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Contemporary Management of Functional Dyspepsia

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GERD Dyspepsia. Pathophysiology of Functional Dyspepsia ... GERD Dyspepsia Dyspepsia Structural Disease. Relief of pain. with food. Early satiety ... – PowerPoint PPT presentation

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Title: Contemporary Management of Functional Dyspepsia


1
Contemporary Management of Functional Dyspepsia
  • This educational program, approved by the
    Canadian Association of Gastroenterology, is
    sponsored by an unrestricted educational grant
    from

2
Learning Objectives
  • Review the definition and presentations of
    dyspepsia
  • Understand dyspepsia and its differential
    diagnosis
  • Rationalize testing for dyspepsia
  • Choose an optimal therapeutic approach for
    dyspepsia

3
Definitions and Epidemiology of Dyspepsia
4
Dyspepsia - Definition
  • A group of symptoms which alert clinicians to
    consider disease of the upper gastrointestinal
    tract

(British Society of Gastroenterology, 1996)
5
Epidemiology of Dyspepsia
DIGEST, 1996 The Domestic/International
Gastrointestinal Disease Study. Canadian
Highlights
  • Randomly selected 1036 adults across Canada
  • Examined
  • 1. Severity of dyspepsia symptoms 2. Quality of
    life

6
Overall Prevalence of Dyspepsia in Canada
30
30
29
27
25
British Columbia
Prairie Provinces
Ontario
Quebec
Atlantic Provinces
(DIGEST, 1996)
7
Dyspepsia in Canada Sample Breakdown
Total Sample
No dyspepsia 71
Dyspepsia 29
Acute dyspepsia 6.5
Chronic dyspepsia 22.5
Less than 1 Month
(DIGEST, 1996)
8
Social Impact of Dyspepsia
70
60
50
40
30
20
10
0
Not At All
Slightly
Moderately
Quite A Lot
Extremely
Extent to which dyspepsia has interfered with
normal social activities
(DIGEST, 1996)
9
Quality-of-Life
Subjects with no dyspepsia Subjects with
chronic dyspepsia
Score (Psychological General Well Being Index)
Anxiety Positive Depressed Self General Vitality
Well Being Mood Control Health
Domain
(DIGEST, 1996)
10
Functional Dyspepsia - Definition
  • Chronic or recurrent upper GI symptoms not
    explained by biochemical or structural
    abnormalities (does not imply that there is no
    physiological basis)
  • Appropriate evaluation using standard diagnostic
    tests reveals no abnormalities
  • Also known as nonulcer dyspepsia, essential
    dyspepsia, idiopathic dyspepsia

(Talley N. Scand J Gastro 19911827)
11
Dyspepsia
Functional Dyspepsia
Non-GI Causes of Symptoms (cardiac
disease, muscular pain, etc.)
Structural Dyspepsia (GERD, PUD,
pancreatic disease, gallstones, etc.)
12
Symptoms of Functional Dyspepsia
Ulcer-like Dominant Dysmotility-like Dominant
13
Major Causes of Dyspepsia
Williams 1988 Stanghellini 1996 Heikkinen 1996
(n1386) (n1057) (n766)
of Patients with Diagnosis
Gastric Cancer Peptic Ulcer Esophagitis/ Functiona
l
GERD Dyspepsia
14
Pathophysiology of Functional Dyspepsia
15
What are the possible causes of functional
dyspepsia?
  • Altered enteric visceral perception
    (hyperalgesia)
  • Altered enteric motor function
  • Altered CNS function
  • Helicobacter pylori

16
Pathogenesis Pathophysiology of Dyspepsia
  • Behavioural factors
  • Gastritis
  • H. pylori infection
  • Increased visceral perception
  • Altered motility

17
Mechanisms Underlying Increased Sensory Perception
Reduced descending inhibition
  • Increased sensory input

18
Mechanisms Underlying Altered Motility in
Dyspepsia
  • Stress
  • Behavioural Factors

Local Factors Gastritis H. pylori infection
Abnormal Motility
  • Decreased antral motility
  • Impaired fundal relaxation

19
Putative Pathogenesis of Dyspepsia
Stress
ANS Imbalance
Increased Sensitivity
Increased Afferent Activity
Low Grade Inflammation HP Infection
Impaired Motor Activity Accommodation
Altered Motor Sensory Function
DYSPEPSIA
20
Altered Enteric Visceral Perception (Hyperalgesia)
in Functional Dyspepsia
21
Proposed Mechanisms of Hyperalgesia
Role of Inflammation
Mucosa Lamina propria Neuromuscular layer
Irritation or Infection
Acute Inflammation
Immune Activation
Altered Neuromuscular Function
Resolution
Normal
Persistent Altered Neuromuscular Function
In some (Genetic)
22
Proposed Mechanisms of Hyperalgesia
Is there evidence of inflammation in functional
dyspepsia?
  • Endoscopic evidence of gastritis in some patients
  • Increased mast cells in the lamina propria in
    some patients
  • Some patients have infection with Helicobacter
    pylori

Hypothesis Low-grade inflammation can cause
altered motor function, and altered sensitivity
23
Proposed Mechanisms of Hyperalgesia
Normal Pathways
Pain Perception
Cortex
Descending inhibitory fibres
Spinal Cord - ANS. Input 2nd order
neurons Dorsal horn nucleus Dorsal root
ganglion Sensory nerve endings in gut
24
Proposed Mechanisms of Hyperalgesia
Peripheral Hyperalgesia
Amplification
Hyperplasia of D.H.N.
Amplification
Hyperplasia of D.R.G.
Irritation or Low Grade Inflammation
Recruitment of silent sensory fibres -
Amplification
25
Proposed Mechanisms of Hyperalgesia
Central Hyperalgesia
Pain
Loss of Descending Inhibition
Peripheral Signals
26
Proposed Mechanisms of Hyperalgesia
Drug Effects on the CNS-Enteric Nervous System
Pain Perception
Cortex
Pharmacological Options ? opiates,
tricyclics 5HT3 antagonists
Spinal Cord Descending inhibitory fibres -
ANS. Input 2nd order neurons Dorsal horn
nucleus Dorsal root ganglion Sensory nerve
endings in gut
Clonidine ? opiates 5HT3 antagonists
Substance P CGRP antagonists
NSAIDs ? opiates 5HT3 antagonists
27
Visceral Hyperalgesia in Functional Dyspepsia
  • Patients with functional dyspepsia have normal
    somatic pain perception
  • Visceral sensation is diffusely altered in
    functional dyspepsia, based on balloon distension
    studies in stomach, esophagus, and rectum

(Trimble K. Dig Dis Sci 1995401607)
28
Visceral Hyperalgesia in Functional Dyspepsia
Controls (n10) Patients with functional
dyspepsia (n10)
p lt 0.005
p 0.001
Volume of Gastric Distension (mLs)
(Bradette M. Dig Dis Sci 19913652)
29
Altered Enteric Motor Function in Functional
Dyspepsia
30
Upper GI Motility in Functional Dyspepsia
  • Impaired reflex fundal relaxation
  • Impaired gastric compliance/receptive relaxation
    to food ingestion
  • Weak postprandial antral contractions
  • Delayed gastric emptying
  • Small bowel motor dysfunction

31
Upper GI Motility in Functional Dyspepsia
Abnormal Fundic Relaxation in Response to Meal
in Functional Dyspepsia
Normal
Fundic accommodation or receptive relaxation
Meal
Impaired fundic accommodation with a
redistribution of food to antrum
Functional dyspepsia
(Gilja O. Dig Dis Sci 199641689)
32
Impaired Accommodation in Functional Dyspepsia
P lt 0.05
Differences in area measurements in a sagittal
section of proximal stomach, between patients
with functional dyspepsia and healthy controls.
SEM bars are shown.
(Gilja O. Dig Dis Sci 199641689)
33
Weak Postprandial Antral Contractions in
Functional Dyspepsia
Normal
Functional Dyspepsia
  • Postprandial antral hypomotility is common
  • Can also be seen in PUD or gastritis

(Camilleri M. Dig Dis Sci 1986311169. Kerlin
P. Gut 19893054)
34
Delayed Gastric Emptying in Functional Dyspepsia
  • Studies have found delayed gastric emptying for
    solids, in 30 to 82 of patients with functional
    dyspepsia

35
Small Bowel Motor Dysfunction in Functional
Dyspepsia
  • In patients with more severe symptoms
  • Hyperactive or uncoordinated duodenal
    contractions
  • Absent or abnormal migrating myoelectrical
    complexes

(Kerlin P. Gut 19893054)
36
Altered CNS Function in Functional Dyspepsia
37
CNS Factors
Psychological factors to be considered in the
pathogenesis of functional dyspepsia
  • Anxiety
  • Depression
  • Sexual abuse
  • Sleep deprivation
  • Stressful events

The role of psychological factors in functional
dyspepsia is not as clearly established as it is
in IBS
38
Functional Dyspepsia and Irritable Bowel Syndrome
44
29
of Patients with Functional Dyspepsia who also
have IBS
Ulcer-like Dysmotility-like Dyspepsia Dyspepsia
(Jones R. Gut 199031401)
39
Helicobacter pylori in Functional Dyspepsia
40
Is H. pylori a Factor in Functional Dyspepsia?
  • Controversial
  • Some evidence - biological plausibility -
    prevalence (45 to 70 in dyspeptics, 13 to
    60 in controls) - eradication studies

41
H. pylori Eradication Studies in Functional
Dyspepsia
No Benefit from Length of Benefit from Length
of H. pylori Follow-up H. pylori Follow-up Eradi
cation (yr) Eradication (yr)
  • Veldhuyzen van Zanten, 1995 0.5 Lazzaroni,
    1996 0.5
  • Elta, 1996 3 Trespi, 1994 0.5
  • Schutze, 1996 1 McCarthy, 1995 1
  • Sheu, 1996 1

42
Canadian Economic Analysis H. pylori Eradication
in Undiagnosed Dyspepsia
  • Based on an American analysis
  • Examined management of Hp-seropositive patients
  • Scope first strategy 401 Treat Hp first 345

(Adapted from Offman J. Ann Int Med 1997126280)
43
Testing for H. pylori
Test Sensitivity Specificity Cost Comments
  • C13 or C14 90 to 100 96 to 100 Limited -
    requires urease breath hospital
    nuclear test medicine department
  • Serology 91 to 98 75 to 80 Widely
    available through commercial labs and
    Public Health
  • Capillary 85 to 90 75 to
    80 Office test, must be blood
    serology purchased by doctor administered
  • Endoscopic 99 99 Requires
    specialist biopsy Invasive

(Cutler A. Gastro 1995109136. Megraud F. Scand
J Gastro 199621557)
44
H. pylori Eradication Regimens (All given for one
week)
  • Treatments of Choice

Regimen PPI Antibiotics
PPI - AC BID Amoxicillin 1 g bid Clarithromycin
500 mg bid PPI - MC BID Metronidazole 500 mg bid
Clarithromycin 250 mg bid
Alternate
PPI - BMT BID Bismuth 2 tabs qid Metronidazole
250 mg qid Tetracycline 500 mg qid
45
Management of Dyspepsia
46
Suggested Approach for Management of Dyspepsia
Dyspepsia
Initial interview and examination
Functional dyspepsia
Structural disease or alarm symptoms
Dysmotility-like symptoms dominant
Ulcer-like symptoms dominant
Education/lifestyle modification
Education/lifestyle modification
Test Hp

-
Eradicate
Trial of acid suppression
Trial of prokinetic medication
Success
Fail
Fail
Fail
Success
Success
Investigate/refer
47
Interview and Examination Objectives
  • Initiate a symptom-based diagnosis
  • Address patients concerns and expectations
  • Explore psychosocial issues, patterns of illness
    behaviour
  • Educate

48
Interview and Examination - Symptoms and Signs
Suggest Suggest Ulcer-like Suggest
Dysmotility-like Suggest GERD
Dyspepsia Dyspepsia Structural Disease
  • Heartburn Burning pain Nausea Weight loss
  • Regurgitation Bloating Dysphagia
  • Reflux

Relief of pain with food
Vomiting Bleeding Palpable mass
Early satiety Pain worse with food
Localized epigastric pain Nocturnal/ fasting pain
49
Suspected Functional Dyspepsia - Who to
Investigate?
  • Over 50 years of age, with new onset of symptoms
  • Failed therapy
  • Cancer fear
  • Symptoms that are severe as perceived by patient
    or physician

50
Choice of Investigation for Ulcer-like Dyspepsia
Endoscopy UGI Series
  • More expensive Less expensive
  • Issues of access/waiting Easy access, usually
    short lists can be a problem waiting time
  • Allows for biopsy If cancer is found,
    endoscopy (cancer, Hp) will be needed
  • Allows diagnosis of Often misses mucosal
    lesions mucosal lesions (erosions)
  • Preferred investigation for Alternative,
    especially if dyspepsia access is a concern

51
Investigation of Dysmotility-like Dyspepsia
  • Investigations are frequently normal
  • Reserved for patients with severe symptoms,
    vomiting dominant, unresponsive to therapy
  • Solid-phase gastric emptying test may be useful

52
Management of Functional Dyspepsia
53
Management of Functional Dyspepsia
Functional Dyspepsia
General treatment and specific management based
on dominant symptom complex
Ulcer-like
Dysmotility-like
Follow-up within 3 to 6 weeks
54
Management of Ulcer-like Functional Dyspepsia
Ulcer-like Symptoms Dominant
Education/lifestyle modification
Test Hp

-
Eradicate Hp
Trial of acid suppression
Reassess
Success
Failure
Investigate
Trial of prokinetic
55
Lifestyle Modification for Patients with
Functional Dyspepsia
  • Small frequent meals
  • Stop smoking
  • Reduce alcohol
  • Reduce caffeine
  • Avoid irritating foodstuffs
  • Maintain an ideal weight
  • Review medications

56
Acid Suppression Therapy for Ulcer-like
Functional Dyspepsia
  • H2-receptor antagonist for 4 weeks
  • OR
  • Proton pump inhibitor for 2 weeks

57
Management of Dysmotility-like Functional
Dyspepsia
Dysmotility-like Symptoms Dominant
Educate/lifestyle modification
Trial of prokinetic medication
Success
Failure
Investigate
Continue with cyclic therapy
Test H. pylori
Gastroscopy or UGI

-
Eradicate
Consider H2 antagonists, tricyclics
Success
Failure
58
Rationale for the Use of Prokinetic Agents in
Dysmotility-like Functional Dyspepsia
  • Accelerate gastric emptying
  • Increase antral contractions
  • Decrease duration of proximal gastric distention
  • Antinausea

59
Placebo-controlled Trials of Prokinetic Agents
in Functional Dyspepsia
  • Of 11 trials with domperidone, 10 showed
    domperidone better than placebo
  • Of 19 trials with cisapride, 15 showed cisapride
    better than placebo

60
Placebo-controlled Trials of H2 Blockers in
Dyspepsia
  • Only 4 of 12 trials showed benefit vs. placebo
  • Overall, 59 response rate for H2 blockers, 48
    for placebo

61
Suggested Approach for Management of Dyspepsia
Dyspepsia
Initial interview and examination
Structural disease or alarm symptoms
Functional dyspepsia
Dysmotility-like symptoms dominant
Ulcer-like symptoms dominant
Education/lifestyle modification
Education/lifestyle modification
Test Hp

-
Eradicate
Trial of acid suppression
Trial of prokinetic medication
Success
Fail
Fail
Fail
Success
Success
Investigate/refer
62
Summary
  • Dyspepsia is common
  • On clinical grounds, functional dyspepsia can be
    separated into ulcer-like and dysmotility-like

63
Summary (contd)
  • Patients with ulcer-like functional dyspepsia
    should be tested for Helicobacter pylori, and
    treated accordingly
  • For patients with dysmotility-like functional
    dyspepsia, prokinetic drugs are effective

64
Case Presentation
  • 34 y.o. security guard
  • 5 years of intermittent epigastric discomfort
  • Bloating, postprandial nausea
  • Smokes, drinks 3 beers/day, 4 coffees/day

65
  • Ranitidine prescribed one year ago
  • - Initially beneficial, not now
  • Family history of peptic ulcer
  • Examination is normal

66
  • Can a diagnosis be made, based on history and
    examination?

67
  • You suspect functional dyspepsia
  • The patient requests investigation (worried about
    cancer or infection)

68
  • What investigations would you do?
  • What management suggestions would you make?
  • Would you suggest any medication?
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