and which can interfere with desired outcome.

Ointment base is sikthtaila, which is combination of Tila taila and beeswax it tends toget harder in consistency during winter. This makes application of ointmentdifficult as ointment come out of tubes difficultly and only after excessivepressure. This problem was tackled by advising patient to keep ointment tube inwarm water before application. Further, by increasing proportion of Tilataila in base sikth taila this problem can be solved.

Use of slit proctoscopeis sometimes painful. While removing proctoscope if slit proctoscope is nothaving complete slit then hemorrhoid gets stuck in lower end of proctoscope andit hurts patient.

If slit is completethen obturator of proctoscope does not fix properly and again it may hurt patientwhile insertion of proctoscope. Hence, procedure should be done very delicatelyand with well-lubricated proctoscope only.

Apamarga kshar**pratisaran need one or two assistant while applying kshar. Oneassistant is required for holding proctoscope and another for providing kshar,Amla dravya and other instruments.

Application of Apamargakshar can be done with spatula. Loss of drug i.e. Apamarga ksharis observed if pratisaran is done with the ear buds or cotton swabs.

Assessment ofper-rectal bleeding, discharge per anal and prolapsed of hemorrhoid duringdefecation is totally dependent on patients response. It is not possible forassessment actually by intervening doctor. This error can cause error in finalinterpretation.

Suggestions

Long-term comparative animalstudy i.e. for full duration of treatment is expected to be done for assessmentof local changes after long-term treatment.

Assessment of changes inlipid profile of animals after long-term treatment and after seasation oftreatment for one month.

Study for longerduration for assessment of complete reduction in degree of hemorrhoids.

Study for changes inlipid profile of patient using Apamarga Kshar Ointment,