1. Constipation: an alternative algorithm? Katherine Clark Conjoint Associate Professor, Newcastle University CMN and HNE LHN

2. Contents Scope of the problem of constipation Current approaches to address the symptom a palliative care population? An alternative approach for palliative care based on a gastroenterology framework?

3. Prevalence of constipation Constipation is a distressing symptom, often complicating the lives of people with specialist supportive and palliative care needs. Prevalence reports vary between studies and stages of illness, ranging from 50% at the time of referral to palliative care services up to 90% of people at the time of admission to an inpatient palliative care unit.

4. Prevalence of constipation Other observational studies document that 60% of people in a palliative care units were charted regular laxatives, despite only 30% of people having constipation listed as a problem on admission*. More than 50% of this same group received more than two laxatives simultaneously. *Clark K, Currow DC, Talley NJ. The use of digital rectal examinations in palliative care in-patients. Journal of Palliative Medicine 2010; 13(7): 797-797

5. Effectiveness of current management? Despite the frequency with which constipation complicates the lives of palliative care patients, the current approach to management is most remarkable for the number of people who fail to achieve adequate symptom control. Reports suggest that 40-70% of palliative care patients treated with laxatives (including peripheral opioid antagonists) continue to experience symptoms.

6. Effectiveness of current management? Recently, the outcomes of 200 patients cared for by specialist palliative care teams were examined. 19% of people treated with laxatives continue to experience fewer than 3 bowel actions per week regardless of which laxatives were prescribed. This group also noted that, in theory, any laxative should be able to normalise bowel function but this is clearly not the case in palliative care patients.

7. Effectiveness of current management? Another case series of 211 palliative care patients was undertaken to explore the relationship between prescribed laxatives and the frequency of documentation of bowel movements. However, bivariate analysis failed to identify any relationship between any laxatives and the frequency of bowel movements *. *Clark K, Lam L, Currow DC. Exploring the relationship between the frequency of documented bowel movements and prescribed laxatives in hospitalised palliative care patients. The American Journal of Hospice and Palliative Medicine

8. Why is this concerning? Laxatives are prescribed with the aim of restoration of regular, soft bowel actions, this does not seem to be reliably the outcome for palliative care patients. This is worrying as the negative impacts of poorly treated constipation may be serious. Aside from pain and discomfort, other associated problems may include nausea, vomiting, anorexia, urinary retention and bowel obstruction.

9. Why is this concerning? Constipation may equal or rival pain as a symptom in terms of the distress and anxiety provoked. In both malignant and non-malignant life-limiting illnesses, constipation has direct deleterious impacts on reported quality of life, with recent data suggesting the greater the number of laxatives prescribed for a person, the more distressed the person’s family is likely to be *. * Clark K, Lam LT, Agar M, Chye R, Currow DC. Retrospective analysis of contributing factors to laxative prescription in hospitalised palliative care patients. Palliative Medicine 2010:24(4):410-8

10. Why is this concerning? Aside from physical and personal costs, poorly palliated constipation has societal costs. Constipated palliative care patients receive more community nursing support and are 20% more likely to be hospitalised. When hospitalised, severely constipated patients receive more nursing time, with a recent study suggesting that earlier and more effective interventions for this group will result in significant clinical and economic benefits.

11. Why is this concerning? Given the predicted rise in the demands for palliative care over the next decade, the need to identify more efficacious approaches to managing constipation for this ever enlarging cohort becomes even more pressing.

12. The currently accepted approaches to palliating constipation in advanced cancer and palliative care populations?

13. Current clinical guidelines Palliative care patients are most likely to identify themselves to be constipated when they experience difficulties with ease of defecation. Palliative care consensus practise guidelines recommend diagnosis and treatment based predominantly on individuals' subjective reports despite the fact that symptoms do not reliably distinguish the site or cause of the problem. Physical examination is used to exclude rectal impaction but little else.

14. Current clinical guidelines Investigations such as biochemistry are used to identify potentially reversible factors; When further investigations are considered necessary, practise guidelines recommend plain abdominal radiographs with little consideration paid to the fact that radiographs are most useful to exclude bowel obstruction only*. *Clark K, Currow DC. Plain radiographs to diagnose constipation in palliative care. Journal of Pain and Symptom Management 2011.

15. Current clinical guidelines Once a bowel obstruction is excluded, patents are commenced on laxatives with EAPC guidelines recommending a combination of softer plus stimulant; The actual guidelines suggest polyethylene glycol and electrolytes or lactulose co-prescribed with a stimulant with the recommended agents including senna or sodium picosulphate. If not successful, the addition of rectal interventions or agents such as methylnaltrexone is suggested.

16. Peripheral opioid antagonists Methylnaltrexone has been studied in palliative care patients to manage the problem of opioid-induced constipation. However, even with well designed and performed trials, problems remain with the routine use of this medication. There is little data to objectively define the magnitude of individual contributing factors, including opioids, to the severity of the symptom experienced. Given the number of contributing factors that may co-exist in one individual at any one time, it is therefore difficult to allocate blame to opioids alone. This observation is supported by the observation that this medication is not universally effective for all people with presumed predominantly opioid-induced constipation.

17. Assessing constipation in non- palliative care? In contrast, the diagnostic approach recommended by gastroenterology guidelines in resistant cases is aimed at defining the underlying pathophysiology. Estimated to affect up to 30% of the general population, gastroenterologists define idiopathic constipation as: –Disturbed neuro-muscular function of the colon, –Disturbed neuro-muscular function of the structures of defecation.

18. Assessing constipation in non- palliative care? Gastroenterologists’ assessments begin at the bedside where specialist guidelines recommend a comprehensive digital rectal (DRE) examination. This is both to exclude rectal faecal impaction and commence the process of screening for: –Pelvic muscle weakness, –Paradoxical anal sphincter contraction or an inability to relax the anal sphincter appropriately.

19. Assessing constipation in non- palliative care? Further investigations recommended by gastroenterology practise guidelines include: –Measurement of the time the contents of the colon to transit through the colon with a colon transit test (CTT), –Assessment of the structures of defecation with: Anorectal manometry, Balloon expulsion tests.

20. Gastroenterology guidelines define four sub-categories of chronic constipation Slow Transit Constipation where passage of colonic contents is prolonged; Pelvic Dyssynergia where paradoxical contraction of the external anal sphincter occurs; Irritable Bowel Syndrome where no dysfunction of the colon or defecation structures is identified but a person constantly perceives or experiences symptoms of constipation; Combination slow transit plus outlet obstruction.

21. A non-palliative care approach to constipation? Despite the subgroup people fall into initial recommendations are conservative : –Correction of under-hydration, –Implementation of a regular gentle exercise program, –Prescribing a dedicated time for toileting optimally in the morning (the diurnal variation of colonic activity), –Exploit the gastro colic reflex, –Ensuring people know how to adopt a semi-squatting position with their knees drawn up towards the chest.

22. Conservative recommendations? Recent observers have reported that combing the conservative recommendations in a severely non-palliative care constipated population significantly improved: –Symptoms as measured by the PAC-SYM, –Quality of life as measured by the PAC-QOL.

23. A non-palliative care approach to constipation? The diagnostic subgroups allow these conservative recommendations to be supplemented with targeted interventions. Specific initial recommendations for people with slow transit problems include the prescription of the oral laxatives with stimulant properties. In comparison, people with disordered defecation may be better managed with general measures plus prescription of regular enemas or suppositories.

24. Gastroenterology vs Palliative Care? Although the mechanisms that result in disturbed bowel actions may be different, the colon and pelvic structures are the same! Acknowledging this allows the problem of constipation in palliative care to be considered in an established framework ie that developed and recommends by gastroenterologists and colorectal surgeons.

25. Subcategorising constipation in advanced cancer and palliative care? The initial step is to define sub-categories applicable to palliative care patients. A logical approach to this is to examine the factors that contribute to altered bowel habits this population. Based on this review, three physical subgroups are proposed: 1.Slow transit of colonic contents; 2.Recto-sigmoid Outlet delay; 3.Overlap Syndrome with diagnostic features of both slow transit and outlet delay.

26. Slow transit of colonic contents This category is based on the numerous factors in palliative care that have been shown to slow colonic contents. Acquired factors know to slow transit commonly occurring in palliative care include: –medications (anti-cholinergics, opioids), –reduced oral intake, –deteriorating performance status presenting as reduced mobility, –metabolic disturbances, –paraneoplastic syndromes. Ideopathic slow transit is likely to occur in 10% of the general community, but how this impacts on the severity of the constipation symptoms experienced during this time in palliative care is not known.

27. Recto-sigmoid Outlet delay Rather than the label of pelvic floor dyssynergias used in functional constipation, the category recto- sigmoid outlet delay is suggested to accommodate problems of the structures of defecation, both functional and acquired. This term is used to include: –The idiopathic constipation symptoms secondary to the functional problems of inappropriate contraction of the external anal sphincter on straining and inadequate relaxation of the internal anal sphincter. –The acquired problems of anal obstruction secondary to myopathic or neuropathic processes.

28. Overlap Syndrome The third group proposed is that of a mixed group of slow transit and outlet delay; This seems intuitively the most likely scenario in palliative care patients given the numerous pathologies likely to be present in one individual, particularly as diseases progress.

29. Is such an approach feasible in palliative care?

30. Diagnosing Slow Transit ? Slow transit of colonic contents is easily and cheaply diagnosed by combining capsules that continue radio- opaque markers with plain abdominal radiographs; This investigation has been piloted in palliative care inpatients and was found to be acceptable to this group. Furthermore, despite regular bowel actions, CTTs were significantly impaired compared to control populations*. * Clark K, Lam L, Chye R, Currow D. Pilot study to document colonic slow transit times in palliative care inpatients. Asia-Pacific Journal of Clinical Oncology 2009;5(Suppl 2)

31. Measuring Colon Transit

32. Diagnosing Outlet Delay? Simple validated approaches exist that allow the integrity of the structures that facilitate defecation to be assessed at the bedside with: –Rectal balloon expulsion, –Hand-held anal manometers.

33. Diagnosing Outlet Delay? Sample Report: Balloon Expulsion Test Normal Result: With the patient seated on a commode, he or she was able to expel a 50-mL rectal balloon within ____ seconds. Abnormal Result: With the patient seated on a commode, he or she was unable to expel a 50-mL rectal balloon in less than 2 minutes.

34. The clinical usefulness of subcategorising constipation in palliative care patients? Undertaking comprehensive assessments would, for the first time, allow clinicians to knowledgably target constipation treatments to the main pathology that have resulted in the symptom of constipation. Such targeted strategies need to be applicable to the palliative care population and to each individual's stage of life.

35. E.g. Slow transit constipation Evidence in non-palliative care supports stimulant laxatives as useful; In palliative care there is reluctance to prescribe stimulants alone for fear of provoking cramping abdominal pain; However, already data exists to suggest that senna alone is likely to be more effective than senna combined with docusate with no increased cramping observed.

36. In summary Constipation remains a troubling symptom in the palliative care population, with the underlying pathology still not well defined. Sub-categorising constipation according to the precedents set in gastroenterology would be the first attempt at allowing structured epidemiological, aetiological, pathophysiological and therapeutic enquiries. As ever, the investigations and interventions must be tailored to the individual's capacity to tolerate them in the context of their stage of life.