Laxatives and topical treatments for hemorrhoids.
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to evaluate the efficacy of laxatives and topical treatments in improving the symptoms derived from symptomatic hemorrhoids
Background
Hemorrhoids are a normal anatomic, cushion‐like, structure, and their existence alone, does not constitute disease. Only symptomatic hemorrhoids can be regarded as a medical condition. This physiologic 'padding' is thought to play a key role in maintaining anal continence while also providing important sensory information that enables the differentiation between liquid, solid and gas (Beck 1998) Hemorrhoids are generally divided into internal and external hemorrhoids being the dentate line their anatomical border. Internal hemorrhoids are also divided into four categories depending on the grade of prolapse (first‐grade: Protrude into the anal canal but do not prolapse, second‐grade: Prolapse but spontaneously reduce, third‐grade: Prolapse and require manual reduction, and fourth‐grade: Irreducible prolapse.)
Hemorrhoids are a very common medical condition, its prevalence ranging from 4.4% in the general population, to 36.4% in general practice (Abramowitz 2001), however, only a third of patients do seek medical help (Johanson 1990). The pathophysiology is still no clearly understood but structural and/or vascular changes may be involved (Beck 1998) and have been unconsistently associated with chronic straining (Johanson 1994). They are also common during pregnancy (Beck 1998).
Symptomatic hemorrhoids are usually bothersome for most patients but are considered a benign condition. They tend become a chronic disease with very variable symptomatic or asymptomatic periods.The most common symptoms of hemorrhoids are bleeding and prolapse and, less frequently, they may also include discomfort, pain, soiling or mucoid discharge, which may cause local irritation and pruritus (itching). Internal hemorrhoids are usually painless and it is bleeding or prolapse what generally makes the patient come to the physician. This bleeding is usually described as bright red spotting on the toilet tissue or dripping in the toilet bowl and normally occurs at the end of defecation, separately from the stool. External hemorrhoids may be asymptomatic, associated with discomfort or with acute extreme pain in the event of a local thrombosis (formation of a clot). However, all these symptoms are not specific related to hemorrhoids and can only be regarded as such after the clinical examination justifies for example a bleeding episode. A minimal physical examination is therefore needed (anorectal examination, digital palpation and anuscopy in some cases) (Alonso‐Coello 2003, Alonso 2002).
The initial approach, usually for first and second‐grade hemorrhoids, is usually carried out in primary care and for most people is the only treatment they will ever need. The first step is to increase the amount of fiber and water intake in the diet, or adding fiber supplements. Some other first line options that are usually regarded are avoiding certain foods, topical therapies (cold water, creams, e.g.). Although the role of certain foods in the pathogenesis of hemorrhoids or their acute exacerbation is accepted empirically, it has not yet been proved. There is no firm evidence to date that increasing physical exercise or improving local hygiene have a beneficial effect. Phlebotonics are sometimes also used, mainly during acute exacerbations (Lyseng‐William. 2003). The effect of phlebotonics will be dealt with in another systematic review (Alonso 2003).
Non‐operative and surgical interventions are then considered in patients who do not improve with these initial measures (Abramowitz 2001, Brisinda 2000). All non‐operative and surgical procedures work by fixing the sliding hemorrhoidal tissue back onto the muscle wall. The fixation takes place by either directly promoting tissue fibrosis (eg. sclerotherapy or infrared coagulation) or by tissue destruction with subsequent fibrosis (e.g. hemorrhoidectomy) (Johanson 1992). About 10% of patients will require operative treatment (hemorrhoidectomy) either due to the severity of the disease or due to failure of the above techniques (Bleday 1992). This procedure is generally regarded as a second line option because patients find it generally more painful.
Since the development of hemorrhoids seems partly related to prolonged straining, the main purpose of lifestyle measures and medical treatment is to minimize this. Generally the initial approach is to increase the amount of water and fiber in the diet, or prescribe a laxative especially for first and second‐degree hemorrhoids. Low fluid intake has generally been cited as a risk factor for constipation (Petticrew 2001) but the effectiveness of increased fluid intake as a treatment for constipation remains largely unknown at present.
Dietary fiber intake has been positively associated with increases in bowel movement frequency and fecal mass and symptoms (Bennett 1996, Spiller 1994) and a meta‐analysis of the effects of wheat bran showed an increase in stool weight and decreased transit time. Several clinical trials have studied the effect of a high‐fiber diet or fiber supplements compared with placebo, in improving pain, bleeding and prolapse of patients with hemorrhoids (Perez‐Miranda 1996, Moesgaard 1982). These findings apply mostly to first and second‐degree hemorrhoids. Other types of laxatives include; stimulant laxatives, osmotic agents and faecal softeners. In several systematic reviews laxatives have proved that they all work slightly better than placebo (Kenny 2001, Petticrew 2001, Tramonte 1997) or haven't found any significant differences (Jones 2002). All these authours acknowledge the limitations of the included studies (poor methodology) and the lack of sound head to head comparisons.
Although there seems to be no rigorous evidence to support the use of topical therapies, physical (sitz baths, ice, etc.) or pharmacological (anesthetics, phlebotonics, glucocorticoids, etc.) they are very popular and nevertheless many patients report some grade of empirical benefit with their use, especially with glucocorticoids and anesthetics (Alonso‐Coello 2003). This is the case with popular topical soothing agents, which often in combination with corticoids and/or anesthetics are currently on the market (creams, enemas, e.g.). However most studies have been of low methodological quality, not placebo controlled and addressed heterogeneous preparations with multiple associated components. The true benefits and efficacy of these treatments are still not clear and there is concern about the adverse local effects they may produce/provoke (allergy, sensitization of skin ) being generally recommended for short periods of time (seven or ten days) (Abramowitz 2001)
The reason to consider these two treatment options in a single review is due to the fact that most patients are generally treated with both and they are usually regarded as the first general approach in clinical practice to symptomatic hemorrhoids, especially in the first and second degree episodes. However there is uncertainty about their effectiveness. To our knowledge the role of these two treatment options, for the treatment of hemorrhoids have not been reviewed systematically yet, therefore there is a need to undertake a systematic review on these two initial treatment options.
Objectives
The objective of this review is to evaluate the efficacy of laxatives and topical treatments in improving the symptoms derived from symptomatic hemorrhoids
Methods
Criteria for considering studies for this review
Types of studies
All published and unpublished parallel group double blind randomised controlled trials (RCTs) will be eligible for inclusion in the review.
The first phase only of cross over studies will also be included. Randomised controlled trials published as abstracts or as letters will be included in the primary analysis. However, in order to explore the potential bias resulting from their inclusion, a secondary sensitivity analysis will be conducted. Quasi‐random studies will be excluded.
Types of participants
1)Patients of both gender and all ages receiving fiber and/or topical treatments for first, second, third and fourth‐grade haemorrhoids symptomatic or asymptomatic will be eligible.
2)Pregnant women or women with hemorrhoids after delivery will also be considered if any studies are found.
3)Patients of both gender and all ages receiving fiber and/or topical treatments with thrombosed hemorrhoids.
Types of interventions
Comparisons against placebo and between any of the treatments mentioned below will be included:
LAXATIVES
1. Fiber administered orally. Fiber will include:
‐ A high fiber diet
‐ Bulking agents: bran, ispaghula, psyllium, etc.
3. Stimulant laxatives: senna, bisacodyl, etc.
4. Faecal softeners: liquid paraffin, seed oils, etc.
5. Osmotic agents: lactulose, magnesium hydroxide, sorbitol, lactitol, etc.
6. Combinations of any of the above
TOPICAL THERAPIES (physical or pharmacological):
‐Physical: cold or hot water, ice, local hygiene, etc.
‐Pharmacological: delivered as creams, soothing agents, enemas and containing any of the following:
1‐ Anesthetics: lidocaine, procaine, etc
2‐Corticosteroids: prednisone, metilprednisolone, etc.
3‐Phlebotonics will include:
Natural products
‐flavonoids: rutosides (troxerutin, buckwheat herb extract, ruscus aculeatus), diosmine, hidrosmin, ginko biloba
‐saponosides: escin (horse chestnut seed extract)
Synthetic products: calcium dobesilate, naftazone, aminaftone, chromocarbe
Others:iquinosa, flunarizine, sulfomucopoly‐saccharide
4‐Combinations of any of the above products
5‐Others: nifedipine, etc.
Types of outcome measures
Main outcome measures to be assessed include symptom control, new episodes of symptomatic hemorrhoids, thrombosed hemorrhoids, degree of prolapse and adverse events. Authors will be contacted for more details if any of the main outcome measures are not included in the original paper.
Adverse events will be assessed as individual categories and overall percentage of incidence will be used as summary measure. Re‐treatment rates especially need for subsequent operative treatment for the individual techniques will be sought and reported as number of incidents.
Patient satisfaction will be assessed when possible from the original publication. If needed authors will be contacted for additional information. The longest follow‐up reported will be used for the purpose of this review.
Search methods for identification of studies
The search strategy advocated by Cochrane Colorectal Cancer Group (CCCG) will be adopted.
The following strategy will be used to search MEDLINE (Ovid) and will be adapted for EMBASE and CCTR with the addition of a randomised control trial filter for MEDLINE (Dickersin 1994) and EMBASE (Lefebvre 1996).
#1. exp hemorrhoid
#2. hemorrhoid*
#3. haemorrhoid*
#4. hemorroid*
#5. haemorroid*
#6. or/1‐5
#7. Agar
#8. Bisacodyl
#9. Bran
#10. Bulk
#11.Casanthranol
#12. Cascara
#13. Castor oil
#14. Cellulose
#15. Dietary fiber (eliminar y dejar Fiber)
#16. Dioctyl sulfosuccinates
#17. Emodin
#18. Enema
#19. Fe$cal ADJ softener*
#20. Fiber
#21. Fruit
#22. Fruit adj5 juice*
#23. Glucitol
#24. Glycerin
#25. Glycerol
#26. Guar
#27. Laxative*
#28. Lignine
#29. Liquid adj5 paraffin
#30. Magnesium compounds
#31. Magnesium oxide
#32. Methyl‐cellulose
#33. Mineral oil
#34. Oxyphenisatin acetate
#35. Paraffin
#36. Phenolphthaleins
#37. Phosphates
#38. Plantago ovata
#39. Polyethylene glycols
#40. Prune*
#41. Psyllium
#42. Purgative*
#43. Rhubarb
#44. Roughage
#45. Senna
#46. Sorbitol
#47. Stool adj5 softener*
#48. Tragacanth
#49. or/7‐48
#50. Cold
#51. Cryo*
#52. Fluid*
#53. Hot
#54. Hydratation
#55. Hydration
#56. Ice
#57. Local
#58. Water
#59. Local hygiene
#60. or/50‐59
#60. Lidocaine
#61. Procaine
#62. Prilocaine
#63. Corticosteroids
#64. Metilprednisolone
#65. Hydroxycorticosteroids
#66. Corticoids
#67. Budesonide
#68. Hydrocortisone
#69. or/60‐68
#70. Nifedipine
#71. phlebotonic$.ti,ab
#72. venotonic$.ti,ab
#73. exp Bioflavonoids
#74. Calcium Dobesilate
#75. (dobesilate$ OR daflon OR aminaphton$ OR naphto$ OR doxium OR escin OR
rutoside$ OR diosmin).ti,ab
#76. Escin
#77. Polycresulene
#78. or/70‐77
#79. #49 or #60 or #69 or #78
#80. #79 and #6
The Cochrane Controlled Trials Register, Medline, EMBASE, CINAHL, AMED, SIGLE electronic databases will be explored using broad search strategies to identify all randomised controlled trials evaluating the use of fiber and/or topical therapies for hemorrhoids. All searches will be run from the earliest date available (1966 for MEDLINE, 1988 for EMBASE, and 1982 for CINAHL). A final search of MEDLINE and EMBASE will be undertaken three months before publication. All languages and indexed journals will be included and retrieved. Reference lists from trials selected by electronic searching will be hand searched to identify any other relevant trials.
Experts in the field of anorectal diseases known to the review team and or the Colorectal Cancer Group will be contacted. They will be requested to supply any information about trials that they either knew about or were conducting. The editors of general medical, gastroenterology and general surgery journals will be contacted for information on any papers on fiber and/or topical and hemorrhoids undergoing peer review. Pharmaceutical companies will also contacted for any data on trials that had been published or were unpublished and in their archives.
On‐going trials will be searched for on the following databases:
‐Meta Register of Controlled Trials (mRCT) http://www.controlled‐trials.com
‐US NIH register http://clinicaltrials.gov
‐Register of the Center for Clinical Trials and Evidence‐Based Healthcare http://trialscentral.org
Data collection and analysis
1) Selection Of Studies: One reviewer will exclude papers from the initial searches unrelated to hemorrhoids in humans. These decisions will be based on account of the title or abstract if available. A second reviewer independently will check a sample of 30% of the studies excluded of this selection process. Afterwards, two reviewers will asses the remaining results for the potentially relevant studies for the review. Disagreements will be reviewed, and a third reviewer will be consulted if they cannot be resolved.
Only afterwards inclusion decisions will be made independently by two reviewers according to the pre‐stated eligibility criteria, and recorded on a specially developed form. Disagreements will be reviewed, and a third reviewer will be consulted if they cannot be resolved. We will retrieve the full articles for all the potentially relevant trials and scrutinize each trial report for multiple publications from the same data. The trials that are relevant for ther review but are classified as not eligible will be displayed in a table together with the reason for their exclusion.
2) Assessment of Study Quality:
Study internal validity will be assessed by two reviewers independently using a pre‐designed form. Disagreements will be reviewed, and a third reviewer will be consulted if they cannot be resolved. The results of the internal validity for the included studies will be displayed on a table.Only trials which describe the word 'random, randomly, or randomised' in their trial will be considered in this review and assessed independently by two reviewers for quality according to four characteristics (Clarke 2002).
‐Generation of the allocation schedule: truly random, systematic or not stated/unclear.
Computer generated random numbers, coin toss, shuffles, etc will be considered as truly random, allocation according to birth‐date, patient number, etc as quasi‐random, whilst alternate allocation and deterministic methods will be classified as systematic.
‐Concealment of the treatment allocation: adequate, inadequate and unclear (Juni 2001).
If trialists are unaware of each participant's allocation when they are recruited, the allocation is said to be adequately concealed. Methods such as central randomisation systems or serially numbered sealed opaque envelopes fit this criteria. If the trialist may be aware of allocations at recruitment, as when the participant's birth‐date or patient number is used for allocation, the allocation is inadequate.
‐Implementation of masking: patient masked, clinician masked and outcome assessor masked.
When a placebo is used it will be assumed that the participants are masked to their treatment allocation,
‐Completeness of follow‐up and intention to treat analysis
(drop‐outs and missing data rates by group).
Quasi‐random studies and trials with an inadequate allocation will be excluded.
3) Data Extraction: Data will be extracted and recorded onto specially developed forms. Extraction will be undertaken by two reviewers. Disagreements will be reviewed, and a third reviewer will be consulted if they cannot be resolved. Data entry into RevMan will also be double‐checked. If data from the trials report are insufficient, we will contact the authors for additional information. The following characteristics will be recorded for each trial:
‐Details of the participants including demographic characteristics, source of recruitment, criteria for diagnosis, and symptoms on presentation. Trials will be categorised according to the most prevalent type of hemorrhoids: first, second, third or fourth‐grade hemorrhoids if possible,
‐Details of the experimental and control interventions including intervention type, names, dosages and schedules where appropriate,
‐The prevalence of individual symptoms before and after the intervention, hemorrhoid symptom scores and global assessments of symptoms. Where measurement scales are used it will be noted whether or not they were standard scales and whether they had been validated.
Where possible we will extract the data to performa an intention‐to‐treat analysis. If the numbers randomized and the numbers analysed are inconsistent, we will calculate the percentage loss‐to‐follow‐up and report this information in an additional table.
4) Data Management:
We will analyse the data using Review Manager (Version 4.1). Data Synthesis for binary outcomes, such as the presence or absence of symptoms, the impact of the intervention will be expressed as relative risks and relative risk reductions (RRR) (1‐relative risk) together with 95% confidence intervals. NNT will also be calculated if appropiate.
For scale‐based outcomes means and standard deviations will be used to summarise the values in each group. Symptom scores may be pooled as continuous variables, either using weighted means, or standardised means, or converted to a binary scale by dividing the patients into symptomatic and asymptomatic groups on the basis of their score. Most trials either do not report symptoms on the same scale, or do not report the symptom score at all. Some scores are based on symptom frequency, others on both frequency and severity. To overcome this problem, we will contact the authors if needed and ask them to provide figures for a standardised binary conversion of their scale provided the scale used sufficient values (roughly more than 10). Such outcomes will be analysed for the presence of skew
Where it is appropriate to pool data we in intend to use a random effects analysis if significant (P <0.1) heterogeneity is detected in the data. We do not intend to combine results of trials with different comparator treatments or drugs. Reasons for heterogeneity will be explored and trials will be categorised into the following predefined subgroups:
‐Trials specifically dealing with thrombosed hemorrhoids
‐Trials specifically dealing with pregnant women or episodes in women just after delivery
‐Methodological quality (generation of the allocation schedule, concealment of the treatment allocation, implementation of masking and completeness of follow‐up)
‐Multi‐centre versus single centre trials
‐The length of follow‐up
‐The use of validated questionnaires
We will consider publication bias using a funnel plot. It is acknowledge that funnel plot asymetry could be caused by publication bias, quality, or heterogenety.Assessments of quality of life and adverse events will be noted.
