Chronic Constipation

Chronic Constipation:
Diagnostic and Treatment Algorithm
Promocon Symposium
March 2015
Anton Emmanuel
National Hospital
for Neurology
& Neurosurgery
Defaecation is complex
Chronic constipation
Got to be full
Have to know that it is full
Got to squeeze it
Got to take the lid off and
put it back on
A categorisation of chronic constipation
Primary1
Secondary2,3
Normal diameter colon
Intrinsic
• Slow transit constipation
• Pelvic floor disorders
• IBS-C
• e.g., colorectal cancer, diverticular
disease
Dilated colon1
• Hirschsprung’s disease
Disease
• Idiopathic megacolon /
megarectum
• Chronic intestinal pseudoobstruction
Today’s focus
Metabolic / endocrine
• e.g., hypercalcaemia, coeliac,
hypothyroidism, hypokalaemia
Neurological
• e.g., spinal cord injury, multiple
sclerosis, Parkinson’s disease
Psychological
• e.g., depression, anorexia nervosa,
bulimia, affective disorders, abuse
Medications
• e.g., opiates, ferrous supplements,
tricyclics, diuretics, antipsychotics
1. Gattuso JM & Kamm MA. Aliment Pharmacol Ther. 1993;7(5):487-500; 2. Blaker P & Wilkinson M. Prescriber 2010;21(9):30–45;
3. Chatoor D & Emmanuel A. Best Prac Res Clin Gastroenterol. 2009;23:517-530.
Chronic constipation:
Symptoms in self-reported constipation
● 1149 participants
● 27.2% self-reported constipation within the past 3 months
● 16.7% and 14.9% constipation according to Rome I and II
Self-reported responders (%)
100
80
60
40
20
0
Straining
BM, bowel movements
Hard/lumpy
stools
Incomplete
emptying
Stool cannot be Abdominal
<3 BM/week
passed
fullness/bloating
Manual
manoeuvres
Pare et al. Am J Gastroenterol 2001;96:3130
Motility
Healthy vs. constipated motor activity1
1. Dinning et al. World J. Gastroenterol 2010;16(41):5162-5172.
Copyright permission pending
5
Measuring transit in clinical practice
Typical radiopaque markers1
Slow transit constipation is characterized by prolonged
delay in the transit of stool through the colon2
20
Number of markers remaining
18
16
14
12
10
8
6
4
2
0
0
Normal Transit Time
Majority of markers
passed by Day 5
1.
2.
Slow transit Time
Markers scattered
throughout colon
Pelvic floor disorder
Most markers in rectum
or rectosigmoid*
6
Chatoor & Emmanuel.
Best Pract Res Clin Gastroenterol. 2009;23(4):517-30; #
Evans et al. Int J Colorect Dis. 1992;7:15-17;
24
48
72
96
120
144
168
Time after ingestion of markers (h)
Normal transit
Mean
±2 standard
deviations
Slow transit
Remaining cubes
Remaining cylinders
Remaining rings
Measuring transit in clinical practice
X-ray of slow transit constipation
Laxatives successfully stopped
Colon diameter
Amount of content emptied
Explain physiology
Slow or normal transit?
7
Rectocoele
8
Intussusception
9
Pelvic Floor Assessment in Clinical Practice
Anorectal physiology
Typical measurements for dyssynergic
defaecation
Obtaining electromyographic recordings1
Musculus sphincter
ani internus
Rectum
Bearing down
Musculus levator ani
Musculus sphincter
ani externus
Electromyograp
hy
(EMG)
1. McCrea et al. World J Gastroenterol. 2008;14:2631-2638.
Copyright permission requested
Anal
sphincter
Abnormal increase in anal pressure
with no relaxation on bearing down
10
Idiopathic Megarectum
These young adults:
- present to casualty repeatedly with impaction
- they are disimpacted by the most junior doctor
- they are then discharged
A single admission to disimpact them
completely
and stabilise them on an
osmotic laxative
will transform their life forever
Suggested treatment algorithm for patients
with chronic constipation
Patient with chronic
constipation
Education; lifestyle
and dietary measures
Initial or subsequent
addition of laxatives
No
Yes
Long-term
management
Adequate relief?
History and physical
examination
No
No
Constipating
drugs?
Alarm features?
Chronic functional
constipation
(Rome III criteria)
Add/switch laxative
Yes
Yes
Technical
examinations as
indicated
Yes
Long-term
management
Adequate relief?
Stop drugs if possible
No
Adequate relief?
Yes
Drug-induced
constipation
Abnormality
identified?
No
No
Yes
Organic disease with constipation,
treat accordingly
No
Stop laxative
and commence
prokinetic drug
(prucalopride in UK)
*assess after 4 weeks
Yes
Adequate relief?
No
Long-term
management
*reassess after 4 weeks
Refractory
constipation
Refer for additional testing following Rome guidelines
for refractory constipation and difficult defaecation
Tack J et al. Neurogastroenterol Motil 2011;23:697-710.
.
Are current laxative options effective for chronic
constipation?
16–40% of those with constipation use laxatives
Symptoms persist despite laxative use
Patients with ongoing constipation symptoms (%)
100
Use laxative
Do not use laxative
80
60
40
20
0
US
UK
FR
GE
Country
Approximately 2000 adults each from: United States, US; United Kingdom, UK;
France, FR; Germany, GE; Italy, IT; Brazil, BR; South Korea, SK
IT
BR
SK
Wald et al. Aliment Pharmacol Ther 2008;28:917
Laxatives for chronic constipation:
Luminal mechanism of action1
GUT WALL
Salts, Sugars and Osmotic agents
Water
binding
in stool
Fibre and Bulking agents
Stool
softening &
lowers surface
tension of stool
Docusate and Stool softeners
Senna and Stimulant agents
Peristalsis
1Tack
& Müller-Lissner. Clin Gastroenterol Hepatol 2009;7:502
Bulking agents
Decreased total gut transit time after 1 month of
psyllium in patients with dyssynergic defaecation1
P<0.05
15
1.
2.
Ashraf et al. Aliment Pharmacol Ther. 1995;9(6):639-47
Cheskin et al. J Am Geriatr Soc. 1995;43(6):666-9
Increased stool frequency after 2 months of
psyllium in patients with normal transit
constipation2
P<0.05
Summary: Tailoring laxatives to the patient, based
on their symptoms and diagnosis
Episodic hard stool
Bulk fibre1
Episodic reduced
frequency
Stimulant1
Slow transit
constipation
Osmotic1
Difficulty evacuating
Glycerine or stimulant
suppository1
Megarectum or
megacolon
Osmotic2
16
1.
2.
Emmauel Ther Adv Gastroenterol 2011;4(1):37-48
Szarka & Pemberton Curr Treat Options Gastroenterol. 2006;9(4):343-50.
3.
4.
If no improvement:
• Increase dose1
• Rational combination e.g.
• Stool softener and
stimulant laxative3,4 or
• bulking agent1
Larkin et al. Palliat Med. 2008;22(7):796-807
Sykes. Cancer Surv. 1994;21:137-46
Prucalopride in chronic constipation
Response over the 12-week treatment period
50
*
% over 12 weeks
40
*
30
*
*
*
*
*
*
* *
*
*
20
10
0
Placebo
*p<0.001 vs. placebo for
both doses of prucalopride
Prucalopride 2 mg
Prucalopride 4 mg
Stanghellini et al. Gut 2009 Abstract [2891]
The 4 mg dose has not been licensed since no incremental benefit was
demonstrated versus the 2 mg dose
Pooled safety and tolerability:
Adverse events
Most common drug-related adverse events
30
Placebo (n=661)
Prucalopride 2 mg (n=659)
Prucalopride 4 mg (n=657)
Patients (%)
25
20
15
10
5
0
Events during treatment period
Events excluding Day 1
Tack et al. Gastroenterology 2008;134:A530
The 4 mg dose has not been licensed since no incremental benefit was
demonstrated versus the 2 mg dose
UCLH data (n=398)
Drug Response
Secondary care
improved
adverse effects
no response
Secondary care
Tertiary care
Tertiary care
Lubiprostone in chronic constipation
 RCT 24mcg Lubiprostone
versus placebo twice daily x4
weeks
 242 patients with chronic
constipation
Results
 “Responders” (>3SBMs/wk) at
4 weeks = 58 v 28%
 NNT= 3.3
Adverse events
Lubiprostone vs placebo
Nausea 32% v 3%
Headache 12% v 6%
Discontinued
8% v 1%
Johanson et al Am J Gastroenterol 2008; 103(1):170-177
FDA statement
“Although the treatment effect is small, lack of a
currently available therapy for this condition
makes it important to have a treatment option
available to patients …..”
Linaclotide
*not licensed in UK/EU
Oral MethylNaltrexone
*not licensed in UK/EU
Limited evidence in nonopioid constipation
Chappell et al. NEJM 2008;359:1071
Diego L et al. Expert Rev Gastroenterol Hepatol 2009 ;3:473-485
Biofeedback
Stool frequency
6
5
4
*
*
*
Number of Sitzmarks
on Day 5
Bowel movements
per week
Evidence
Large amount of short- and long-term data from RCTs for biofeedback
as an effective treatment for chronic constipation1-5
– Greatest effect in patients with pelvic floor dyssynergia:5
*
3
2
1
0
Slow transit (n=12)
20
16
Whole gut transit time
*
12
8
4
0
Pelvic floor disorder (n=34)
*For each follow-up interval, P<0.001
23
1.
2.
3.
Rao. Gastroenterol Clin North Am. 2008;37(3).569-86
Rao et al. Clin Gastroenterol Hepatol. 2007;5(3):331-8
Rao et al. Am J Gastroenterol. 2010;105(4)890-6
4.
5.
Gadel Hak et al. Arab J Gastroenterol. 2011;12(1):15-9
Chiarioni et al. Gastroenterology. 2005;129(1)86-97
*
*
*
Is biofeedback better than stimulant laxatives?
% improvement
biofeedback
bisacodyl
RCT BF vs bisacodyl
(Rao et al AJG 2007)
51 patients, all with dyssinergia
1. Rao et al. Clin Gastroenterol Hepatol. 2007;5:3318
need to strain
Biofeedback – UK version
Emmanuel et al Gut 2001
Transanal irrigation
Evidence
Clinical trial data show success of
transanal irrigation in 65% SCI patients
with constipation1-3
Improved symptoms and quality of
life vs conservative management1,2
Potential adverse effects
Estimated risk of bowel perforation in
patients using transanal irrigation is
≤0.0002% (1 in ~500,000 irrigations)4
1.
2.
Christensen et al. Gastroenterology. 2006;131(3):738-47
Christensen et al. J Spinal Cord Med. 2008;31:560–7
3.
4.
Outcomes of transanal irrigation in patients
(n=79) with chronic idiopathic constipation
after mean follow-up of 21 months3
Idiopathic
constipation*
Success, n
(%)
Slow transit (n=43)
14 (32.6)
Obstructed
defaecation,
but normal transit
(n=30)
13 (43.3)
Undetermined (n=6)
0 (0)
Christensen et al. Dis Colon Rectum. 2009;52(2)286-92
Emmanuel, Spinal Cord 2010:48:664-73
SNS in Constipation
Kamm et al 2010 Gut 59:333-340
Multi-centre study
62 patients
Temporary stimulation
45 (66%) successful
Permanent stimulation
Median follow-up 12 months
Increased bowel motions
Improved toilet symptoms
Improved QOL
Improved cleveland clinic score
Transit improved in 50%
Sacral Nerve Stimulation
38 patients with permanent implants for constipation
Mean follow-up 26 months
Maeda et al, DCR 2010
STARR and the obstructed defaecation syndrome
Methods of assessment
- non-blinded , non-independent proctogram reading
- non-validated newly devised scoring system
Lack of comparative data
Adverse effects in largest study (n=90) with 16 month follow up
18% faecal urgency
13% pain
3% stenosis
NICE IPP 2005
Rectocoele
Can surgery reverse or even arrest pathophysiology?
*
T
*
T
T
*
*
T
T
*
T
T
T
T
Van Laarhoven et al, DCR 1999
**
*
**
TT
Colectomy
Evidence
• Variable treatment ‘success’ rate of
39–100% for total colectomy for slow
transit constipation from a review of 32
studies1
Outcome
Median
Satisfaction or
success
Range
Number
of
studies
86%
39–100%
31
Bowel habit /
day
2.9
1.3–5.0
20
Incontinence
14%
0–52%
16
Diarrhoea
14%
0–46%
16
Recurrent
constipation
9%
0–33%
15
Pain
41%
0–90%
14
Ostomy
5%
0–28%
26
Further surgery
65%
32-100%
22
31
1.
2.
Knowles et al. Ann Surgery 1999;230(5):627–38
Ripetti et al. Surgery 2006;140(3):435-40
3.
Pinedo et al. Surg Endosc. 2009;23(1):62-5
>6 months of reduced bowel frequency, straining excessively,
Algorithm for initial
etc
management of chronic
1. Dilated colon suspected (clinical or abdominal X-ray)
constipation
Organic cause unlikely
2. Organic cause possible (age, red flag symptoms, Coeliac
disease suspected, family history colorectal cancer)
Investigate
Abnormality found
1. Megacolon / Hirschsprung’s disease / chronic intestinal
pseudo-obstruction
2a. Organic luminal disease.
2b. Organic systemic disease (hypercalcaemia,
hypothyroid)
Manage as
appropriate
No
abnormality
Lifestyle advice (liquid intake, rationalise
dietary fibre, simplify any polypharmacy,
toileting advice, address any relevant
psycho-social issues)
Improved
Not
improved
1st line laxative
1. Episodic hard stool: fibre
2. Episodic “missed day”: as required stimulant
3. Regular hard stool and infrequency: osmotic
laxative
4. Difficult emptying: glycerine suppository
Not improved
Improved
2nd line laxative
Combination laxatives (with stool softener or
PEG)
Double dose single agents (indications as
before)
Not improved
Emmanuel et al 2011,
Therap Adv Gastroenterol. 2011 Jan;4(1):37-48
Improved
Specialist input for intractable constipation
Intractable
Constipation
Algorithm for
management of chronic
intractable constipation
1. Consider re-investigating for organic cause
2. Assess for rectal evacuation difficulty (structural and
functional) and assess gut transit
Rectocoele, rectal
prolapse, pelvic floor
incoordination identified
Organic cause
identifed
Manage as
appropriate
If MINOR: pelvic floor
retraining /
biofeedback
If MAJOR and appropriate
symptoms: consider
surgical treatment
Improved
Not improved
Not improved
Consider prokinetic
(5HT-4 agonist) or
probiotic or newer
agent
Improved
Not improved
Consider
increased
suppository or
enema use
Not improved
Emmanuel et al 2011,
Therap Adv Gastroenterol. 2011 Jan;4(1):37-48
No pelvic floor
abnormality
Consider transanal
irrigation or sacral
neuromodulation
Improved
Improved