This document provides an overview of diagnostic testing for GERD, including 24-hour pH monitoring and multiple intraluminal impedance (MII) monitoring. It discusses the gold standard of 24-hour pH monitoring using probes placed 5 cm above the LES. The document also reviews advantages of the Bravo capsule for prolonged pH monitoring. Finally, it describes the combined MII-pH technique, which can classify reflux based on acidity as acid, weakly acidic, or weakly alkaline reflux using impedance to detect reflux and pH to measure acidity.

1. Gold standard for the diagnosis of GERD
Samir Haffar M.D.
Assistant Professor of Gastroenterology
Al-Mouassat University Hospital – Damascus – Syria

2. The reflux pyramid

3. Diagnosis of GERD
• History
• PPI trial
• UGI endoscopy (LA classification)
• 24 hour pH monitoring
• Bravo capsule
• Combined MII & pH monitoring (MII- pH)
• Bilitec (alkaline reflux)

4. 24 hours pH monitoring

5. Ideal pH electrode
“No single probe meets all of these criteria”
• Small
• Firm enough
• Rapid response time between pH 7 to pH 1
• Minimally affected by temperature
• No hysteresis effect
• No drift during 24 hours
• Inexpensive
• Simple to calibrate or disposable

6. Location of the LES
• Manometric localization
• pH step-up method Sudden rise to pH > 4
• LES locator Prior to pH
• Fluoroscopic techniques Not accurate
• Endoscopic technique Not accurate
Reference method

7. Sites of 24 hour pH monitoring
• Single monitoring site: 5 cm above LES
• Multiple monitoring sites: 5 & 20 cm above LES
• One in esophagus & one in proximal stomach (NAB*)
• One or more in esophagus & another in hyopharynx
* NAB: Nocturnal Acid Breakthrough

9. Typical monitoring sites of 5 & 20 cm
above manometrically determined LES

10. Why 5 cm above LES ?
• Has been standard for many years
• Chosen to avoid catheter migration into the stomach
• Moving by a 1 cm or two would not change results
• Moving it 10 cm above LES miss a number of patients
who are identified by the more distal location

11. Why pH < 4?
• Defined early in development of the technology
• Its choice based on:
- Marked difference from normal esophageal pH of 7
- Pepsinogen converted to pepsin at pH 4
- pH < 4 tends to produce symptoms
• Some believe that drops in pH that do not reach level
of 4.0 still may represent reflux

12. Composite scoring systems
Johnson & DeMeester is the most commonly used
Percentage of total time pH < 4
Percentage of upright time pH < 4
Percentage of supine time pH < 4
Number of reflux episodes
Number of reflux episodes >5 min
Longest reflux episode
DeMeester score
Normal 14,72

13. Normal values of DeMeester’s score
50 healthy volunteers
DeMeester TR et al. Ann Surg 1976 ; 184 :459 – 470.

14. Postprandial acid exposure
Postprandial acid exposure in the esophagus
Some upright reflux
Major contribution from postprandial period
DeMeester score: 29.3 – Normal < 14.72 (95th percentile)

15. Proximal & distal esophageal pH monitoring

16. Nocturnal acid breakthrough
Intragastric pH < 4 for > 1 h overnight during PPI

17. Nocturnal acid breakthrough
• Defined arbitrarily as intragastric pH < 4 for > 1 h
overnight during PPI administration
• Occurs even on twice-daily PPI therapy
• Common enough: rule rather than exception
• Not without controversy: little to do with reflux
• H2RAs at bedtime + PPI bid better than PPI alone?

18. Symptom association
• Symptom index ≥ 50%
• Symptom sensitivity index: > 10 %
• Symptom association probability calculation: 95%
• Integrated acidity
Simply giving impression of potential association

19. Symptom index
Positive if ≥ 50 %
Not take into account overall number of reflux episodes

20. Symptom sensitivity index
Positive if 10 %
Not take into account overall number of symptoms

21. Symptom association probability calculation
Positive if 95%
• Divides tracing into 2-min segments & looks at whether
a symptom & acid present during each 2 min segment
• Analysis uses contingency table analysis of 4 possible
outcomes for each segment:
acid + symptom +
acid + symptom –
acid – symptom +
acid – symptom –

22. Integrated acidity
• Integrating the pH & converting it to H+ concentration
for each second of an ambulatory tracing
• This index continues to be studied
Has not been shown to be clinically useful

23. Overall amount of acid exposure & number of
reflux episodes are the focus of many studies
using ambulatory pH testing
Relationship between symptoms & esophageal
acid is equally (or perhaps more) important

24. 24 hour pH esophageal monitoring
Off & on therapy
• Off therapy
Uncertainty about diagnosis of reflux
Mildest grades of esophagitis: redness - friability
Very short segments of BE
• On therapy
Patient who has failed a therapeutic trial
pH probe in esophagus & another in stomach (NAB)

25. 24 hours pH monitoring
off therapy
• PPI should be stopped for 5 – 7 days
• H2RA should be stopped 48 hours before the study
• Patient must not use antacids or other OTC
medications for duration of the study

26. Percentage of total time pH < 4
Normal values
• Off therapy
5 cm above LES 4 – 5.5 %
20 cm above LES 1 %
Periods of meals or acidic beverages excluded
• On therapy
5 cm above LES 1.6 – 4 %
20 cm above LES ?

27. Indications of esophageal pH recording*
• Normal endoscopic findings & reflux symptoms refractory to PPI
• Endoscopy-negative patient before surgical anti-reflux repair
• Patients suspected to have abnormal reflux after surgery
• Refractory reflux in pts with chest pain after cardiac evaluation
• Suspected ENT manifestations after failure of 4 weeks of PPI
• GERD in an adult onset nonallergic asthma
*AGA Medical Position Statement. Gastroenterology 1996 ; 110 : 1981 – 1996.

28. No indications of esophageal pH recording*
• Not indicated to detect or verify reflux esophagitis
(this is an endoscopic dg)
• Not indicated to evaluate „„alkaline reflux‟‟
*AGA Medical Position Statement. Gastroenterology 1996 ; 110 : 1981 – 1996.

29. Abnormal acid exposure time in heartburn
Disease Percentage of total time pH < 4
Barrett‟s esophagus 93 %
Erosive esophagitis 75 % (in one study)
ENRD*
NERD*
Functional heartburn
- SI > 50%
- SI < 50%
50 %
100 %
0 %
Hypersensitive esophagus
Non acid reflux or motor event
* ENRD Endoscpic Negative Reflux Disease
* NERD Non Erosive Reflux Disease

30. Limitations of esophageal pH monitoring
Is it the gold standard?
• Normal 24 hr pH in 25% of patients with erosive esophagitis
• Some patients with very convincing histories but negative
endoscopy & normal pH test
• Differences in acid exposure documented between 2 pH
probes attached to each other & used simultaneously
• Day-to-day variability may be seen with normal pH study
in one day & abnormal in another day

31. Bravo capsule
(Medtronic)

32. Bravo system (Medtronics)
Esophageal Probe
25 x 6 x 5.5 mm
Battery
pH
electrode
Suction
chamber
Radio
transmitter
Delivery system
Receiver
100 x 70 x 30 mm - 165 g

33. Advantages of Bravo capsule
• Better tolerance by patients
• Fixed position of the capsule
• Prolonged monitoring under more physiologic
conditions (48 hours)

34. Bravo normal values
50 asymptomatic volunteers

35. Conventional pH vs Bravo capsule
Head to head comparison – 40 patients
Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
CPHMS Conventional pH Measurement System
CFS Catheter Free System

36. Bravo capsule
Causes of under-recording
• Data drop-up
• Short reflux event not recorded
• Reflux events appear shorter

37. Bravo capsule
Data drop-out
Malfunctions in the electronics or the receiver
Interpreted as artifact & not represented in final pH report
Improved by 7 cm antenna & use of fiberglass
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318.

38. Bravo capsule
Short reflux events not recorded
Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
CPHMS Conventional pH Measurement System
CFS Catheter Free System

39. Bravo capsule
Reflux events appear shorter
Bruley des Varannes S. Gut 2005 ; 54 ; 1682 – 1686.
CPHMS Conventional pH Measurement System
CFS Catheter Free System

40. Trouble shooting in Bravo capsule
• Severe odynophagia & chest pain (5%)
Chest radiography to exclude perforation
Viscous lidocaine
Endoscopic removal if symptoms continue
• Capsule dislodgment
• Failure to disloge
Endoscopic removal similar to polypectomy

41. Bravo capsule
Classic early dislodgement
Easily recognized during inspection of pH tracing
Sudden prolonged drop in pH represents capsule in stomach
Sharp rise as capsule enters small intestine through pylorus
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318.

42. Endoscopic removal of Bravo capsule
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 307 – 318.

43. Normal values of Bravo capsule
Pandolfino 1 Portale 2
No of healthy subjects 44 38
% total time pH < 4 2.3 %
95th percentile 5.9 % 5.9 %
1- Pandolfino JE et al. Am J Gastroenterol 2003 ; 98 : 740 - 9.
2- Portale G et al. Gastroenterology 2003 ; 124 : A536.
Further validation are required

44. Multiple Intraluminal Impedance
(MII)

45. Multiple Intraluminal Impedance (MII)
• Relatively new technique developed in early 1990s
at Helmholtz Institute in Aachen (Germany)
• Silny* provided first description of this technique that
assesses intraluminal bolus movement by measuring
changes in conductivity of intraluminal content
* Silny J. J Gastrointest Motil 1991 ; 3 : 151 – 62.

46. Principle of “MII”
• 2 steel rings separated by isolator
• Alternating-current generator to apply electrical PD
• Circuit can only be closed through electrical charges (ions)
contained in structures surrounding the catheter
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.

47. Impedance scale
Refluxate High conductivity & low impedance
Air Low conductivity & high impedance
Bremner CG et al. Esophageal disease & testing.
Taylor & Francis Group, New York, 1st edition, 2005.

48. Advantages of MII
• Content of refluxate Liquid - Gas - Mixed
• Direction of bolus Anterograde - retrograde
• Height of refluxate
• pH characteristics Acid
(combined MII-pH) Weekly acid
Weekly alkaline
Superimposed reflux (re-reflux)

49. Liquid bolus
1) Initial drop Liquid enters impedance-measuring segment
2) Rise Bolus cleared from this segment
3) Overshoot Decreased luminal cross-section during contraction
4) Return to baseline
Atlas of investigation & management of esophageal diseases
Clinical publishing , Oxford, UK, 2006.

50. Representation of MII & motility recording
Impedance waveform opposite to contraction waveform
Bolus exit point occurs in front of contraction wave
Bremner CG et al. Esophageal disease & testing.
Taylor & Francis Group, NY, 1st edition, 2005.

51. Air bolus
(Belch, Air swallow)
1) Rapid rise Presence of air bolus inside esophagus
2) Rapid decrease Air bolus clears from this segment
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 - 264.

52. Mixed air – liquid Bolus
1) Rapid Rise Air in front of the bolus
2) Rapid drop Liquid component of mixed bolus
3) Rise Liquid being cleared from this segment
4) Return to baseline
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.

53. Mixed liquid – air bolus
1) Rapid drop Liquid enters impedance measuring segment
2) Rapid rise Gas reaches the segment
3) Rapid fall Gas exits the segment
4) Return to baseline
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 257 – 264.

54. Antegrade bolus movement (MII)
Observed during swallowing
Progression of impedance from proximal to distal
Atlas of investigation & management of esophageal diseases
Clinical publishing , Oxford, UK, 2006.

55. Retrograde bolus movement (MII)
Observed in reflux
Progression of impedance from distal to proximal
Atlas of investigation & management of esophageal diseases
Clinical publishing , Oxford, UK, 2006.

56. Combined MII
• MII used clinically only in combination
– With esophageal manometry (MII-EM)
– With pH (MII-pH)
• MII not considered as replacement for manometry &
pH techniques but as complementary procedure that
expands diagnostic potential of esophageal function
testing & reflux monitoring

57. Combined MII-pH probe
• Impedance orifices
3, 5, 7, 9, 15, & 17 cm
from the catheter tip
• pH orifice
5 cm from the catheter tip
• MII-pH probe = pH probe
Do not change patient comfort
Bremner CG et al. Esophageal disease & testing.
Taylor & Francis Group, NY, 1st edition, 2005.

58. “Sleuth” monitor – Sandhill
“Sleuth” monitor attached to the catheter
& worn around a belt during the recording period

59. GERD classification by combined MII-pH
• Acid reflux
Reflux with drop of pH from above 4.0 to below 4.0
• Superimposed acid reflux (Acid re-reflux)
Acid reflux occurs while pH < 4.0
• Weakly acidic reflux
Reflux results in esophageal pH between 4.0 & 7.0
• Weakly alkaline reflux
Reflux with nadir esophageal pH does not drop < 7.0
Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.

60. Acid reflux (MII-pH)
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.

61. GERD classification by combined MII-pH
• Acid reflux
Reflux with drop of pH from above 4.0 to below 4.0
• Superimposed acid reflux (Acid re-reflux)
Acid reflux occurs while pH < 4.0
• Weakly acidic reflux
Reflux results in esophageal pH between 4.0 & 7.0
• Weakly alkaline reflux
Reflux with nadir esophageal pH does not drop < 7.0
Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.

62. Superimposed acid reflux (MII-pH)
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.

63. GERD classification by combined MII-pH
• Acid reflux
Reflux with drop of pH from above 4.0 to below 4.0
• Superimposed acid reflux (Acid re-reflux)
Acid reflux occurs while pH < 4.0
• Weakly acidic reflux
Reflux results in esophageal pH between 4.0 & 7.0
• Weakly alkaline reflux
Reflux with nadir esophageal pH does not drop < 7.0
Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.

64. Weakly acidic reflux (MII-pH)
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.

65. GERD classification by combined MII-pH
• Acid reflux
Reflux with drop of pH from above 4.0 to below 4.0
• Superimposed acid reflux (Acid re-reflux)
Acid reflux occurs while pH < 4.0
• Weakly acidic reflux
Reflux results in esophageal pH between 4.0 & 7.0
• Weakly alkaline reflux
Reflux with nadir esophageal pH does not drop < 7.0
Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.

66. Weakly alkaline reflux (MII-pH)
Gastrointest Endoscopy Clin N Am 2005 ; 15 : 361 – 371.

67. Esophageal bilirubin monitoring
(Bilitec - Medtronic)

68. Importance of DGER
Best Pract Res Clin Gastroenterol 2000 ; 14 : 719 – 729.

69. Bilitec recorder

70. Principles of Bilitec
• Utilizes optical properties of bilirubin
Spectrophotometric absorption band at 450 nm
• Detection in esophageal lumen of absorption near 450
nm suggests presence of bilirubin & therefore DGER
• DGER is defined when bilirubin absorbance > 0.14
DGER is terminated when bilirubin absorbance < 0.14
Value < 0.14 due to particle & mucus in gastric content

71. Correlation between absorbance & bilirubin
concentration

72. Limitations of Bilitec
• Semi-quantitative means of detecting DGER
Cannot detect onset or frequency of DGER
• Underestimate bile reflux by 30% if pH < 3.5
Must be accompanied by 24 h esophageal pH
• Require use of liquid diet to avoid false positivity
• Few medical conditions (Gilbert & Dubin Johnson)
may result in disproportionate secretion of bilirubin
compared to other contents of bile

73. Foods that can be eaten for the Bilitec study
• Bananas
• Apples
• Saltine crackers
• Cottage cheese
• Chicken breast (baked, broiled, boiled, no skin)
• Rice
• Cream of chicken or cream of mushroom soup

74. Esophageal pH & Bilitec study
Maximal bile reflux in the esophagus during supine period
Bremner CG et al. Esophageal disease & testing. Taylor & Francis Group, 2005.

75. Combined MII-pH & Bilitec
Weakly alkaline reflux may or may not include
duodenal contents
Sifrim D et al. Gut 2004 ; 53 ; 1024 – 1031.

76. Despite its limitations, Bilitec is an important
advance in assessment of DGER in clinical arena

77. Advantages of 3 major types of pH testing
pH Bravo
Capsule
Combined
MII-pH
Comfort _ + _
Monitoring > 24 h _ + _
Nonacid reflux _ _ +
Normal values + _ _
Proximal reflux + ? +
Gastric monitoring + ? +

78. Conclusion
• 24 hour pH esophageal monitoring is not the gold
standard for diagnosis of GERD
• Combined MII-pH of the esophagus is the best
available diagnostic test for diagnosis of GERD at
the present time

79. Thank You