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*Department of Internal Medicine, Faculty of Medicine, University of Indonesia/Dr. Cipto
Mangunkusumo General National Hospital, Jakarta
**Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine
University of Indonesia/Dr. Cipto Mangunkusumo General National Hospital, Jakarta
Corresponding author:
Marcellus Simadibrata. Division of Gastroenterology, Department of Internal Medicine, Dr. Cipto Mangunkusumo
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Keywords: UHIUDFWRU\ JDVWURHVRSKDJHDO UHÀX[ GLVHDVH *(5' SURWRQ SXPS LQKLELWRU 33, WKHUDS\
diagnosis, therapy, reevaluation
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Kata kunci: refractory GERD, terapi proton pump inhibitor (PPI), diagnosis, terapi, reevaluasi
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PPI trial Classic symptoms, no warning signs Meta-analysis Negative trial does not rule out GERD
Barium swallow Not for GERD diagnosis. Use for Case-control Do not use unless evaluating for complication
evaluation of dysphagia (stricture, ring)
Endoscopy Alarm symptoms, screening of high- risk Randomized control Consider early for elderly, those at risk for
patients, chest pain trial Barrett’s, non- cardiac chest pain, patients
unresponsive to PPI
Esophageal biopsy Exclude non-GERD causes for Case-control Not indicated for diagnosis of GERD
symptoms
Esophageal manometry Preoperative evaluation for surgery Observational Not recommended for GERD diagnosis. Rule
out achalasia/scleroderma-like esophagus
preop
$PEXODWRU\UHÀX[ Preoperatively for non-erosive disease. Observational &RUUHODWHV\PSWRPVZLWKUHÀX[GRFXPHQW
monitoring Refractory GERD symptoms,GERD DEQRUPDODFLGH[SRVXUHRUUHÀX[IUHTXHQF\
diagnosis in question
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Most of GERD patients did not respond to PPI also proven to improve GERD symptoms.23 Step by
therapy was from NERD and functional pyrosis step for refractory GERD treatment approach can be
group. Patients with NERD that response to PPI seen in following algorithm.
therapy only 37%. In contrast, ERD patients showed 7KH¿UVWVWHSLQUHIUDFWRU\*(5'WUHDWPHQWLVWR
a better response to PPI therapy, account for 56%.20 In reevaluate patient compliance during previous PPI
refractory GERD, etiology of PPI resistance should be
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GERD patients was compliance and previous therapy
strategy. PPI optimization, whether by dosage and
regiment compliance, should be done in refractory
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approach. Approach to refractory GERd diagnosis was
presented in Figure 1. Richter et al simplify refractory
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Based on previous theory, treatment of GERD
included medical and non-medical therapy. Life style
changes becomes important in this situation.
A systematic review reported that cocoa
consumption, tobacco, and soda will also reduce LES
competency, besides alcohol, caffeine, and fatty diets.22
But, several study comparing patients diets to GERD
diagnosis reported a contradictive result. High body
mass index increase GERD risk by several mechanism,
and reduce in body weight will improve GERD
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symptoms.6 Sleeping position with head elevation was ¿QGLQJV
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Weight loss Improvement of GERD symptoms Case-control Strong recommendation for patients with BMI >
and esophageal pH 25 or patients with recent weight gain
Head of bed elevation Improved esophageal pH and Randomized Head of bed elevation with foam wedge or
symptoms controlled trial blocks in patients with nocturnal GERD
Avoidance of late evening Improved nocturnal gastric acidity Case-control Avoid eating meals with high fat content within
meals but not symptoms 2-3 h of reclining
Tobacco and alcohol No change in symptoms or Case-control Not recommended to improve GERD
cessation esophageal pH symptoms
Cessation of chocolate, No studies performed No evidence Not routinely recommended for GERD
caffeine, spicy, foods, patients. Selective elimination could be
citrus, carbonated considered if patients note correlation with
beverages GERD symptoms and improvement with
elimination
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therapy. PPI therapy should be given 30 minutes before surgical therapy. On the other hand, negative test result
meals. Life style changes, have been mention above, was the indication for pain therapy (selective serotonin
should be emphasized to reach effective treatment reuptake inhibitors/SSRI or tricyclic antidepressant/
outcome.24 There are two options for patients that TCA). Positive result for acid may indicated the need
did not response to once daily PPI dosage, of which of therapy reevaluation. Reevaluation consist of PPI
double its dosage or change to the other PPI regiments. optimization, TLESR reducer, histamine antagonist
Doubling PPI dosage was the most commonly used receptor before sleep, and also surgical management.
treatment strategy by clinicians. American College of In healthcare service provider where esophageal
Gastroenterology said that both strategies options could impedance and pH-monitoring test was unavailable,
be used and proven to improve its outcome in reduce symptoms characteristic could be the reason to give
20% of heartburn symptoms.19,25 therapy. A dominant regurgitation symptoms indicated
Esophageal impedance and pH-monitoring, which the need of TSLER reducer therapy, while a dominant
can detect acid, weak acid, and alkaline, was the further heartburn symptoms indicated histamine-2 receptor
approach in patients that did not respond to double dose antagonist therapy before sleep. If this regiment did not
PPI therapy. This test was also detect the correlation of give an effective outcome, pain modulator such SSRI
V\PSWRPVWRUHÀX[DWHDQGDOVRLWVFKDUDFWHULVWLFJDV and TCA could be use. There were no evidence yet
liquid, and mixed). This test could identify different for giving antidepressant empirically in patients with
etiology of GERD, either by acid, weak acid, alkaline, refractory GERD.24
or functional pyrosis. A positive test result was the TSLER reducer showing the good outcome was
indication for TSLER inhibitor therapy, pain therapy, and GABA agonist such as baclofen. Adding 20 mg baclofen
three times per day together with omeprazole improves to reevaluate patient compliance during previous PPI
HVRSKDJHDOUHÀX[IUHTXHQF\S 17 Prokynetics therapy. Esophageal impedance and pH-monitoring,
therapy could be combined with PPI in patients with which can detect acid, weak acid, and alkaline, was
refractory GERD. Metoclopramide could increase the further approach in patients that did not respond
LES tonus, esophageal peristaltic, and reduce gastric to double dose PPI therapy. Surgical management as
emptying time. But there were no study yet to prove DQWLUHÀX[WKHUDS\ZDVHPHUJLQJLQWKHODVWGHFDGHV
that prokynetic given without gastroparesis in GERD Stretta procedure have been proven to safe and give a
patients could improves its symptoms. Metoclopramide good outcome result in improving gastroparesis, reduce
and domperidone also gives side effect such as gastric emptying period, and improve regurgitation
arrhythmia, and recommended to be stopped in patients symptoms in longer period.
with longer QT interval phenomenon. Antacid could be
used as breakthrough therapy, but should not be given
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also could be added as adjuvant therapy because this 1. Dent J, El-Serag H, Wallander M. Epidemiology of
JDVWURRHVRSKDJHDO UHÀX[ GLVHDVH D V\VWHPDWLF UHYLHZ *XW
aluminium chloride will give the protective effect to 2005;54:710–7.
LQÀDPHGPXFRVDO 2. (O6HUDJ+7LPHWUHQGVRIJDVWURHVRSKDJHDOUHÀX[GLVHDVHD
Surgical management as antireflux therapy systematic review. Clin Gastroenterol Hepatol 2007;5:17-26.
was emerging in the last decades. There were 3. Wong B, Kinoshita Y. Systematic review on epidemiology of
JDVWURHVRSKDJHDOUHÀX[GLVHDVHLQ$VLD&OLQ*DVWURHQWHURO
two procedures available commercially, transoral
Hepatol 2006;4:398-401.
incisionless fundoplication system (esophyx) and 4. Xia HH, Lai KC, Lam SK. Symptomatic response to
radiofrequency application. Esophyx used suction and ODQVRSUD]ROH SUHGLFWV DEQRUPDO DFLG UHÀX[ LQ HQGRVFRS\
transmural hooker to bind tissue in gastroesophageal negative patients with non-cardiac chest pain. Aliment
Pharmacol Ther 2003;17:369 –77.
junction to fundus and make a new valve/sphincter.24
5. Nakase H, Itani T, Mimura J. Relationship between asthma and
One prospective trail comparing laparoscopic JDVWURRHVRSKDJHDOUHÀX[VLJQL¿FDQFHRIHQGRVFRSLFJUDGH
antireflux surgery (LARS) and esomeprazole in RI UHÀX[ RHVRSKDJLWLV LQ DGXOW DVWKPDWLFV - *DVWURHQWHURO
refractory GERD. Five year remission was found in Hepatol 1999;14:715–22.
92% patients with esomeprazole, and 85% found in 6. Hampel H, Abraham NS, El-Serag H. Meta-analysis: obesity
and the risk for gastroesophageal reflux disease and its
/$56EXWQRVLJQL¿FDQWGLIIHUHQFHV%RWK/$56DQG complications. Ann Intern Med 2005;143:199–211.
HVRPHSUD]ROHSURYLGHDJRRG¿YH\HDUVUHPLVVLRQ26 7. Shapiro M, Green C, Bautista JM, Dekel R, Risner-Adler S,
Otherwise, Stretta procedure was a technique with :KLWDFUH 5$VVHVVPHQW RI GLHWDU\ QXWULHQWV WKDW LQÀXHQFH
endoluminal approach to give low radiofrequency SHUFHSWLRQRILQWUDRHVRSKDJHDODFLGUHÀX[HYHQWVLQSDWLHQWV
ZLWKJDVWURRHVRSKDJHDOUHÀX[GLVHDVH$OLPHQW3KDUPDFRO
energy in gastroesophageal junction. After Ther 2007;25:93–101.
radiofrequency application, it can be seen that LES 8. Iwakiri K, Kobayashi M, Kotoyori M, Yamada H, Sugiura T,
was thickening and it could reduce TLERS frequency, Nakagawa Y. Relationship between postprandial esophageal
UHÀX[HSLVRGHVDQGDOVRVHQVLWLYLW\WRDFLGH[SRVXUH acid exposure and meal volume and fat content. Dig Dis Sci
24 1996;41:926–30.
This procedure have been proven to safe and give a
9. El-Serag HB, Satia JA, Rabeneck L. Dietary intake and the
good outcome result in improving gastroparesis, reduce ULVN RI JDVWURRHVRSKDJHDO UHÀX[ GLVHDVH D FURVV VHFWLRQDO
gastric emptying period, and improve regurgitation study in volunteers. Gut 2005;54:11–17.
symptoms in longer period.27 10. Inadomi J, McIntyre L, Bernard L, Fendrick A. Step-
down from multiple-to single-dose proton pump inhibitors
(PPIs): a prospective study of patients with heartburn or
&21&/86,21 acid regurgitation completely relieved with PPIs. Am J
Gastroenterol 2003;98:1940-4.
*DVWURHVRSKDJHDO UHÀX[ GLVHDVH *(5' ZDV D 11. -RQHV 5+ +XQJLQ$3 3KLOOLSV - *DVWURHVRSKDJHDO UHÀX[
pathologic condition marked by mucosal damaged disease in primary care in Europe: clinical presentation and
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12. )DVV 5 (URVLYH HVRSKDJLWLV DQG QRQHURVLYH UHÀX[ GLVHDVH
ZDVEDVHGRQFOLQLFDO¿QGLQJVREMHFWLYHHQGRVFRSLF (NERD): comparison of epidemiologic, physiologic, and
examination, ambulatory reflux monitoring, and therapeutic characteristics. J Clin Gastroenterol 2007;
response to antiacid-secretion therapy. Symptoms of 41:131-7.
KHDUWEXUQDQGUHJXUJLWDWLRQZDVWKHVSHFL¿FV\PSWRPV 13. 0DNPXQ ' 3HQ\DNLW UHÀXNV JDVWURHVRIDJHDO ,Q 6XGR\R
A, Setiyohadi B, Alwi I, Simandibrata M, Setiati S, eds.
of GERD, and both could be the reason to start PPI Buku ajar ilmu penyakit dalam. 4th ed. Jakarta: Interna publ
WKHUDS\7KH¿UVWVWHSLQUHIUDFWRU\*(5'WUHDWPHQWLV 2009.p.480-9.
14. Giorgi F, Palmiero M, Esposito I, Cuomo R. Patophysiology 21. 5LWFKHU ( +RZ WR PDQDJH UHIUDFWRU\ *(5'" 1DW &OLQ
RIJDVWURHVRIDJHDOUHÀX[GLVHDVH$FWD2WRUKLQRODULQJRO,WDO Gastroenterol Hepatol 2007;4:658-64.
2006;26:241-6. 22. Kaltenbach T, Crockett S, Gerson LB. Are lifestyle measures
15. Altomare A, Guarinno M, Cocca S, Emerenziani S, Cicala M. HIIHFWLYHLQSDWLHQWVZLWKJDVWURHVRSKDJHDOUHÀX[GLVHDVH"$Q
*DVWURHVRSKDJHDOUHÀX[GLVHDVHXSGDWHRQLQÀDPPDWLRQDQG evidence-based approach. Arch Intern Med 2006;166:965–71.
symptom perception. World J Gastroenterol 2013;19:65230-8. 23. Hamilton JW, Boisen RJ, Yamamoto DT. Sleeping on a wedge
16. 0RUDHV)-5HIUDFWRU\JDVWURHVRSKDJHDOUHÀX[GLVHDVH$UT GLPLQLVKHVH[SRVXUHRIWKHHVRSKDJXVWRUHÀX[HGDFLG'LJ
Gastroenterol 2012;4:296-301. Dis Sci 1988;33:518–22.
17. Koek G, Sifrim D, Lerut T, Janssens J, Tack J. Effect of the 24. Hershcovici T, Fass R. Step by step management of refractory
GABA(B) agonist baclofen in patients with symptoms and JDVWURHVRSKDJHDOUHÀX[GLVHDVH'LV(VRSKDJXV
GXRGHQRJDVWURHVRSKDJHDOUHÀX[UHIUDFWRU\WRSURWRQSXPS 25. Fass R, Sontag S J, Traxler B, Sostek M. Treatment of
inhibitors. Gut 2003;52:1397-402. patients with persistent heartburn symptoms: a double-blind,
18. Moayeddi P, Talley N, Fenerti M. Can the clinical history randomized trial. Clin Gastroenterol Hepatol 2006;4:40–56.
GLVWLQJXLVKEHWZHHQRUJDQLFDQGIXQFWLRQDOG\VSHSVLD"-$0$ 26. Galmiche J, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund
2006;295:1566-76. S. Laparoscopic antireflux surgery vs esomeprazole for
19. Katz P, Gerson L, Vela M. Guidelines for diagnosis and chronic GERD: the LOTUS study. JAMA 2011;205:1969-77.
management of gastroesophageal reflux disease. Am J 27. Franciosa M, Triadafilopoulus G, Mashimo H. Stretta
Gastroenterol 2013;107:308-28. radiofrequency treatment: A safe and effective modality.
20. Dean B, Gano A, Knight K, Ofman J, Fass R. Effectiveness Gastroenterol Res Pract 2013;2013:1-8.
RISURWRQSXPSLQKLELWRUVLQQRQHURVLYHUHÀX[GLVHDVH&OLQ
Gastroenterol Hepatol 2004;2:656–64.