The document discusses the management of uninvestigated dyspepsia in primary care settings. It finds that 15-25% of the general population experiences dyspepsia within a 12-month period. For patients presenting with uninvestigated dyspepsia, the recommendations are to first exclude other potential causes, then investigate those over age 50 or with alarm features and treat NSAID users accordingly. Younger patients without alarm features may be given a trial of empiric therapy or tested for H. pylori infection first before further investigation or treatment. Noninvasive H. pylori stool antigen testing is preferred over serology for detection.
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Evidence-Based Approach to Managing Uninvestigated Dyspepsia
1. An Evidence-based Approach
to the Management of
Uninvestigated Dyspepsia
in the Primary Care Settings:
an update
2. Dyspepsia:
the size of the problem
15–25% of the general population experience
dyspepsia within a 12-month period
Much more common than peptic ulcer
Up to 5% of primary care visits are due to dyspepsia
Most patients have no detectable abnormality on
radiological upper GI series or endoscopy
Endoscopy findings and symptoms do not correlate
Talley, J Clin Gastroenterol 2001; 32: 286–93.
Locke, Ballieres Clin Gastroenterol 1998; 12: 435–42.
Paré, Can J Gastroenterol 1999; 13: 647–54.
van Bommel et al., Postgrad Med J 2001; 77: 514–18.
Talley et al., BMJ 2001; 323: 1294–7.
3. Dyspepsia covers a range of symptoms
DYSPEPSIA
GERD PAIN OR DISCOMFORT IBS
centred in upper abdomen
UNINVESTIGATED INVESTIGATED
FUNCTIONAL
ORGANIC (or idiopathic)
(use of the term ‘non-ulcer’
is discouraged)
Talley et al., Gut 1999; 45(Suppl II): II37–42.
4. Definition of dyspepsia (Rome II)
Pain or discomfort occurring
centred in the upper abdomen
Talley et al., Gut 1999; 45(Suppl II): II37–42.
Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
8. Definition of Functional Dyspepsia (Rome II)
Twelve weeks or more (within the last 12
months) of persistent or recurrent dyspepsia
and evidence that organic disease likely to
explain the symptoms is absent
(including at upper endoscopy)
Dyspepsia subgroups
● Ulcer-like (predominantly pain)
● Dysmotility-like (predominantly discomfort)
● Unspecified (non-specific, no predominant symptom)
Talley et al., Gut 1999; 45(Suppl II): II37–42.
Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
9. Definition of Functional Dyspepsia
(Rome III)
At least 3 months, with onset at least 6 months
previously, of 1 or more of the following:
• Bothersome postprandial fullness
• Early satiation
• Epigastric pain
• Epigastric burning
And
• No evidence of structural disease (including at upper
endoscopy) that is likely to explain the symptoms
11. Uninvestigated Dyspepsia
Patient with new onset or recurrent
dyspeptic symptoms in whom no
investigation have been conducted
and no specific diagnosis for the
current symptoms exist
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
12. Uninvestigated dyspepsia
vs functional dyspepsia
Uninvestigated dyspepsia
● All symptomatic patients,
regardless of whether a cause
has been sought
Functional dyspepsia
● Symptomatic patients in whom
an organic cause has been
sought and excluded
Talley et al., Gut 1999; 45(Suppl II): II37–42.
14. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
- Other
Treat as appropriate
First Visit
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
15. Recommendation
Exclude other possible causes of the dyspeptic symptoms with
thorough history-taking and physical examination
Consider:
cardiac and hepatobiliary sources
medication-induced symptoms
possible dietary indiscretion
lifestyle or other causes
(grade C recommendation, consensus)
16. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
No - Other
(B)
Age >50 or alarm features? Treat as appropriate
- Vomiting
- Bleeding anemia YES
- Abdominal mass/ Investigate
unexplained weight loss
- Dysphagia
(endoscopy recommended)
First Visit
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
17. Older patients and with alarm features
America > 45 years
Canada > 50 years
Indonesia > 55 years
Cancer is a rare cause of dyspeptic symptoms
<2%
18.
19.
Diagnostic test: endoscopy or radiography?
Radiography : 70 %
Endoscopy : 96 %
Dooley et al., Ann Intern Med 1984;
101: 538-45
20. Specialist management of
uninvestigated dyspepsia
Endoscopy with biopsies
and
treat accordingly!
Talley et al., BMJ 2001; 323: 1294–7
21. Recommendation
Prompt investigation is recommended for patients over 50 years of age
with uninvestigated dyspepsia and for any patient presenting with alarm
features
Alarm features:
persistent vomiting
evidence of gastrointestinal bleeding or anemia
presence of an abdominal mass
unexplained weight loss
dysphagia
(grade B recommendation, level III evidence)
Endoscopy is the recommended method of investigation for patients
with uninvestigated dyspepsia who are over 50 years of age or who have alarm
features
(grade A recommendation, level II evidence)
22. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
No - Other
(B)
Age >50 or alarm features? Treat as appropriate
- Vomiting
- Bleeding anemia YES
- Abdominal mass/ Investigate
unexplained weight loss
- Dysphagia
(endoscopy recommended)
First Visit
NO
(C)
YES
NSAID and/or
Regular ASA NSAID Management
Use?
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
23.
Patients who use NSAIDs
Hp infection is the most common cause of
peptic ulcers
NSAIDs are responsible for most
Hp-negative ulcers
24. Recommendation
Patients with uninvestigated dyspepsia
who are regular users of NSAIDS
(including ASA) should be identified,
and if there are no alarm features,
they can be managed without initial endoscopy
(grade C recommendation, consensus)
25. NSAID and/or
reguler ASA use
YES
Can NSAID/ASA
Stop therapy
be stopped?
YES
NO
Patient improved? End
Treat or investigate NO
a. PPI
b. Cytoprotective agent
c. High-dose H2-RA
d. Switch to COX-2 inhibitor
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
26. Recommendation
If possible, NSAID use should be stopped
and the patient’s response monitored
(grade C recommendation, level III evidence)
If NSAIDs cannot be stopped the choice is to treat or investigate
Treatment recommendations for patients aged 50 years or less who
present with uninvestigated dyspepsia, who no alarm features and
who need to use NSAIDs (including ASA) are as follows:
• PPI
• Cytoprotective agent
• High-dose H2–RA therapy
(d) Consider switch to COX-2 inhibitor
(grade C recommendation, consensus)
27. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
No - Other
(B)
Age >50 or alarm features? Treat as appropriate
- Vomiting
- Bleeding anemia YES
- Abdominal mass/ Investigate
unexplained weight loss
- Dysphagia
(endoscopy recommended)
First Visit
NO
(C)
YES
NSAID and/or
Regular ASA NSAID Management
Use?
NO
(D) YES
Is dominant symptom
heartburn and/or Treat as reflux
regurgitation ?
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
28. Patients with dominant symptom of heartburn
or acid regurgitation, or both
Heartburn (89 %) or acid regurgitation (95 %) have
high specificity for GERD
Initial treatment can be started based on symptoms
of reflux in primary care
Most GERD patients do not have macroscopic
esophagitis
Endoscopy is not a useful diagnostic gold standard for
GERD, nor 24-hour pH monitoring
A reliable interpretation of the term heartburn is key
for the diagnosis of GERD
29. Recommendation
Patients aged 50 years or less with uninvestigated dyspepsia
and dominant symptoms of heartburn or acid regurgitation,
or both should be diagnosed as having GERD
and be treated accordingly
Rather than using the term “heartburn”, describing the
sensation of “a burning feeling rising from your stomach
or lower chest toward your neck” increases the
diagnostic accuracy for GERD
(grade B recommendation, level II-2 evidence)
30. Reflux mini-management schema
Dominant symptom heartburn and/or regurgitation
Treat
a. PPI
b. H2-RA
c. Prokinetic
Reassess at 4 weeks
Symptoms
YES
Resolved?
NO
Treat
- If not on PPI, switch to PPI x 4-8 weeks
- If on PPI, double dose x 4-8 weeks or
consider investigation
Symptoms YES Stop therapy (if symptoms recur,
resolved? repeat original therapy)
NO
Investigate Sander et al., CMAJ 2000; 162 (Suppl): S1–23
31.
Management of patients with GERD
Five treatment possibilities for GERD
- lifestyle modification
- antacids
- H2RAs
- prokinetic
- PPIs
Review of lifestyle modification and antacids concluded
that definitive evidence of efficacy is unavailable
Milder symptoms of GERD may derive benefit from
lifestyle modification
32. Recommendation
The effectiveness of lifestyle modifications and antacids for the treatment
of GERD is not proven. Patient with mild GERD symptoms may derive
benefit from these treatment
(grade C recommendation, consensus)
Treatment recommendations for patients with a dominant symptom of
heartburn or acid regurgitation, or both, are as follows :
• PPI
(a) H2 – RA
(b) Prokinetic agent
(grade A recommendation, level I evidence)
Patients should be reassessed after 4 weeks of therapy
(grade C recommendation, consensus)
33. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
No - Other
(B)
Age >50 or alarm features? Treat as appropriate
- Vomiting
- Bleeding anemia YES
- Abdominal mass/ Investigate
unexplained weight loss
- Dysphagia
(endoscopy recommended)
First Visit
NO
(C)
YES
NSAID and/or
Regular ASA NSAID Management
Use?
NO
(D) YES
Is dominant symptom
heartburn and/or Treat as reflux
Regurgitation ?
NO
(E)
YES
Hp test positive?
1. UBT Treat as Hp positive
2. Serology
34. Hp test and treat strategy
Hp infection is associated with
- duodenal ulcer 90 – 95 %
- gastric ulcer 60 – 80 %
- gastric cancer
Uncertainty as to whether Hp plays a role in
dyspepsia in the absence of ulcers
Option for the treatment of younger patients w/o alarm features:
- trial of empiric (antisecretory or prokinetic)
- diagnostic evaluation
- non invasive testing for Hp
followed by eradication therapy for patients w/ (+)ve results
- non invasive testing for Hp
followed by endoscopy for patients w/ (+)ve results
35. Recommendation
A test-and-treat strategy for uninvestigated dyspepsia
in younger patient (aged 50 years or less)
who have no alarm features is recommended
(grade B recommendation, level I evidence)
36.
Testing for Hp infection
Infection can be detected by:
- invasive (endoscopy based)
- non invasive (UBT, HPSA or serologic
testing)
Serologic testing cannot be used to determine cure
as the IgG antibodies remain detected for a long
time after eradication
UBT has a high (+)ve and (-)ve predictive value
(both > 95 %)
Gisbert et al. Aliment Pharmacol Ther 2004;20:1001–17
37. Recommendation
Noninvasive methods are recommended
for the detection of H. pylori in patient aged 50 years or less
with uninvestigated dyspepsia who have no alarm features
Hp stool antigen is the preferred test
(grade B recommendation, level II-2 evidence)
38. Recommendation
No more serology
Stool antigen is the recommended test
Test with stool antigen before prescribing
PPIs
do not have alarm symptoms
have not been using NSAIDS
who are not > 55 yrs
(AGA guidelines from 2005)
39. H. Pylori positive mini-management schema
Patient Hp positive
Eradicate Hp:
a. PPI + AC or MC or
RBC + AC or MC (bid x 7 days)
b. Alternative first line therapy
c. PPI + BMT (bid x 14 days)
(advise patient to return 4 weeks after
treatment if symptoms recur or persist)
YES
Symptoms No further therapy
resolved at follow up? or investigation
NO
Confirm Hp eradication by UBT
or histology (not serology)
YES
Hp eradicated? Treat as Hp negative
NO
Switch regimen and retreat
or refer for investigation
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
40. Hp eradication therapy
(a) First line therapy
PPI + AC or PPI + MC (bid for 7 days)
or ranitidine bismuth citrate + AC or MC
• Alternative first-line therapy
• PPI + BMT (14-day quadruple regimen)
PPI (bid)
B (4x2 tablets/day)
M (4x250 mg/day)
T (4x500 mg/day)
PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg
A = Amoxicillin 1000 mg
B = Bismuth subsalicylate (2 tablets)
C = Clarithromycin 250 (or 500 mg if treatment failure)
M = Metronidazole 500 mg (250 mg in BMT combination therapy)
T = Tetracyclin 500 mg
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
41. Recommendation
Eradication therapies recommended for patients
with uninvestigated dyspepsia who are found
to be H. pylori positive are as follow:
• PPI + AC or MC,
or ranitidine bismuth citrate + AC or MC
• Alternative first-line therapy
(c) PPI + BMT
PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg
A = Amoxicillin 1000 mg
B = Bismuth subsalicylate (2 tablets)
C = Clarithromycin 250 (or 500 mg if treatment failure)
M = Metronidazole 500 mg (250 mg in BMT combination therapy)
T = Tetracyclin 500 mg
(grade A recommendation, level I evidence)
42. A meta-analysis of short versus long therapy
with a PPI, clarithromycin
and either metronidazole or amoxicillin
for treating Hpinfection
A meta-analysis of 13 studies:
Eradication rate for 14-day therapy vs 10-day therapy
was 81% (95% CI, 77%–85%) vs 72% (95% CI, 68%–76%)
The eradication rate for 10-day therapy vs 7-day therapy:
83% (95% CI, 75%–89%) vs 80% (95% CI, 71%–86%)
Calvet et al. Aliment Pharmacol Ther 2000;14:603–609
43. Meta-analysis:
duration of first-line PPI-based triple therapy
for Helicobacter pylori eradication
Extending triple therapy beyond 7 days
is unlikely to be a clinically useful strategy
Fuccio et al. Ann Intern Med. 2007;147(8):553-62
44. Pantoprazole based therapies in HP eradication:
a systematic review and meta-analysis
Pantoprazole achieves similar cure rates to
those of omeprazole and lansoprazole
when co-prescribed with antibiotics
Eur J Gastroenterol. 2004;16: 89-99
45. Uninvestigated Dyspepsia Consider :
- Cardiac
- Hepatobiliary
(A) YES
- Medication-induced
Other possible causes ? - Dietary indiscretion
No - Other
(B)
Age >50 or alarm features? Treat as appropriate
- Vomiting
- Bleeding anemia YES
- Abdominal mass/ Investigate
unexplained weight loss
- Dysphagia
(endoscopy recommended)
First Visit
NO
(C)
YES
NSAID and/or
NSAID Management
Regular ASA
Use?
NO
(D) YES
Is dominant symptom
heartburn and/or Treat as reflux
Regurgitation ?
NO
NO
(E)
YES
Treat as Hp Negative Hp test positive?
Treat as Hp positive
1. UBT
2. Serology Sander et al., CMAJ 2000; 162 (Suppl): S1–23
46. H. Pylori negative mini-management schema
Patient Hp negative
Treat x 4 weeks
a. PPI
b. H2-RA
c. Prokinetic
YES
Symptoms
resolved?
NO
Modify therapy
(increase dose or switch to another therapy)
YES
Symptoms
resolved? Stop
NO
therapy
Reassess or investigate/refer
Sander et al., CMAJ 2000; 162 (Suppl): S1–23
47. Recommendation
There is good evidence that antacids are ineffective
for functional dyspepsia, and they are not recommended
for the treatment of uninvestigated dyspepsia
in patients subsequently found to be H. Pylori negative
(grade B recommendation, level I evidence)
48. Recommendation
Treatment recommendation for patients who present
with uninvestigated dyspepsia and who subsequently
have negative results of testing for H. Pylori are as follows:
(a) PPI
(b) H2-RA
(c) Prokinetic agent
(grade B recommendation, level I evidence)
49. Summaries
Clinical management tool consists of 5 key steps in
the evaluation of patients with uninvestigated
dyspepsia
The tool includes 4 mini-management schemata
The tool is practical, easy to use, explicit and concise,
and it reflects the realities of the primary care setting
Adoption of this tool will optimize the treatment of
patients with dyspepsia, improve quality of care and be
cost-effective
50. PRIMARY MANAGEMENT OF NEW ONSET
UNINVESTIGATED DYSPEPSIA IN INDONESIA
EXCLUDE BY HISTORY : IF < 2 – 4 WKS.
DYSPEPSIA DIETARY ADVICE, OBSERVE
BILLIARY PAIN,
IRRITABLE BOWEL, REFLUX REVIEW CURRENT MEDS.
AGE > 55 YRS AGE > 55 YRS
WITHOUT ALARM FEATURES
WITH ALARM FEATURES :
SEVERE VOMITING
FEVER
TREATMENT TRIAL : 2 WKS SUCCESS HEMATEMESIS / MELENA
ANTACIDS
ANTISECRETORY ICTERUS
↓ BW
PROKINETICS NSAIDs
FOLLOW UP STRONG FEAR OF SERIOUS DIS.
FAILURE OR
EARLY RELAPSE FAMILY HISTORY : GASTRIC CA.
RELAPSE
SEROLOGIC Hp TESTING SPECIALIST REFFERAL :
GASTROENTEROLOGIST
NEG. POS. INTERNAL MED./PED. WITH
ENDOSCOPIC FACILITIES
FINAL EVALUATION AFTER 8 WKS
> 3 X RELAPSE
Editor's Notes
Dyspepsia – whatever the cause – is common in the general population, and is more common than peptic ulcers. Dyspepsia affects up to a quarter of the population in a 12-month period. Up to 5% of primary care consultations are due to dyspepsia.
The pain of dyspepsia overlaps with that of GORD and irritable bowel syndrome (IBS). Functional dyspepsia is a diagnosis that can only be made after investigation to exclude an organic cause. It is not necessary to investigate all patients with dyspepsia. Use of the term ‘non-ulcer’ dyspepsia is now discouraged.
According to Rome II criteria, dyspepsia is any pain or discomfort occurring in the upper abdomen. Dyspepsia is further divided into subgroups on the basis of the predominant symptom (ulcer-like, dysmotility-like and non-specific) rather than symptom clusters. While proposed for research purposes, these dyspepsia subgroups are not particularly useful in clinical practice in providing clues to the underlying disease, and therefore, remain contentious.
All of the diseases on this slide are related to inappropriate amounts of acid/levels of acid secretion in the various regions of the upper gastrointestinal (GI) tract. These are the primary areas dealt with in this slide kit.
Patients with dyspepsia may have underlying organic lesions Among patients diagnosed as having dyspepsia, 60–80% may have underlying organic lesions. Reflux esophagitis is frequently the most common such lesion, occurring in up to 1 in 4 dyspeptic patients. 23-25 In a group of 3667 primary care patients in the UK with a clinical diagnosis of dyspepsia, over 60% were subsequently diagnosed endoscopically as having an organic lesion, and over 20% of the dyspeptic patients had reflux esophagitis 25 . However, given the prevalence of dyspepsia, it is not feasible to refer all patients for endoscopy, and the physician has to make a decision on who should be treated empirically and who should receive further investigation.
Dyspepsia has been classified into subgroups based on medical history Dyspeptic patients have been divided into clinical subgroups based on their medical history to try to match symptoms with pathophysiological disturbances and thus enable rational prescribing. The subgroups include those with ulcer-like (typical ulcer symptoms), reflux-like (retrosternal and concomitant upper abdominal symptoms), dysmotility-like (symptoms suggestive of gastric stasis) and unspecified (those whose symptoms cannot be classified) dyspepsia 5 . For any individual patient, however, the symptom pattern may change over time 21 . In addition, considerable overlap exists between the subgroups and few patients exhibit symptoms exclusive to one particular group 3, 22 . For example, in an endoscopy-based study of patients diagnosed with dyspepsia, the prevalence of peptic ulcer disease was found to be similar among patients regardless of whether they had reflux-like (11%), ulcer-like (9%) or dysmotility-like dyspepsia (7%) 22 .
Functional dyspepsia is a diagnosis that can only be made after investigation. Patients with functional dyspepsia (non-organic dyspepsia) have undergone investigation, such as upper GI barium series or upper GI endoscopy, at which time an ulcer (an organic cause of the pain/discomfort) has not been observed. It is not necessary to investigate all patients with dyspepsia, but it is important to take a careful history to rule out the more obvious serious differential diagnoses.
Specialist investigation usually takes place after one or more therapeutic trials with antisecretory agents have been carried out in general practice. Endoscopy and biopsy is used to rule out possible organic causes for the pain.