Ive 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 2nd, 2013

Conflicts of Interest

• None

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)


• 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


• 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


• 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


• Which of the following is true?

– A) bulk agents can cause allergic reactions

– B) mechanical obstruction has been reported with bulk agents

– C) beneficial outcomes have not been consistently shown in trials of bulk agents

– D) bulk agents exert their effect by increasing stool mass and/or volume

BOTTOM LINE •1 low quality trial with positive results • A reasonable choice in ambulatory elders with mild constipation •Aim for 20 to 30 grams daily from dietary and supplemental sources

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


• 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


• 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


• 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


• 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

BOTTOM LINE •1 high quality study with a positive result for PEG • 3 low to mid quality studies with positive results for Lactulose • Use of PEG and lactulose in older adults is supported by the literature

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


• 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


• Regarding stool softeners, choose correct answer

– A) They have been shown to improve stool softness according to the Bristol Stool 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

BOTTOM LINE •The efficacy of stool softeners is unknown

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 – 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 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

BOTTOM LINE • The efficacy of stimulant laxatives is unknown

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-HT4)

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


• 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


• 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

BOTTOM LINE •The efficacy of prucalopride in older adults is unknown •Adverse events rates from post marketing surveillance will be informative

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

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Ive had it with you and your emotional constipation