Management of constipation – the evidence The Royal Society of Medicine Palliative Care Conference Scarborough 2006 Dr Iain Lawrie Specialist Registrar in Palliative Medicine The Yorkshire Deanery

Constipation through the ages What is constipation? The problem - the general population - in palliative care Management options & evidence

Historical perspectives Use of purgatives, enemas & emetics since ancient times Bile (one of the “humors”) Prophylactic as well as treatment 17th century “enema craze” Modern, Western diet Continuing misconceptions

What is constipation? Many definitions, no consensus. e.g. Dissatisfaction with frequency of bowel movements Hard stool consistency Discomfort on defecation / straining Sensation of incomplete evacuation Less than 3 bowel movements per week Less than 35g of stool per day Stool water weight less than 70% GITT longer than 5 days

The general population Prevalence of 10% 1/3 of the populations of Western industrialised suffers occasionally More common in women and with ageing

Palliative care patients Common Distress levels rival that of pain 50% of hospice admissions report constipation (likely an underestimate) 85% of patients taking opioids require laxatives

Management strategies Basic measures exercise, fibre, fluids Laxatives Bulk-forming Osmotic Stimulant Softeners others

Bulk-forming laxatives Cannot be broken down (minimal absorption) Mostly natural or synthetic polysaccharides Absorb water in the intestine Not recommended in palliative care Examples: ispaghula husk, methylcellulose, sterculia, bran

Level II evidence, Grade B Ispaghula husk n Freq. Consist. Transit Time Subj. Cheskin et al. (1995) 10    nc Ashraf et al. (1995) 22    nc Fenn et al. (1986) 201   nc  Dettmar & Sykes (1998) 381 nc  nc  McRorie et al. (1998) 170   nc nc Level II evidence, Grade B

Level III evidence, Grade C Methylcellulose Celevac® No placebo-controlled trials Level III evidence, Grade C

Level III evidence, Grade C Bran Several studies seem to suggest benefits Added bran …improved stool frequency & consistency (Anderson & Whichelow 1985) [But] compared to a normal diet, fewer laxatives required, improved frequency & consistency, but more assistance with defecation required (Mantle 1992) Level III evidence, Grade C

Osmotic laxatives Act by increasing the amount of water in the large bowel Not (or little) absorbed during intestinal transit Water in food remains bound & in bowel lumen Include magnesium salts, saccharines, & macrogols

Level III evidence, Grade C Magnesium salts Magnesium hydroxide (milk of magnesia) Compared to a bulk laxative – Mg caused more frequent bowel movements, more normal stool consistency & fewer additional laxatives required Risk of raised serum Mg levels Level III evidence, Grade C

Level II evidence, Grade B Saccharines n Freq. Consist. Comments Bass & Dennis (1981) 24 +  flatulence Wesselius-De Casparis et al. (1968) 103 (success rate 80% [vs 33%] in constipated patients) Sanders (1978) 47  fewer enemas reduced flatulence Level II evidence, Grade B

Level I evidence, Grade A Macrogols n Freq. Consist. Comments Andorsky & Goldner (1990) 32   Minor loose stool & cramp Attar et al. (1999) 99  Better tol. than lactulose Cleveland at al. (2001) 23  Improved symptom scores Corazziari et al. (1996) 48    straining,  laxatives Corazziari et al. (2000) 70   77%/20% not constipated DiPalma et al. (2000) 151    ease of defecation Freedman et al. (1997) 57 PEG>lactulose>placebo Chaussade & Minic (2003) 263    straining Level I evidence, Grade A

Level III evidence, Grade C Stimulants Senna, sodium picosulfate, bisocodyl, No placebo-controlled trials of any quality Conflicting evidence of combinations vs stimulants alone Codanthramer similar to senna + lactulose, strong preparation may be better Level III evidence, Grade C

Level III evidence, Grade C Stool softeners Docusate sodium, liquid paraffin Effect is modest at best Level III evidence, Grade C

Others Cisapride – no longer marketed Colchicine – 3 small studies, unclear efficacy Misoprostol – 1 small study, unclear efficacy Erythromycin – 1 small pilot study, possible benefit Naloxone – some evidence, further studies underway

In summary… Fibre – not recommended in palliative care Stimulants – beneficial Softeners – possibly beneficial Osmotics Lactulose – overrated & causes side effects Macrogols – laxative of choice in OIC Prevention is better than cure!

References Ashraf W et al. Aliment Pharmacol Ther 1995; 9: 639-47 Andorsky RI, Goldner F. Am J Gastroenterol 1990; 85: 261-5 Ashraf W et al. Aliment Pharmacol Ther 1995; 9: 639-47 Attar A et al. Gut 1999; 44: 226-30 Bass P, Dennis S. J Clin Gastroenterol 1981; 3: 23-8 Chaussade S, Minic N. Aliment Pharmacol Ther 2003; 17: 165-72 Cheskin LJ et al. J Am Geriatr Soc 1995; 43: 666-9 Cleveland MV at al. South Med Assoc J 2001; 94: 478-81 Corazziari E et al. Dig Dis Sci 1996; 41: 1636-42 Corazziari E et al. Gut 2000; 46: 522-6

Dettmar PW & Sykes J. Curr Med Res Opin 1998; 14: 227-33 DiPalma JA et al. Am J Gastroenterol 2000; 95: 446-50 Fenn GC et al. Br J Clin Pract 1986; 40: 192-7 Freedman MD et al. J Clin Pharmacol 1997; 37: 904-7 McRorie JW et al. Aliment Pharmacol Ther 1998; 12: 491-917 Anderson AS, Whichelow MJ. Hum Nutr Appl Nutr 1985; 39: 202-7 Mantle J. Cancer Nursing 1992; 88:15-18 Sanders JF. J Am Geriatr Soc 1978; 26: 236-9 Wesselius-De Casparis A et al. Gut 1968; 9:84-6