Impedance Koya-2008

Impedance detected abnormal bolus transit in patients with normal esophageal manometry.Sensitive indicator of esophageal functional abnormality?

D.L.Koya,1A.Agrawal,2J.

E.Freeman,2D.O.Castell2

1Division of General Internal Medicine,2Division of Gastroenterology and Hepatology,Medical University of South Carolina,Charleston,South Caroline,USA

SUMMARY.When used in combination with manometry,multichannel intraluminal impedance better charac-terizes the established manometric abnormalities into those with and without associated transit defects.However, the signi?cance of the?nding of normal manometry and abnormal impedance is not known.The objective of this study is to evaluate the clinical relevance of abnormal impedance associated with normal manometry during esophageal function testing in patients with a variety of esophageal symptoms.All patients referred for esophageal function testing during a27-month period underwent combined multichannel intraluminal impedance and esoph-ageal manometry studies including10liquid and10viscous swallows in supine position.From576patients with normal esophageal body manometry we identi?ed158patients(27%)with abnormal impedance.The primary symptom in these158patients was compared to that in146consecutive patients with normal manometry and normal impedance selected from the original576patients.Abnormal bolus transit was found with viscous,liquid and both type swallows in60%,19%and21%of the patients respectively.Of patients with abnormal bolus transit, 23%presented with dysphagia compared to10%of normal transit patients(p=0.0035).In conclusion,abnormal impedance even in patients with normal manometry may be a sensitive indicator of esophageal functional abnor-mality as represented by the symptom of dysphagia in these patients.Abnormal transit was more frequently identi?ed with viscous than liquid swallows.Prospective studies to further clarify impedance detected transit defects in patients with normal manometry and the role of viscous swallows in diagnostic testing are warranted.

KEY WORDS:abnormal impedance with normal manometry,dysphagia,MII–EM.

INTRODUCTION

Esophageal motility abnormalities are typically evalu-ated using esophageal manometry(EM).1,2EM only provides information about intraluminal pressures, necessitating techniques like video?uoroscopy or radionuclide scintigraphy for the evaluation of bolus transit during swallowing.3,4However,these imaging techniques are associated with radiation exposure and are usually not performed simultaneously with manometry,limiting their application for assessment of bolus transport in clinical practice.Multichannel intraluminal impedance(MII)monitoring is a new non-radiation technique for assessment of bolus transit during swallowing.5–7Esophageal impedance testing has shown to have good correlation with video ?uoroscopy and manometry.6–12When used in combi-nation with manometry,impedance helps to better characterize the established manometric abnormali-ties as those associated with either abnormal or normal bolus transit.13In a group of350patients referred for esophageal function testing(EFT)with various esophageal symptoms,Tutuian and Castell found that combined multichannel intraluminal impedance and esophageal manometry(MII–EM) provided important functional details of esophageal motility abnormalities.They found normal bolus

Address correspondence to:Dr Deepika L.Koya,MD,MSCR,

Division of General Internal Medicine,Medical University of

South Carolina,135Rutledge Ave,Room280,Charleston,SC

29425,USA.Email:koyald@https://www.360docs.net/doc/c29836722.html,

Authors’contributions:D.L.Koya collected the data,conceived

of the study,designed and conducted the analysis,and led the

writing.A.Agrawal assisted in data collection and conceived of

the study.J.E.Freeman assisted in data collection and

preparation of the manuscript.D.O.Castell conceived of the

study,and supervised the study design,and preparation of the

manuscript.All authors helped to conceptualize ideas,interpret

?ndings,and revise the manuscript.

?2008Copyright the Authors

Journal compilation?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus1

transit for liquid in almost all patients with normal EM,nutcracker esophagus and poorly relaxing, hypertensive,or hypotensive lower esophageal sphincter(LES).In their evaluation of the relationship between transit abnormalities and patient’s presenting symptom,they found that the symptom of dysphagia was signi?cantly more prevalent in patients with abnormal liquid and/or viscous bolus transit.14In their study evaluating40patients with non-obstructive dysphagia using MII–EM,Conchillo et al.found that35%(6/17)of dysphagia patients with normal manometry had abnormal liquid and/or viscous transit.15Their?ndings suggest that in patients with dysphagia,addition of impedance to EFT testing identi?ed a transit defect even in those with normal manometry.

With increasing application of combined MII–EM in the evaluation of esophageal functional defects,we found that abnormal bolus transit with liquid and/or viscous swallows is found in some patients with normal manometry.The relevance of?nding abnor-mal bolus transit and normal manometry as detected by combined MII–EM in the evaluation of patients with a variety of esophageal symptoms is not well-known.

In this study,we sought to document the fre-quency of and evaluate the clinical relevance of ?nding abnormal transit in patients with normal manometry referred for esophageal function testing using MII–EM.

METHODS

Since July2002,all patients referred to our labora-tory have undergone EFT by combined MII–EM technique.Institutional Review Board of Medical University of South Carolina(Charleston,SC) approved publishing information from EFT testing. The primary symptom for which patients were referred for testing was recorded from the physician’s referral correspondence.When this information was not available,it was obtained from a questionnaire completed by the patients prior to the testing,which includes detailed questions about their chief com-plaint.In our tertiary center,patients are referred from the community typically after the initial workup for dysphagia(i.e.barium esophagram and upper gastrointestinal(GI)endoscopy)was performed. Details of many of these studies were not available. Details of the EFT testing

Each patient underwent EFT by combined MII–EM using a Koenigsberg9-channel probe(Sandhill EFT catheter;Sandhill Scienti?c,Inc.,Highlands Ranch, CO,USA).The catheter was4.5mm in diameter with two circumferential solid-state pressure sensors at5and10cm and three unidirectional solid-state pres-

sure sensors at15,20,and25cm from the tip of the

catheter.Impedance measuring segments consisting

of metal rings placed2cm apart,were centered10,

15,20,and25cm from the tip of the catheter,

straddling the four proximal pressure transducers.

The EFT catheter was inserted intranasally into the

esophagus up to a depth of60cm.The LES was

identi?ed by using a stationary pull-through tech-

nique,and the most distal sensor was placed in the

high-pressure zone of the LES.Intra-esophageal

pressure sensors and impedance measuring segments

were thus located at5,10,15,and20cm above the

LES.Patients received10swallows of5cc normal

saline(liquid swallows)and10swallows of5cc

viscous material(viscous swallows)each20–30

seconds apart in the supine position.

Manometric parameters that characterize swallows Manometric parameters used to characterize esoph-

ageal body manometry included:(i)contraction

amplitudes at5and10cm above the LES;(ii)distal

esophageal amplitude(DEA)as average of contrac-

tion amplitudes at5and10cm above the LES;and

(iii)onset velocity of esophageal contractions in the

distal part of the esophagus.Based on these mano-

metric parameters,swallows were classi?ed as either

normal,ineffective,or simultaneous.

?Normal swallows–contraction amplitudes at5

and10cm above the LES?30mmHg and onset

velocity<8cm/second

?Ineffective–if either of the contraction amplitudes

at5and10cm above the LES<30mmHg

?Simultaneous–contraction amplitudes at5and

10cm above the LES?30mmHg and distal veloc-

ity>8cm/second

Overall diagnosis of normal manometry

Using10saline swallows,the diagnosis of normal

EM was made based on the revised criteria suggested

by Tutuian and Castell.16Prior to the introduction of

MII–EM testing,the diagnoses of ineffective esoph-

ageal motility(IEM)(?30%saline swallows with

contraction amplitude<30mmHg in either one of the

two distal sites located5and10cm above the LES)

and normal EM(not more than20%ineffective and

not more than10%simultaneous swallows with DEA <180mm Hg and with normal LES resting and residual pressures)were made based on EM alone

with no direct assessment of esophageal bolus clear-

ance.17In their study evaluating the esophageal

function in70patients with IEM using the MII–EM

technique,Tutuian and Castell found that patients

with?5manometric ineffective liquid swallows were

signi?cantly more likely to have abnormal bolus

transit than patients with the current manometric

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?2008Copyright the Authors Journal compilation?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus

de?nition of IEM (?3liquid ineffective swallows).16Based on these ?ndings,the authors suggested a revi-sion of existing criteria for de?ning IEM and normal manometry.We de?ned normal EM as not more than 50%ineffective and not more than 10%simultaneous swallows with DEA <180mmHg.

All the patients in our study had normal esoph-ageal peristalsis.In their study evaluating functional aspects of various motility abnormalities using MII–EM,Tututian and Castell found that isolated LES abnormalities in those with normal esophageal body pressures do not signi?cantly affect bolus transit.14For this reason,the ?nal diagnosis of normal manometry in our study was based on esophageal body manometry alone.

MII parameters that characterize swallows

Bolus entry at each speci?c level was considered at the 50%point between the 3-second pre-swallow impedance baseline and impedance nadir during bolus presence.Bolus exit was determined as return to this 50%point on the impedance recovery curve.The bolus was considered to exit a given level in the esophagus if the impedance recovered to greater

than the 50%baseline value for at least 5seconds.The bolus was considered not to exit the segment if it did not recover to either greater than the 50%base-line value or recovered for <5seconds.Based on these MII parameters,swallows were classi?ed as follows:(i)complete bolus transit if bolus entry occurred at the most proximal site (20cm above the LES),and bolus exit points were recorded in all three distal impedance-measuring sites (i.e.15cm,10cm,and 5cm above the LES);and (ii)incomplete bolus transit if bolus exit was not identi?ed at any one of the three distal impedance measuring sites (Fig.1).Overall diagnosis of esophageal transit abnormalities Transit abnormalities were de?ned as abnormal liquid transit if 30%or more of the 10liquid swallows had incomplete transit and abnormal viscous transit if 40%or more of 10viscous swallows had incomplete bolus transit.These transit abnormalities were de?ned based on prior established criteria derived from a study in 43healthy volunteers.10It has been suggested that abnormal transit for both liquid and viscous swallows be considered severe esophageal functional abnormality whereas abnormalities

in

Fig.1Examples of studies showing normal manometry with normal transit and normal manometry with abnormal transit (a)liquid swallow showing normal manometry with abnormal transit (2nd impedance site),(b)viscous swallow showing normal manometry with abnormal transit (3rd impedance site),(c)liquid swallow showing normal manometry with normal transit.Abnormal impedance with normal manometry 3

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Journal compilation ?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus

transit for either liquid or viscous swallows is a mod-erate functional defect.This categorization of sever-ity of transit defects is in accordance with those made in previous studies in patients with IEM.15,17Statistical analysis

Descriptive statistics were used to describe impedance characteristics in patients with normal manometry and abnormal transit.Differences in symptom of pre-sentation between patients with normal manometry and abnormal transit and those with normal manom-etry and normal transit were assessed by chi-square tests.We considered a 2-tailed P value of <0.05sta-tistically signi?cant for all analyses.SAS v 9.1(Cary,NC,USA)was used for all statistical analyses.

RESULTS

Between July 1,2002,and October 31,2004,we iden-ti?ed 589combined MII–EM studies with normal manometry.While all these patients received 10liquid and 10viscous swallows,13patients with normal manometry with liquid swallows could not complete the test with viscous swallows and were excluded.Of the 576patients with normal manom-etry,who completed testing with both liquid and viscous swallows,158patients (27.4%)had abnormal transit for liquid or viscous swallows,or both.EFT was performed as either a primary diagnostic proce-

dure for evaluation of esophageal symptoms or prior to ambulatory pH monitoring.Of the 158patients,95(60%)had abnormal transit for viscous only and 30(19%)for liquid swallows only.These were consid-ered to have a moderate transit defect.Severe transit defect de?ned as abnormal transit for both liquid and viscous swallows was found in 33patients (21%,Fig.2).Thus,128of these 158patients (81%)had impaired viscous transit and 63(40%)had abnormal liquid transit.

Primary symptom and impedance characteristics:Normal manometry and abnormal transit

The primary symptom for which the 158patients were referred for EFT testing was heartburn/regurgitation (25%),dysphagia (23%),abdominal pain/nausea (14%),cough (9%),hoarseness/throat clearing (8%),and globus (5%,Table 1).The propor-tion of patients presenting with the symptom of dys-phagia among those with transit defects for viscous only,liquid only,and both liquid and viscous was 23,27,and 18%,respectively (Fig.3).

Although all these patients had normal manom-etry which was de?ned only based on liquid swallows,about 19%had abnormal manometry for viscous swallows,as recently de?ned by Blonski et al .According to their study,the normal manometric values for viscous swallows were ?60%ineffective contractions (<30mmHg),?10%simultaneous contractions,and distal esophageal amplitude <204mmHg.18Of the 30/158(19%)with

abnormal

102030405060

70Abnormal V only Abnormal both V+L Abnormal L only

Type of abnormal transit

% o f p a t i e n t s

Fig.2Proportion of patients with normal manometry and abnormal transit,according to the type of transit abnormality (V =viscous;L =liquid).

Table 1Comparison of primary symptom:abnormal transit versus normal transit

Symptom

Normal manometry with abnormal transit n =158(%)Normal manometry with normal transit n =146(%)P -value Dysphagia

36(22.8)15(10.3)0.0035Heartburn/regurgitation 39(24.7)52(35.6)0.04Abdominal pain/nausea 22(13.9)13(8.9)NS Cough 14(8.9)13(8.9)NS Chest pain 27(17.1)30(20.6)NS Hoarseness 12(7.6)13(8.9)NS Globus

8(5.1)

10(6.9)

NS

NS,

non-signi?cant.

51015202530Viscous Liquid Liquid & Viscous

Type of abnormal transit

% o f p a t i e n t s w i t h D y s p h a g i a

Fig.3Percentage of patients with dysphagia,according to bolus transit abnormality among patients with abnormal transit and normal manometry.

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?2008Copyright the Authors

Journal compilation ?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus

viscous manometry,21/158(13%)had more than60% ineffective viscous swallows and9/158(6%)had more than10%simultaneous viscous swallows. Comparison of demographics and primary symptom: normal transit versus abnormal transit

In patients with normal manometry,demographic characteristics and primary symptom were compared between patients with normal transit and those with abnormal transit.Of the original576patients with normal manometry,146consecutive patients with normal esophageal body manometry,normal transit and normal LES resting and residual pressures with complete information on demographics,and symptom information were included in the normal transit group.We found no signi?cant differences in age,gender,and race between the146patients with

normal transit versus the158with abnormal transit (Table2).The frequency of dysphagia was signi?-cantly(P=0.0035)greater(36/158,23%)in patients with abnormal bolus transit compared with those with normal transit(15/146,10%).In contrast,the frequency of typical re?ux symptoms(heartburn or regurgitation39/158,25%)was signi?cantly lower (P=0.04)in patients with abnormal transit com-pared with normal transit patients(52/146,36%; Fig.4).There were no signi?cant differences between the two groups in the frequency of presentation of other symptoms(Table1).There are3/36(8%) patients with dysphagia in the abnormal transit group who had fundoplication whereas none in the normal transit group had post fundoplication dysph-agia.No signi?cant difference in the mean LES residual pressure was found between the normal transit and abnormal transit groups(P=0.1350). Similarly,the mean LES resting pressure was not signi?cantly different between the two groups (P=0.089).

DISCUSSION

Our study?ndings suggest that,even with normal esophageal contractility,the MII component of MII–EM testing was sensitive in detecting esophageal transit abnormalities that contributed to the symptom of dysphagia.Without MII,these patients with impaired clearance would have been described as normal.Among the patients with abnormal transit,differences in transit patterns for liquid and viscous swallows were found.The majority had impaired viscous bolus transit(81%).

In their study evaluating the esophageal functional details of350patients with a variety of esophageal symptoms,Tutuian and Castell found a signi?cant association between the symptom of dysphagia and abnormal bolus transit when using MII–EM.14The transit defects in these patients were associated with manometrically de?ned motility abnormalities includ-ing achalasia,scleroderma,IEM,or distal esophageal spasm(DES).Our study also found an association between frequency of dysphagia and bolus transit defect even with no detectable manometric abnormal-ity.Studies exploring the utility of MII–EM in evalu-ation of patients with esophageal symptoms suggest that adding impedance to manometry better charac-terizes the existing manometric abnormalities into those associated with transit defects and those with only pressure defects.13We found that the impedance technique not only complements manometric abnor-malities but is also sensitive in detecting transit defects independent of pressure abnormalities.Our data suggest that we should consider adding an additional motility abnormality called‘normal manometry with abnormal transit’to the classi?cation of esophageal motility abnormalities.

The clinical relevance of?nding normal manom-etry with abnormal transit in MII–EM studies has been described in patients with non-obstructive dys-phagia(NOD)and post-fundoplication dysphagia. In their study evaluating the value of adding MII to EM in40patients with NOD,Conchillo et al.found that6/17(35%)of NOD patients with normal manometry had abnormal liquid and/or viscous tran-

Table2Demographic characteristics:abnormal transit versus normal transit

Demographics Normal manometry

and abnormal

transit(n=158)

Normal manometry

and normal

transit(n=146)

Age in years(mean)5656 Gender

Female104(66%)104(71%) Male54(34%)42(29%) Race

White129(82%)121(83%) Black27(17%)23(16%) Asian/Hispanic2(1%)2

(1%)

5

10

15

20

25

30

35

40

Dysphagia Heartburn/Regurgitation

%

o

f

p

a

t

i

e

n

t

s

Fig.4Percentage of patients presenting with dysphagia and gastroesophageal re?ux disease(GERD)having normal transit with normal manometry versus abnormal transit with normal manometry.Normal transit with dysphagia n=15,abnormal transit with dysphagia n=36,P=0.0035;normal transit with GERD symptoms n=52,abnormal transit with GERD symptoms n=39,P=0.037.

Abnormal impedance with normal manometry5

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Journal compilation?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus

sit.15In another study,which evaluated patients with post-fundoplication dysphagia using MII–EM,Yigit et al.found that esophageal transit was impaired in the majority of patients,even with normal fundopli-cation anatomy and normal peristalsis on manom-etry.19In both studies,some abnormalities in esophageal motility were only detected by MII and would have been interpreted as normal if only the manometry technique had been used.Consistent with these studies,we found a signi?cant association between dysphagia and impaired bolus transit in the presence of normal motility compared with patients with normal transit in patients evaluated for a variety of esophageal symptoms.However,a signi?cant association with symptoms(heartburn/regurgitation) usually considered typical symptoms of gastroesoph-ageal re?ux disease(GERD),was found in a normal transit group of patients.It is not entirely clear why typical GERD symptoms are more prevalent in the normal transit group.However,many of these patients had MII–EM testing done to establish the location of LES as a pretest for ambulatory pH moni-toring for typical GERD symptoms.It appears that a common manometric?nding in these patients with typical GERD symptoms is normal MII–EM.

In the original study by Tutuian and Castell evalu-ating transit abnormalities in350patients using MII–EM,only5%of patients with normal manometry had abnormal bolus transit for liquid swallows.14The increase in prevalence of abnormal transit with normal manometry seen in our study has two possible explanations.First,the higher prevalence of abnor-mal transit with normal manometry is,in part,due to the viscous swallows,which may be more sensitive than saline swallows to detect transit abnormalities in the presence of normal manometry.In19%of patients,these transit abnormalities are associated with abnormal viscous manometry(either an IEM or DES pattern in viscous swallows only).If viscous manometry is considered in de?ning normal manom-etry,these patients would be categorized as IEM or DES.Consistent with our?nding,Blonski et al. found that viscous solution is more sensitive in detecting various manometric abnormalities.20 Another possible explanation for the high rate of abnormal transit we found relates to the change in criteria for IEM from three ineffective swallows to ?ve ineffective swallows,which would have moved 46/158(29%)patients from the category of IEM to normal manometry with abnormal transit.We did not?nd a signi?cant association between the propor-tion of patients with dysphagia and the severity of transit defect(i.e.moderate or severe),suggesting that this proposed categorization may not be as useful as previously suggested.

There are several limitations to our study.First,as this is a cross-sectional study,we can only conclude that abnormal transit is signi?cantly associated with dysphagia and no inferences about causality of dys-phagia can be made.Second,because some of the patients included in our study were referred to us from the community after their initial workup for dysphagia(i.e.barium esophagram and upper GI endoscopy),we were unable to con?rm that their barium esophagrams and endoscopies were normal. However,their referral for EFT testing suggests the presence of non-obstructive dysphagia.

Simultaneous impedance testing is known to complement EM by clarifying functional details of bolus transit in patients with esophageal motility abnormalities.Also,it is a sensitive test in detecting transit abnormalities independent of esophageal contractility as represented by the symptom of dys-phagia.Outcome-based prospective studies are needed to clarify the role of impedance testing in patients with esophageal symptoms.Prospective studies are also warranted to de?ne further the role of viscous swallows in clarifying the functional details of motility abnormalities.

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Abnormal impedance with normal manometry7

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Journal compilation?2008,Wiley Periodicals,Inc.and the International Society for Diseases of the Esophagus