I ve had it with you and your emotional constipation.

I ve had it with you and your emotional constipation. Washington Irving If Mother had to be told not to put the entire brick of ivory up Junior s hindquarters, constipation is the least of his problems. James Lileks, Highlights from the Golden Age of Bad Parenting Advice

I wish that being famous helped prevent me from being constipated. Marvin Gaye America is a constipated nation If you pass small stools, you have to have large hospitals Dennis Burkitt

Constipation in older people Dov Gandell MDCM November 2 nd, 2013

None Conflicts of Interest

Objectives To review the epidemiology, etiology, and definition of constipation in the older adult To review the literature on the treatment of constipation in older people To identify treatment(s) with evidence for improving constipation outcomes in older adults

Background Which statement is true? A) Equal numbers of men and women suffer constipation B) The prevalence of community dwelling older adults suffering from constipation is not known C) Constipation is defined as fewer than three bowel movements per week D) Age related changes to anatomy and physiology are not thought to account for most cases of chronic constipation

Epidemiology Adult population 14% (95 CI 12% - 17%) Higher prevalence Elderly Community dwelling 20 40% Long term care 50% Lower socioeconomic status Women > Men Mount Sinai Hospital $17 000 yearly in laxative purchases Campbell et al. Factors associated with constipation in a community based sample of people aged 70 years and over. J Epidemiol Community Health 1993;47(1):23 Suares et al. Prevalence of, and Risk Factors for, Chronic Idiopathic Constipation in the Community. Am J Gastroenterol 2011;106:1582

Consequences Functional decline Anorexia Nausea Pain Mortality Stercoral ulceration Perforation Wrenn et al. Fecal Impaction. N Engl J Med 1989;321:658 Ouaissi et al. Lethal Fecaloma. J Am Geriatr Soc 2007;55:965

Etiology Primary Normal transit - 59% Slow transit - 13% Dyssynergic defecation - 25% Secondary Medications, comorbid disease, metabolic, neoplastic Age-related changes Are not believed to account for symptoms of constipation Nyam et al. Long-term results of surgery for chronic constipation. Dis Colon Rectum 1997:40;273 Camilleri et al. Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people. J Am Geriatr Soc 2000:48(9);1142

Definition No universally accepted clinical definition Often treated based on patient complaint Gandell et al. (2012). Evidence-Based Geriatric Medicine, A Practical Clinical Guide. (Holroyd-Leduc, Reddy eds.) BMJ Books. Harari et al. How do older persons define constipation? Implications for therapeutic management. J Gen Intern Med 1997;12:63

Definition: ROME III criteria 2 of 6 symptoms on at least 25% of bowel movements Straining Lumpy or hard stools Sensation of incomplete evacuation Sensation of anorectal obstruction/blockage Manual maneuvers to facilitate defecation Less than 3 defecations per week Loose stools rarely present without laxative use Insufficient criteria for irritable bowel syndrome Longstreth et al. Functional bowel disorders. Gastroenterology 2006;130(5):1480-1491

Background Which statement is true? A) Equal numbers of men and women suffer constipation B) The prevalence of community dwelling older adults suffering from constipation is not known C) Constipation is defined as fewer than three bowel movements per week D) Age related changes to anatomy and physiology are not thought to account for most cases of chronic constipation

Investigations Clinical judgment dictates search for a secondary cause Alarm symptoms Calcium, TSH Digital rectal exam, abdominal plain film Evidence base lacking to guide pursuit of a primary cause $2752 per adult patient Infrequently done prior to a therapeutic trial Rantis et al. Chronic constipation-is the work up worth the cost? Dis Colon Rectum 1997;40:280

Treatment options Systematic review, 2012 Age > 65, randomized trial design 16 trials identified Bulk agents (fibres) 7 trials Osmotic agents 4 trials Stimulants 2 trials Stool softeners 1 trial Prokinetics 1 trial Biofeedback 1 trial Gandell et al. Treatment of constipation in older people. CMAJ 2013;185(8):663

Results N = 1067 elder participants Mean age 75.9 Setting 323 long term care 280 outpatient setting 91 acute care 80 rehabilitation unit Mean study duration 4 ¾ weeks Gandell et al. Treatment of constipation in older people. CMAJ 2013;185(8):663

Results: Bulk Agents Which of the following is true? A) bulk agents can cause allergic reactions B) mechanical GI obstruction has been reported with bulk agents C) beneficial outcomes have not been consistently demonstrated in trials of bulk agents D) bulk agents exert their effect by increasing stool mass and/or volume

Bulk Agents Mechanism of action Soluble, non-absorbable dietary fibres hold water in stool Adverse effects Bloating and flatulence Rare allergic reactions and mechanical obstruction Dose Gradually increase to 20 to 30 grams (dietary and supplemental) daily Cost 25 cents per 3 gram dose (Metamucil)

Results: Bulk Agents Fibre Psyllium 2 trials Cheskin N = 10 24g daily v. placebo over 4 weeks Stool frequency (SF) 1.3/d v. 0.8/d, p<0.1 Quality score (QS) 2/5 Ewerth N = 10 12g daily v. placebo over 8 weeks SF 0.98/d v. 1.02/d, NS QS 3/5 Sources of bias: blinding, small sample sizes Cheskin et al. J Am Geriatr Soc 1995;43:666 Ewerth et al. Acta Chir Scand Suppl 1980;500:49

Results: Bulk Agents Fibre Bran 2 trials Rajala N = 51 Wheat bran in yoghurt twice daily for 2 weeks SF bran 5.9 ± 3.8 per week v. 4.3 ± 1.8, p<0.05 QS 2/5 Sources of bias: blinding, mixture of laxatives Snustad N = 80 10g daily of fibre in cookies SF difference NS QS 2/5 Sources of bias: unknown loss to follow-up Rajala et al. Compr Gerontol [A] 1988;2:83 Snustad et al. J Nutr Elder 1991;10(2):49

Results: Bulk Agents Fibre Galactooligosaccharides (GOS) - 3 trials Sairanen N = 43 SF 8.0 ± 0.6/wk GOS v. 7.1 ± 0.5/wk placebo, p=0.011 Surakka N = 42 SF Δ in BM/5 days 0.5 GOS v. -0.2 placebo, p=0.084 Teuri N = 18 SF 7.1/wk GOS (95 CI 3 15) v. 5.9/wk (95 CI 1 to 14) Sairanen et al. Eur J Clin Nutr 2007;61:1423 Surakka et al. Int J Probiotics Prebiotics 2009;4:65 Teuri et al. Ann Nutr Metab 1998;42:319

Results: Bulk Agents Which of the following is true? BOTTOM LINE A) bulk agents can cause allergic reactions 1 low quality trial with positive results B) mechanical obstruction has been reported A with reasonable bulk agents choice in ambulatory elders with mild constipation C) beneficial outcomes have not been consistently shown in trials of bulk agents Aim for 20 to 30 grams daily from dietary and supplemental sources D) bulk agents exert their effect by increasing stool mass and/or volume

Results: Osmotic Agents Identify the incorrect statement: A) Lactulose is the most effective osmotic laxative B) Magnesium toxicity from magnesium-based laxatives should be considered in some patients C) Polyethylene glycol is available over the counter D) Osmotic laxatives exert their effect by equilibrating colonic and plasma tonicity

Osmotic Agents Mechanism of action Promote secretion of water into the colonic lumen to maintain isotonicity with plasma Adverse Effects Bloating, flatulence, diarrhea Dose Polytethylene glycol (PEG) 17 34 grams/day Lactulose 15 30 ml daily to twice daily Cost PEG $1 to $2/dose Lactulose $2/dose

Results: Osmotic Agents Polyethylene Glycol (PEG) 1 trial Zangaglia N = 57, 7.3g twice daily v. placebo for 8 weeks SF per week 6.6 ± 2.7 PEG v. 3.7 ± 1.9, p<0.002 QS 4/5 Rome criteria as inclusion Randomization not described Zangaglia et al. Mov Disord 2007;22:1239

Results: Osmotic Agents Lactulose/Lactitol 3 trials Sanders N = 55, 20g lactulose daily for 12 weeks SF 0.63±0.31/d lactulose v. 0.58±0.3/d, p<0.02 QS 3/5 Sources of bias: randomization, blinding not described Wasselius-De Casparis N = 103, 15ml lactulose daily 50% syrup Success (no use of additional laxatives) 86% lactulose v. 60%, p<0.02 QS 2/5 Sources of bias: follow-up not reported Sanders et al. J Am Geriatr Soc 1978;26:236 Wasselius-De Casparis et al. Gut 1968;9:84

Results: Osmotic Agents Lactulose/Lactitol 3 trials Vanderdonckt N = 46, 20g lactitol daily for 4 weeks SF 6 to 7/wk (range) lactitol v. 3 to 4, p<0.001 QS 3/5 Sources of bias: randomization, blinding not described, absence of point estimate Vanderdonckt et al. J Clinical and Exp Gerontol 1990;21:171

Results: Osmotic Agents Identify the incorrect statement: BOTTOM A) Lactulose LINE is the most effective osmotic laxative 1 high quality study with a positive result for PEG B) Magnesium toxicity from magnesium-based laxatives should be considered in some patients 3 low to mid quality studies with positive results for Lactulose C) Polyethylene glycol is available over the counter Use of PEG and lactulose in older adults is supported by D) the Osmotic literature laxatives exert their effect by equilibrating colonic and plasma tonicity

Results: Stool softeners Regarding stool softeners, choose the correct answer A) They have been shown to improve stool softness according to the Bristol Stool Chart B) Docusate calcium is more effective than docusate sodium and is more convenient with once daily dosing C) The red translucent nature of the capsule helps promote adherence D) They do not have level 1 evidence to support their use

Stool softeners Mechanism of action Anionic surfactants easing the interaction of water with solid stool Adverse effects Generally well tolerated Dose Dioctyl sodium sulfosuccinate 100 mg twice daily Docusate calcium 240 mg once or twice daily Cost $0.30 to $0.50 cents per dose

Results: Stool softeners Dioctyl Sodium Sulfosuccinate (DSS) 1 trial Hyland N = 40 100mg 3 times daily for 4 weeks SF mean difference 1.0±0.29 more stools per week DSS than placebo, p<0.01 Q/S 3/5 Sources of bias: non-constipated participants given placebo excluded from analysis, randomization and blinding not described Hyland et al. Practitioner 1968;200:698

Results: Stool softeners Regarding stool softeners, choose correct answer BOTTOM LINE A) They have been shown to improve stool softness The according efficacy to of the stool Bristol softeners Stool is unknown Chart B) Docusate calcium is more potent than docusate sodium and is therefore dosed once instead of twice daily C) The red translucent nature of the capsule helps promote adherence D) They do not have level 1 evidence to support their use

Results: Stimulants Stimulants, choose the correct answer A) Melanosis coli is a potential adverse effect that should be screened for with prolonged use B) The maximum recommended daily dose of Senokot is 8 tablets per day C) Stimulants have evidence to support their use in younger adults but not in older adults D) Trials support the use of stimulants when constipation is primarily the result of opioid analgesia

Stimulants Mechanism of action Increasing intestinal motility and secretions Adverse effects Abdominal cramps, hypokalemia, pseudomelanosis coli Dose Sennoside up to 68.8 g/d in divided doses Bisacodyl 5 10 mg/d orally or rectally Cost Sennokot $0.15 to $0.20 per tablet

Results: Stimulants Sennosides/chinese herbal formulation 2 trials Bub N = 92 20g sennosides for 4 weeks 4.14 more BM over 4 weeks with stimulant than placebo, p=0.017 QS 4/5 Sources of bias: baseline laxatives permitted to continue Huang N = 90 1.5g to 4.5g CCH1 SF per week 5.6±2.0 CCH1 v. 4.6±2.5, p=0.049 QS 3/5 Sources of bias: formulation contained magnesium oxide, randomization and blinding method not reported Bub et al. J Am Med Dir Assoc 2006;7:556-61 Huang et al. J Altern Complement Med 2001;17:639-46

Results: Stimulants Stimulants, choose the correct answer BOTTOM LINE A) Melanosis coli is a potential adverse effect that should be screened for with prolonged use The efficacy of stimulant laxatives is unknown B) The maximum recommended daily dose of Senokot is 8 tablets per day C) Stimulants have robust evidence to support their use in younger adults but not in older adults D) Trials support the use of stimulants when constipation is primarily the result of opioid analgesia

Results: Prokinetics Regarding prokinetics, choose the correct answer A) Cisapride and tegaserod are not related to the current generation prokinetic, prucalopride B) Prucalopride (Resotran) has been approved for use in Canada C) There are multiple trials revealing benefit of prucalopride in older individuals D) Cardiac toxicity should not be a concern

Prokinetics Mechanism of action Stimulates the 5-hydroxytryptamine-4 (5-HT 4 ) receptors in the intestine which induces peristalsis Adverse Effects Abdominal pain, diarrhea, nausea, vomiting, flatulence, headache Dose 1 mg daily over 65, 2 mg daily adults Cost $2 - $3 per pill

Results: Prokinetics Prucalopride 1 trial N = 300 1,2, or 4 mg once daily for 4 weeks SF week 1 48.7% 3 BM per week v. 26.1%, p<0.05. 4 mg dose QS 5/5 Sources of bias: multiple statistical tests, only 1 time point reaching significance for primary outcome Muller-Lissner et al. Neurogastroenterol Motil 2010;22:991-8

Results: Prokinetics Regarding prokinetics, choose the correct answer BOTTOM LINE A) Cisapride and tegaserod are not related to the current generation prokinetic, prucalopride The efficacy of prucalopride in older adults is unknown B) Prucalopride (Resotran) has been approved for Adverse events rates from post marketing surveillance will use in Canada be informative C) There are multiple trials revealing benefit of prucalopride in older individuals D) Cardiac toxicity should not be a concern

Other noteworthy information Evidence from Younger adults Enemas Fluid intake Exercise

American College of Gastroenterology Guidelines Polyethylene glycol Grade A recommendation Increasing stool frequency and consistency Lactulose Grade A recommendation Increasing stool frequency and consistency Psyllium Grade B recommendation Increasing stool frequency Insufficient evidence Other fibres, magnesium, stimulants Brandt et al. Am J Gastroenterol 2005; 100(Suppl. 1):S5 - S21

Polyethylene Glycol v. Lactulose Systematic review 10 RCTs comparing PEG and lactulose Adults only recruited in 4/10 studies N = 868 participants 5 trials reported stool frequency per week Taken singularly, all showed that PEG resulted in higher stool frequency per week when compared with lactulose. Elderly subgroup not analyzed Lee-Robichaud et al. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.:CD007570

Enemas Long term care RCT Long term care patients, N = 206, mean age 85 30 g lactulose daily v. 30 g lactulose daily AND glycerine suppository daily tap water enema weekly Primary endpoint at 2 months Mean number of fecal incontinence episodes per patient Lactulose 24±11.5 v. Lactulose and PR 24±10.8, p=0.9 Chassagne et al. Age & Ageing 29(2):159-164

Fluid Intake Random selection of elderly, New Mexico Medicare patients Home interview, questionnaire, examination Fluid intake, falls, constipation, fatigue, orthostatic BP N = 883, mean age 74.1 71% felt intake > 6 glasses per day Fluid intake not associated with lying and standing BP Falling frequency of chronic constipation fatigue Lindeman J Gerontol A Biol Sci 2000;55:M361-65

Fluid Intake Risk factors for constipation in LTC residents 3 month cohort study of nursing home residents who did not have constipation at baseline 7% developed constipation Poor consumption of fluids OR 1.49 (95 CI 1.21 1.82), p<0.001 Not further defined, data from the Minimum Data Set (MDS) Robson et al. Dis Colon Rectum 2000;43:940-43

Exercise Long term care RCT N = 157, mean age 81.7, 6 months Resistance training (twice/week) Functional-skills training (twice/week) Combination of above (once each, total twice/week) Education as control group (group discussions) Proportion of constipated subjects at 6 months, NS Resistance 22%, Functional 23%, Combo 29%, Control 9% 20% constipated at baseline Chin A Paw et al. BMC Geriatrics 2006;6:1-9

In older adults, the evidence reveals polyethylene glycol and lactulose produce more frequent and softer bowel movements than placebo