594 Postgrad Med J: first published as 10.1136/pgmj.2004.031690 on 2 September 2005. Downloaded from ORIGINAL ARTICLE Comparative study of enema retention and preference in ulcerative colitis J R Ingram, J Rhodes, B K Evans, R G Newcombe, G A O Thomas ............................................................................................................................... Postgrad Med J 2005;81:594–598. doi: 10.1136/pgmj.2004.031690 Background: Therapeutic enemas are often used to treat active colitis but their retention may be limited because of urgency to defecate. Some preparations may be better retained and tolerated than others See end of article for because of their physical properties. authors’ affiliations ....................... Aim: To compare patient preference and retention of four therapeutic enemas, including a nicotine enema, in patients with ulcerative colitis (UC). Correspondence to: Methods: Twenty four patients with active UC received the four trial enemas—corticosteroid, 5-amino Dr G A O Thomas, Department of salicylate (5-ASA), and nicotine liquid enemas and a corticosteroid foam, in a randomised order, taking Gastroenterology, one enema on each of four successive nights. Patients scored them 1 to 4 for ease of administration and University Hospital of retention, degree of abdominal bloating, and for their overall preference. Wales, Heath Park, Cardiff CF14 4XW, UK; Gareth. Results: Fifteen patients rated nicotine their overall favourite or second favourite, compared with 14 for [email protected]. corticosteroid foam and 11 for 5-ASA and corticosteroid liquids, but this was not significant (p = 0.302). nhs.uk Overall, there was no significant difference in overnight retention. However, the nicotine enema tended to be less well retained in patients with milder urgency but a higher proportion retained it overnight with Submitted 16 December 2004 more severe urgency (p = 0.031 compared with 5-ASA enema). Accepted 8 March 2005 Conclusion: There was no significant difference in patient preference or overall duration of retention for ....................... the four enemas. hile therapeutic enemas are useful in the manage- in the stool—these are often perceived by patients to be the ment of patients with inflammatory bowel disease1–6 most troublesome symptoms. Sigmoidoscopy was not per- Wpoor retention can limit their effect, particularly in formed as the purpose of the score was simply to ensure that patients with active disease associated with urgency of all patients had symptomatically active disease on entry to defecation. Enemas may be retained for only short periods, the study. All gave written informed consent before and in some cases much of the enema may be passed soon participation in the study, which was approved by the after administration. Fear of incontinence while in bed is also South East Wales Local Research Ethics Committee. a problem. Subjects were excluded if they were known to be intolerant During a study of liquid nicotine enemas as treatment for of any of the trial medication, and those who might have ulcerative colitis (UC),7 some patients commented on how been pregnant or were lactating. http://pmj.bmj.com/ readily it was retained—and without discomfort. To examine the hypothesis that nicotine enemas may be better retained, Trial enemas we compared the retention of nicotine enemas with three Three liquid preparations, each about 100 ml in volume, were others, all conventionally used in the treatment of colitis— packaged in identical soft low density polyethylene bottles two of them liquid enemas and one foam enema. The aim of (Forrest Labs, Bexley, UK), together with one foam enema; the study was limited to identification of the patients’ their compositions are below: preference for each enema and duration of retention in on October 2, 2021 by guest. Protected copyright. subjects with active UC—efficacy was not considered. In (1) The prednisolone sodium phosphate liquid enema doing so we used a novel design in which patient preference (Predsol, Celltech) was an aqueous formulation with a was based on exposure to each enema, once only on viscosity of 0.39 mPas, containing 20 mg of prednisolone consecutive nights—a design that breaks with traditional as the sodium phosphate ester in a buffered solution. comparisons in which efficacy is an issue. Included in the formulation are methyl, ethyl, propyl, and butyl 4-hydroxybenzoates as preservatives, disodium METHODS edentate as a chelating agent, sodium acid phosphate Subjects and disodium hydrogen phosphate as buffering agents, A total of 40 consecutive patients, attending the colitis clinic, and sodium hydroxide to adjust its pH to 6.3. who fulfilled diagnostic criteria for UC with active symptoms, (2) The 5-amino salicylate (5-ASA) liquid enema (Pentasa, were reviewed and considered for the study. Twenty four of Ferring Pharma) was an aqueous suspension, pH 4.6 and these patients who required topical treatment were recruited viscosity 0.49 mPas, containing 1 g of mesalazine in to the study. The principal reasons for patients not distilled water. It also contains sodium metabisulphite as participating were unsuitability for topical treatment or an antioxidant. patients declining to take part. The severity of disease on (3) The nicotine liquid enema (SLA Pharma, Watford, UK) entry to the trial was assessed according to a composite was an aqueous formulation that contained 6 mg of scoring system based on the ulcerative colitis disease Activity nicotine base (Seigfried Labs, Zofingen, Switzerland) Index (UCDAI)2 (see box). This composite score was derived from symptoms only; it included stool frequency and Abbreviations: UC, ulcerative colitis; AE, adverse event; UCDAI, consistency, urgency to defecate, and the presence of blood ulcerative colitis disease activity index; 5-ASA, 5-amino salicylate www.postgradmedj.com Enema retention in ulcerative colitis 595 Postgrad Med J: first published as 10.1136/pgmj.2004.031690 on 2 September 2005. Downloaded from Composite score of disease activity Table 1 Demographic details of subjects Sex Stool frequency M/F 13/11 Age, years N 0; usual number of stools for this patient Mean/range 45.1/19–84 N 1; 1–2 stools per day more than usual Extent of colitis Rectal 6 N 2; 3–4 stools per day more than usual Rectosigmoid 7 N 3; at least 5 stools per day more than usual Left sided 6 Total 4 Stool consistency Unknown 1 Previous enema use N 0; formed Yes/no 23/1 N 1; loose Current topical treatment on trial entry None 15 N 2; watery Foam 5 Liquid 3 Urgency of defecation, Suppository 1 N Concomitant oral drugs 0; none 5-ASA 14 N 1; mild Prednisolone 6 N 2; moderate Thiopurines 6 Smoking status N 3; severe (including incontinence) Non/former 11/13 Rectal bleeding N 0; none N 1; streaks of blood with stools less than half the time N 2; obvious blood with stools most of the time power may actually be greater than for 96 different patients N 3; blood alone passed receiving only one treatment as a subject’s responses to different, comparable treatments usually produces positive Maximum total score = 11 correlation when they rank the treatments in order of Adapted from Sutherland et al.2 preference. Subjects were advised to administer enemas slowly and in a consistent way—lying on their side in the left lateral decubitus position, after first warming the enema to body complexed to 400 mg of carbomer powder (Carbopol temperature. They were asked to record their preferences for 974P, Noveon, Cleveland, OH).8 The addition of 100 mg each enema on a diary card and were interviewed either in of xanthan gum (Keltrol, Kelco) made the enema clinic or by telephone after one week. thixotropic and increased its viscosity. Trometamol, TRIS, (S Banner and Son, UK), served as a buffer to Evaluation procedures produce a solution of pH 5.2 with a viscosity of In each case, patients were asked whether the enema was 172 mPas.910 initially retained and then whether it was retained over- night—defined as at least eight hours; if less than the whole (4) The Predfoam enema (Pharmax) was a white mucoad- http://pmj.bmj.com/ night, the duration of enema retention was recorded. They herent aerosol foam, with a dynamic viscosity of also recorded any associated adverse events (AEs). Patients 5.7 mPas and pH of 4.8, which contained prednisolone ranked each of the four enemas, scoring them 1 to 4 for ease metasulphobenzoate sodium, equivalent to 20 mg of of administration, ease of retention both initially and prednisolone per metered dose of about 50 ml. The overnight, degree of any abdominal bloating, and for their product also contained disodium edentate as a chelating overall preference. agent, phenoxyethanol and sorbic acid as preservatives, and propellant gases. Statistical analysis on October 2, 2021 by guest. Protected copyright. Preference scores were compared between enemas using ‘‘Latin square’’ study design and sample size three way analysis of variance modelling by subject, period, Patients who required or were already taking topical and enema. Proportions with initial retention were compared treatment for their colitis were given the four trial enemas between groups by the x2 test. Proportions achieving full in a randomised order, taking one enema on each of four overnight retention were compared by the McNemar test, successive nights. A washout period between enemas was not taking the mid-p two tailed p value and setting significance included as this would have introduced a time delay between at the conventional 5% level. A sub-analysis of the effect of enemas, allowing changes in disease severity to affect the urgency on overnight retention was performed and the results. Twenty four subjects were entered into a Latin square results interpreted cautiously. design in which all permutations of the order of enema administration were included once only; this ensured that RESULTS any carryover effect of earlier enemas affecting subsequent All 24 subjects recruited, 13 male, with a mean age of 45 ones, either by clinical improvement or rectal irritation, did years, completed the study.