Patients dosed suboptimally the PPIs(%)
>60 min before meals 39%
after meals
30%
Hale Waihona Puke at bedtime28%
as-needed
4%
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Psychological
Weakly acid ref lux
Poor compliance
with PPI treatment
Mechanism
NAB
Dilated intercellular
spaces
Gastroparesis
Esophageal hypersensitivity
DGER
7
Potential factors contributing to the spectrum of reflux perception in patients with GERD
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Esophageal receptor upregulation and/ or enhanced signaling
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES ，2008，22 （11） 2440-2444
10
Poor Compliance with PPI Treatment
?Compliance to treatment and proper dosing are important. ?Timing and frequency of dosing are critical for maximum
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4
NERD-acid,visceral sensitivity
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5
Potential causes of PPI refractoriness in GERD
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Neurogastroenterol Motil (2012) 24, 697–704 6
Gastroparesis, concomitant in 25% of patients with gastroesophageal reflux disease (GERD), has been shown to improve after Nissen fundoplication.
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—Richter JE Natl Clin Gastroenterol 2007;4:658
? Others suggest that lack of satisfactory symptomatic response to PPI once a day is suf?cient to consider patients as PPI failures.
Failure on PPI qd 6-15%
Barrett′s oesophagus 6-10%
Failure on PPI qd 20%
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——Fass et al. Aliment Pharmacol Ther 2005; 22(2):739-94.
30%NERD fail to PPI treatment
Physiological stressors, sensitization of spinal sensory neurons
AM J Gastroenterol ,2012, 107, 89-15.
Gastroparesis
Delayed gastric emptying (gastroparesis) may be a factor associated with severe reflux, dyspepsia, or both.
ef?cacy of the medication.
PPI dosing situation in 100 patients with persistent GERD symptoms
Patients dosed
Proper dosing timing 46%
optimally the PPIs(%)
? Any attempt to narrow the de?nition of refractory GERD might exclude many true sufferers.
——Hershcovici T et al. Best Practice& Research Clinical Gastroenterology 2010 (24)923-936
Weakly Acid Reflux
? The prevalence of weakly acidic reflux in refractory GERD is 30-40%.
? When the esophageal pH falls by ≥ 1 unit, but remains ＞4, it is considered “weakly acidic reflux”.
Remains an area of controversy
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2
PPI failed in Each of the Gastrooesophageal Re?ux Disease (GERD) Groups
GERD
NERD 60-70%
EE 20-30%
Failure on PPI qd 40-50%
? Esophageal distension
? Persistent impaired mucosal integrity
? Esophageal hypersensitivity
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Gut,2004,53:1024-18031
Esophageal Hypersensitivity
1
Definition of RGERD
? RGERD:Patients who are unresponsive to 4-8 weeks' treatment with PPIs twice daily or esophageal injury caused by RE can't to be healing.