Transcript Refractory GERD

Refractory GERD
Khalil HONEIN, M.D.
Gastroenterology – Hôtel Dieu De France
Introduction
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GERD: Symptoms or mucosal damage
due to abnormal reflux of gastric
contents into esophagus
Refractory GERD: GERD symptoms or
esophagitis despite treatment with PPI
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Patients requiring more aggressive therapy
Patients having other causes of S
Failure of treatment with PPI
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Efficacy of PPI is dose dependant
Likelihood of healing esophagitis:
proportional to fraction of day with
intra-gastric pH above 4
Factors contributing to
inadequate PPI response
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Nocturnal Acid Breakthrough (NAB)
Reduced bioavailability
Effect of food and dosing interval
Differences in metabolism
Gastric acid hypersecretion
HP status
Drug resistance, slow healing
Nocturnal Acid Breakthrough
(NAB)
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May be responsible for majority of patients
with refractory GERD
Up to 70% of patients taking PPI twice
daily will have periods of gastric pH<4
lasting for more than 1 hour(at night)
Esophageal acid exposure higher in
patients with GERD and correlated with
severity of esophagitis
Katz Po et al. Aliment Pharmacol Ther 1998;12 :1231
Nocturnal Acid Breakthrough
(NAB)
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Nocturnal acid exposure while on PPI
May be reduced by H2RA and by
increasing PPI dose
Sometimes difficult to eliminate
Ours, Am J Gastro 2003;98 :545-50
Reduced Bioavailability
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Bioavailability of PPI influenced by
environmental and manufacturing conditions
For most patients, difference in bioavailability
are not clinically significant
Acid secretion decrease similar with lanzo or
omeprazole
Andersson T. Br J Pharmacol 1990; 29:557
Dammann HG. Aliment Pharmacol Ther 1997; 11:359
Effect of food and dosing
interval
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Administration 15-30 min prior to
meals, particularly in refractory patients
(individual variability)
Brummer RJ. Dig Dis Sci 1997; 42 :2132
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PPI usually given once daily and
sometimes twice daily improve gastric
acid suppression
Kuo B. Am J Gastroent 1996; 91 :1532
Differences in metabolism
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PPI metabolized through the CYP 2C
Genetically- determined variability may
↓ effect on gastric acidity
CYP 2C absent:
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3% of Caucasian patients
in more than 10% in Asians
Gastric acid hypersecretion
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Patients with BAO > 10mEq/h may
predisposed to refractory GERD
Should be considered in refractory
patients
Collen MJ. Dig Dis Sci 1994; 39 :1434
HP status
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Role not established in refractory
patients to adequately –dosed PPI
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No evidence that eradication
exacerbates GERD
Fallone Aliment Pharm Therapy 2004;20(7) : 761-768
Drug Resistance
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Resistance is a rare condition caused by
mutations of the PP
Patients can be treated by H2RA
Endoscopic healing and Σ relief: achieved
within 8 weeks
Severe esophagitis take longer to heal
Leite L. Gastroenterology 1995; 108:A147
Chiba N. Gastroenterology 1997;112 :1798
OTHER CAUSES OF
SYMPTOMS
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Other pathological situations
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Esophageal hypersensitivity
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Non acid reflux
(Patients still Σ despite adequate acid
supression)
Other Pathological Situation
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IBS and dyspepsia with overlap Σ
Atypical GERD ( cough, asthma, NCCP )
Achalasia
Cancer or stricture
Caustic and Infectious esophagitis
NSAID ( more susceptibility to acid
related E disease)
Sopena. J clin Gastro 1998; 27:316
Losurdo. Gastroenterology 1999; 116: A 239
Esophageal Hypersensitivity
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To physiologic acid reflux ( visceral
hyperalgesia)
Trimble KC. Dig Dis Sci 1995; 40:1098
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Patients with heartburn but without
endoscopic or pH evidence of GERD
Acid suppressive therapy and low dose
antidepressants
Rodriguez Am J Gastroenterol 1999; 94:628
Trimble Study
Dig Dis Sci 1995; 40:1098
Group A
Group B
Number
70
58
GERD Σ
Normal pH
metry
87%
Excess reflux
on pH metry
79%
Σ patients
up 4-5 years )
(follow
Patients taking 60%
PPI
60%
Non Acid Reflux
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Mixed acid and bile refluxate (more
aggressive than acid alone)
DGER: in patients with gastric surgery
Bilitec Test: Spectrophotometric detection of
bilirubin concentration
Combined pH and Bilitec > pH alone for
detection of pathological reflux in refractory
patients
Tack J. Am J Gastro 2004; 99:981
Yumiba T. Am J Gastro 2002; 97 :1647
Bilitec
Bilitec
Non Acid Reflux
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Impedance Monitoring
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Measure simultaneously reflux of alkaline
or acid refluxate
Discern reflux of gas from liquids
Advantage in patients
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with high suspicion Σ of GERD
but non significant IS at 24 h pH metry
Des Varannes. Congrès Francophone 2004, p208-216
Vela. Gastroenterology 2001; 120:1599-606
Non Acid Reflux
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Esophageal pH -Impedancemetry
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Gold standard for GERD diagnosis
Allows detection of non acid Σ episod
reflux in 1/3 patients with N standard pH
metry
Sifrim Gut 2004; 53.7;1024-31
DesVarannes GCB Mars 2005; A124
Non acid reflux
Serraj (Motility) Lyon France, Juin 2005
33 patients
Group 2 without
PPI: 73 patients
24H % acid reflux
9.6%
48%
Non acid reflux
87%
34%
% time under pH 4
91%
67%
IS
44%
64%
Group 1 on PPI:
Recommandations
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GERD refractory to an adequate medical therapy is
rare
Dg carefully confirmed with esophageal pH impedancemetry
Dg must be sometimes reconsidered:
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ambulatory pH- impedancemetry, either on or off therapy
additionnal endoscopic& manometric evaluations
testing& therapeutic trials for other considerations
Keneth R ( Practice guidelines) Am J Gastro 2005; 100:190-200
Treatment
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Medical treatment
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Endoscopic treatment
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Surgical therapy
Medical treatment
Why has patient not responded to PPI?
 Inadequate therapy
 Non reflux causes of esophagitis
 Esophageal hyperalgesia
 Non acid reflux
Kahrilas JP. Gastroenterology 2003; 124:1941-4
Medical treatment
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Adjust PPI dose
Therapeutic trial used as a dg test
Patients with acid related S should
respond to a PPI
Some require higher dose of PPI
Failure of high dose therapy suggest
non acid Σ
Devault Am J Gastroent 1999; 94: 1434-42
Medical treatment
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Give PPI twice daily
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PPI dose before dinner may reduce NAB
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PPI 15-30 min before meals
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Stepwise increase dose of PPI to achieve
adequate acid suppression
Fass R. Gastroent 2004; 126:A 37
Medical treatment
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An increase in dose of Ome to 80 mg/ day→
significant decrease in acid secretion (Vs 20
mg bid) (pH<4: 33% vs 74%)
Addition of a nighttime dose H2RA to control
NAB
H2RA not as effective as PPI for maintenance
therapy
Orr. Alim Pharmacol Therapy 2003; 17: 1553
Fackler Gastroenterology 2002;122:625
Medical treatment
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Effectiveness of adding prokinetic drug not
established
Switching to another PPI for patients refractory to
one PPI ( rare mutations in the PP induce resistance)
Add Baclofen (GABA-B agonist )
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Effective to treat GERD with chronic cough
Inhibits TLESR
With Esome both decrease total acid and non acid reflux
Peterson K. Am J Gastroent 2005, vol 100,9,S40
Vela M. Am J Gastroent 2005, vol 100,9,S43
Endoscopic treatment
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Endoscopic techniques ( radiofrequency
application to LES, endoscopic sewing
technique, or injection into LES area)
Improve reflux symptoms but:
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Significant changes in LESp not
documented
Less than 35% of patients demonstrated to
have a normalization of their
intraesophageal acid exposure
Endoscopic treatment
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Many issues remain unresolved:
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long term durability and safety
efficacy of these procedures performed
outside of clinical trials
efficacy in atypical presentations of GERD
Kenneth R. Am J Gastrenterol 2005; 100:190-200
Surgical treatment
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To be considered when:
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young patients require high dose of PPI
unwelling to take or intolerant patient
failed medical therapy with persistent Σ
esophagitis
persistent Σ due to nocturnal regurgitations(
asthma, laryngitis)
recurrent Σ relapse after discontinuing therapy
Fack KM. J Gastro Hepato 2004; 19:357-67
Take Home Message
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Assure compliance, and eliminate aggravating factors
Increase dose of PPI
Role of NAB ( add H2RA at night)
Endoscopy documents esophagitis(dg GERD &r/o
nonacid causes)
ENRD does not rule out acid as a cause of S
PH- Impedance testing identifies S nonacid reflux
Surgery may be appropriate but many patients need
continued medical therapy
Endoscopic treatment for highly selected patients,
but lack of long term results.
Acid Reflux Sumptoms
PPI test
Response
GERD
No response
Trial of PPI bid
EGD
Erosive esophagitis
Negative endoscopy
Adjust PPI dose
24 hour pH probe
Positive
Negative
Adjust PPI dose
Other causes
Thank You