Castell_edit.qxp 4/10/07 10:22 am Page 69
Clinical Importance of Non-acid Reflux
multicenter study, this figure was 35%, with an additional 8% having In a proof-of-principle study we found that a single dose of baclofen
symptoms with continued acid reflux using the symptom index (SI) as 40mg orally led to a significant reduction in both acid and non-acid reflux
diagnostic finding.
10
These results were supported in a European study by episodes in both healthy volunteers and GERD patients.
16
Using a
a French–Belgian consortium in which 60 patients were studied on PPI stepwise increase in the dose of baclofen, Koek et al. reported the
therapy and 32% had a positive symptom association probability (SAP) efficacy of this compound in controlling duodenal-gastro-esophageal
for non-acid reflux, with an additional 20% having symptoms associated reflux and symptoms in a group of 16 patients with persistent reflux
with acid reflux.
11
The authors of this study commented that
regurgitation and cough were the symptoms most frequently associated
with non-acid reflux. Of note is that in both studies the most frequent
We have frequently emphasized
finding was that the persistent symptoms were not associated with any
kind of reflux. In our experience, this ‘negative’ finding is extremely
consideration of ‘reflux-reduction’
helpful in the subsequent care of the patient, since it directs further
therapies for patients on proton pump
diagnostic efforts toward seeking a diagnosis other than GERD.
inhibitor therapy in whom multichannel
Management of Symptomatic Non-acid Reflux
intraluminal impedance–pH has shown
We have frequently emphasized consideration of ‘reflux-reduction’
therapies for patients on PPI therapy in whom MII–pH has shown
symptoms to be related to non-acid
symptoms to be related to non-acid reflux. This is now supported in
reflux. This is now supported in
recent publications. A study evaluating clinical response following
laparoscopic Nissen fundoplication in a group of patients with positive SI
recent publications.
for either acid or non-acid reflux during pre-operative MII–pH monitoring
on twice-daily PPIs found a 94% success rate after an average follow-up symptoms, normal pH monitoring, and pathological Bilitec
®
monitoring
of 15 months.
12
A similar result has been shown in patients with chronic during PPI treatment. While the side effects of baclofen limit its clinical
cough in whom SI was positive for non-acid reflux.
13
In addition, a recent use, currently available data indicate that pharmacological agents
publication from Belgium also suggested that non-acid reflux is a decreasing the frequency of tLESRs can be used as reflux-reduction
potential mechanism for chronic cough, and that this can be agents to control symptomatic non-acid reflux.
demonstrated using combined MII–pH monitoring.
14
Summary and Conclusions
Currently available pharmacological ‘reflux-reduction’ agents include The primary focus in GERD has been on acid-induced gastroesophageal
compounds that decrease the frequency of transient lower esophageal lesions. Highly potent acid-suppressive therapy using PPI therapy has
relaxations (tLESRs). Baclofen, a gamma-aminobutyric acid type b been efficient in healing esophageal lesions. Still, approximately 30–35%
(GABAb) agonist, acts centrally by inhibiting the medullar centers of patients on PPI therapy report residual symptoms. Studies using
involved in tLESR reflexes. Ciccaglione and Marzio performed a double- combined MII–pH monitoring documented that in approximately 40% of
blind, placebo-controlled study evaluating the ability of baclofen to patients with persistent symptoms on PPI therapy, these residual
decrease esophageal acid exposure (i.e. %time pH <4) in both healthy symptoms are associated with non-acid reflux. While the optimal
volunteers and GERD patients.
15
In addition, chronic use of baclofen treatment for symptomatic non-acid reflux is still under investigation,
(baclofen 10mg four times daily for four weeks) was superior to placebo current data suggest that medical and surgical interventions aimed at
in controlling not only distal esophageal acid exposure but also reflux augmenting the gastroesophageal barrier may be the most promising
symptom scores. reflux-controlling therapies. ■
1. Stanghellini V, Relationship between upper gastrointestinal gastroesophageal reflux, Clin Gastroenterol Hepatol, persistent reflux symptoms on acid suppressive therapy who
symptoms and lifestyle, psychosocial factors and comorbidity in 2007;5:172–7. benefit from a laparoscopic Nissen fundoplication, Br J Surg,
the general population: Results from the domestic/international 7. Sifrim D, Castell D, Dent J, Kahrilas PJ, Gastro-oesophageal 2006;93:1483–7.
gastroenterology surveillance study (DIGEST), Scand J reflux monitoring: review and consensus report on detection 13. Tutuian R, Mainie I, Agrawal A, et al., Non-acid reflux in
Gastroenterol Suppl, 1999;231:29–37. and definitions of acid, non-acid, and gas reflux, Gut, patients with chronic cough on acid-suppressive therapy.
2. Dent J, El-Serag HB, Wallander MA, Johansson S, Epidemiology 2004;53:1024–31. Diagnosis with impedance-pH monitoring and initial results of
of gastro-oesophageal reflux disease: A systematic review, Gut, 8. Velasco N, Pope CE, Gannan RM, et al., Measurement of fundoplication, Chest, 2006;130:386–91.
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4. Castell DO, Kahrilas PJ, Richter JE, et al., Esomeprazole (40mg) Hepatol, 2004;2:656–64. 15. Ciccaglione AF, Marzio L, Effect of acute and chronic
compared with lansoprazole (30mg) in the treatment of erosive 10. Mainie I, Tutuian R, Shay S, et al., Acid and non-acid reflux in administration of the GABA B agonist baclofen on 24 hour pH
esophagitis, Am J Gastroenterol, 2002;97:575–83. patients with persistent symptoms despite acid suppressive metry and symptoms in control subjects and in patients with
5. Vakil N, van Zanten SV, Kahrilas P, et al., Global Consensus therapy. A multicenter study using combined ambulatory gastro-oesophageal reflux disease, Gut, 2003;52:464–70.
Group, The Montreal definition and classification of impedance–pH monitoring, Gut, 2006;55:1398–1402. 16. Vela MF, Tutuian R, Katz PO, Castell DO, Baclofen decreases
gastroesophageal reflux disease: a global evidence-based 11. Zerbib F, Roman S, Ropert A, et al., Esophageal pH–impedance acid and non-acid post-prandial gastro-oesophageal reflux
consensus, Am J Gastroenterol, 2006;101:1900–20. monitoring and symptom analysis in GERD: a study in patients measured by combined multichannel intraluminal impedance
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intraluminal impedance and pH esophageal testing compared to 12. Mainie I, Tutuian R, Agrawal A, et al., Combined multichannel
pH alone for diagnosing both acid and weakly acidic intraluminal impedance-pH monitoring identifies patients with
US GASTROENTEROLOGY REVIEW 2007 69
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