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Proximal Aero-Digestive and Respiratory Interactions in Infants With HypoxicIschemic Encephalopathy (HIE)Ish K. Gulati, Theresa Shubert, Xiaoyu Gao, Sudarshan Jadcherla

BACKGROUND: Management of oral secretions and aerodigestive symptoms is a challengingproblem in infants with HIE. Timeliness and coordination of neuromotor activation inresponse to pharyngeal stimulation are crucial for swallowing and airway protection. Wehave demonstrated that neonates with HIE have altered esophageal body response kineticswhen compared with healthy controls, but mechanisms regarding the pharyngeal phase ofdysphagia remain unclear. AIMS: To test the hypothesis that in infants with HIE, pharyngealprovocation alters swallowing and upper esophageal sphincter (UES) coordination. METH-ODS: Provocative pharyngo-esophageal motility studies were performed using a water per-fused pneumohydraulic micromanometric system with a catheter assembly comprising of apharyngeal infusion port, UES and lower esophageal sphincter sleeves, and channels for thepharynx, esophageal body, and stomach. Control data from 10 orally feeding infants studiedat 39.7 ± 2.8 wks postmenstrual age (PMA) were compared with data from 25 infants withHIE studied at 41.9 ± 2.9 wks PMA. Median APGAR scores for the Control vs. HIE groupsrespectively were 6 vs. 1 at 1 minute (P<0.01), and 8 vs. 3 at 5 minutes (P<0.01). A totalof 240 (69 from controls and 171 from HIE) graded volumetric pharyngeal infusions ofsterile water (0.1ml, 0.3mL, 0.5mL, all in triplicate) were analyzed for pharyngeal, UES,and respiratory interactions. RESULTS: Although the timing and duration of the infusedstimuli were similar in both groups, the responses were distinct (Table 1). The responselatency to the onset of terminal swallow correlated highly with the duration of the respiratorychange to restoration (r=0.93, P<0.05). Relationship between infusion volume and thecontraction magnitude of pharyngo-UES contractile reflex (PUCR) was similar. However,pharyngeal swallow frequency increased with increment of infusion (P<0.01) in controlsonly, but not so in infants with HIE (P=0.6). CONCLUSIONS: Contrasting with controls,infants with Hypoxic Ischemic Encephalopathy exhibit following malfunctions: 1) Dysfunc-tional central swallowing generation, both in terms of frequency and characteristics, contribut-ing to the mechanisms of dysphagia. 2) Heightened UES resting pressures and increasedoccurrence of PUCR in response to the infusion. This increased tonicity and reactivity ofthe UES leads pooling of secretions at the pharyngeal level, as well as delayed esophagealclearance. 3) Significant prolonged disturbances in respiratory rhythm in response to pharyn-geal provocation are suggestive of aerodigestive maladaptation. Finally these findings impli-cate supranuclear or nuclear level lesions in HIE infants, that may modify the functions ofVagal and respiratory neural pathways involved with swallowing, respiration and aerodiges-tive protection. *Supported in part by 2RO1DK 068158 (Jadcherla)Table 1. Effect Of Pharyngeal Provocation On Proximal Aero-Digestive Interaction Kinetics

Data are stated as % or mean ± SEM. PRS- Pharyngeal reflexive swallow, PUCR- pharyngo-UES contractile reflex, #- Number of responses per stimulus

Tu1998

Inter-Swallow Variability Assessed by Means of Automated ImpedanceManometry Is Different in Patients With Oropharyngeal Dysphagia Comparedto Healthy VolunteersClaudia Liesenborghs, Charlotte Scheerens, Margot Selleslagh, Eddy W. Dejaeger, TaherOmari, Jan F. Tack, Nathalie Rommel

Background An important factor in the assessment of oropharyngeal dysphagia (OD) is thechallenge of inter-swallow variability. This concerns the variation between swallows withinone investigation (e.g. the influence of fatigue after multiple swallows) as well as the variationbetween investigations at different moments in time (e.g. fluctuating alertness in dementiapatients). Automated Impedance Manometry (AIM) is an objective, non-radiological tech-nique to assess pharyngeal and upper esophageal sphincter (UES) (dys)function duringdeglutition. In this study we aimed to compare the inter-swallow variability during a singleinvestigation in OD patients versus healthy controls by means of the AIM resulting pressure-flow parameters. Methods We studied 43 patients (21 males, mean 62y, range 16-90y)referred for videomanometric assessment with OD complaints and 12 healthy volunteers (6males, mean 28y, range 22-50y). All subjects underwent impedance manometry assessmentusing a high resolution solid-state catheter with 36 pressure sensors spaced at 1cm and 12or 16 impedance channels spaced at 2cm. Each subject performed 3 or 4 liquid swallowsof 5 or 10ml (bolus volume controlled within subject). Impedance manometry data wereanalyzed using AIM analysis resulting in numerical pressure-flow parameters. Bolus swallowsinterquartile ranges for each parameter were calculated per subject as a measure of individualinter-swallow variability. The interquartile ranges of the patients with OD were evaluatedagainst those of healthy volunteers by comparing median interquartile ranges per groupusing the Mann-Whitney U test (Table 1). Results For 5 out of the 12 swallow parametersassessed, median interquartile ranges significantly differed between patients and healthy

S-894AGA Abstracts

volunteers. Notably, 4/5 of these parameters were pressure-flow metrics combining informa-tion of both impedance and manometry measurements. Two global parameters, indicativeof prediction of aspiration risk (Swallow Risk Index) and post swallow bolus residue (Inte-grated nadir impedance to impedance ratio) respectively, demonstrated greater variation inpatients compared to healthy volunteers. Our data also show that with repeated swallows,pharyngeal and UES compliance is more variable in OD patients compared to controls(Pharyngeal and UES pressure at Nadir Impedance and UES Nadir Pressure). ConclusionIn this study we used pressure-flow analysis to demonstrate that inter-swallow variabilityis larger in oropharyngeal dysphagia patients compared to healthy volunteers. Consequently,deglutition of multiple boluses during a swallow examination is necessary to obtain reliableinformation on swallow function by means of impedance manometry assessment. As thismethodology is non-radiological, repeated measurements can be easily implemented.Table 1. Interquartile ranges calculated for 3 or 4 swallows per subject presented as Medians[Quartile 1 - Quartile 3]. P-values for the Mann-Whitney U Test are listed with significantp-values that survived Bonferroni correction marked with *.

Tu1999

Feasibility Model of Concurrent Pharyngeal Provocation and High ResolutionManometry (HRM) in Human NeonatesPreceousa S. Jensen, Xiaoyu Gao, Sudarshan Jadcherla

BACKGROUND: The pharynx is a site of constant stimulation throughout the suck-swallowprocess necessary for successful oral feeding. With the advent of HRM, multi-dimensionanalysis of basal swallow characteristics has been possible. Although the pharyngo-esophagealadaptive responses to pharyngeal stimulus has been shown by us using conventional waterperfusion manometry in neonates, feasibility and characterization of such responses usingconcurrent pharyngeal provocation with HRM have not been performed in human neonates.AIMS: To determine the feasibility, safety, and characteristics of concurrent pharyngealprovocation induced motility changes with HRM in human neonates METHODS: 10 neuro-logically normal infants (4 males, born at 34.0 (31.3 - 36.3) wks) were evaluated at 44.5(41.5 - 46.8) wks post-menstrual age using HRM, respiratory inductance plethysmographyand nasal airflow thermister to demonstrate a feasibility model of concurrent pharyngealprovocation and HRM. The pharyngeal infusion catheter was juxtaposed with HRM catheter.Pharyngeal and respiratory responses to graded volumes (0.1 mL, 0.3 mL, and 0.5 mL)of pharyngeal infusions are reported. Pharyngeal characteristics analyzed were pharyngealreflexive swallowing (PRS) vs. pharyngo-upper esophageal sphincter contractile reflex (PUCR)and number, duration and frequency of pharyngeal peaks in response to the incrementalvolume provocations. Distal contractile integrity (DCI), distal latency (DL), and contractilefront velocity (CFV) were used to analyze esophageal body propagation. Upper esophagealsphincter (UES) and lower esophageal sphincter (LES) were evaluated using the IntegratedRelaxation Pressure (IRP), in addition to characterization of deglutition apnea and respiratoryrate changes. Statistical analysis was performed using linear mixed models, GEE models andANOVA. Data are presented as median (IQR) or mean ± SE. RESULTS: Overall, there were72 analyzable pharyngeal water infusions. PRS is the most common response (See Table 1).The rate of LES relaxation increases with incremental volume infusions (IRP 1s, 2s, 3s, 4s,5s p<0.05). However, UES relaxation in relation to increasing volumes were similar (IRP0.2s, 0.4s, 0.6s, 0.8s, 1s p-value >0.05). Volume of infusions had no effect on the occurrenceof deglutition apnea or respiratory rate changes (p-value > 0.3) but increased volumeinfusions resulted in increased duration of both deglutition apnea and respiratory rate. Nocardiorespiratory adverse events occurred during the study. CONCLUSIONS: Concurrentpharyngeal provocation and HRM are feasible and safe in human infants. Analyses of UES,esophageal body, and LES characterization can therefore be used to distinguish adaptivepharyngo-esophagea l ref lexes in hea lth and disease. *Supported in part by2RO1DK068158 (Jadcherla)Table 1. Pharyngo-esophageal and Respiratory Responses to Pharyngeal Provocation

Data are stated as median (IQR) or mean + SEM. +0.1 mL vs. 0.3 mL infusions with p<0.05, ‡0.1 mL vs. 0.3 mL vs. 0.5 mL with p<0.05

Tu2000

Mechanism of UES Relaxation Initiated by Gastric Air DistensionIvan M. Lang, Bidyut K. Medda, Reza Shaker

The mechanism by which air distension of the stomach leads to relaxation of the UES isunknown. AIM: To test the hypothesis that transient UES relaxation (TUESR) due to gastricair distension is secondary to activation of esophageal receptors caused by gastric gasescape. Methods: Decerebrate cats (N=10) were implanted with EMG electrodes on thecricopharyngeus (CP) to record UES tone, and a strain gauge on the lower esophagealsphincter (LES) to record LES tone. A gastric fistula was formed for the injection of air ora balloon into the stomach. The effects of the following procedures on gastric distensioninduced transient relation of the LES (TLESR) and TUESR were tested: gastric balloondistension, restriction of gastroesophageal (GEJ), or venting air from the distal esophagus.RESULTS: We found (N=5) that distension of the stomach with air (mean + SE= 65+ 10ml) caused TLESR and TUESR. On the other hand, distension of the stomach with up to150 ml of air in a non-distensible balloon (N=3) activate TLESR, but not TUESR. Restrictionof the GEJ during air inflation (75 ml) of the stomach blocked TUESR, but not TLESR (N=4). Venting the distal esophagus of air prevented air distension induced TUESR (N=3).CONCLUSIONS: TUESR is not related to gastric distension or any reflex associated withgastric distension, it is due gas escaping the stomach during the TLESR. This gas escapestimulates appropriate receptors in the esophagus causing the TUESR. Prior studies havefound that air distension of the esophagus activates rapidly adapting mechanoreceptors ofthe esophageal mucosa activating eructation which includes TUESR.

Tu2001

The Impedance Analysis Using High-Resolution Impedance Manometry Underthe 1500 KOhms of Impedance Bar Facilitates Assessment of PharyngealResidue in Patients With Oropharyngeal DysphagiaTae Hee Lee, Joon Seong Lee, Su Jin Hong, Seong Ran Jeon, Wan Jung Kim, Hyun GunKim, Jun-Hyung Cho, Mi Young Kim, Joo Young Cho, Jin-Oh Kim

Background: Recently we reported that HRIM-based qualitative impedance assessment ena-bled recognition of pharyngeal residue. However this is a small sample sized study witharbitrary criteria for color impedance. Subjects and Methods:Pharyngoesphageal bolus transitswere evaluated with an impedance contour pattern (linear vs. stasis) method in both healthysubjects (n=33) and patients (n=104). We compared the pharyngeal residue on fiberopticendoscopic evaluation swallowing study and impedance contour pattern under the value of1000, 1500 and 2000 KOhms of the impedance bar. The sensitivity and specificity weremeasured and compared among the three criteria of impedance bar. We also evaluated theinterobserver agreement among the three gastrointestinal fellows (non-experts) after provid-ing 1-hour education about the impedance analysis Results: Diagnostic sensitivities forpredicting for pharyngeal residue during the liquid swallow were 73.1%, 96.2% and 100%under the values of 1000, 1500, and 2000 KOhms, respectively. A significant differencewas observed in the sensitivity between 1000 KOhms and the other criteria (P<0.05).Specificities were 98.3%, 96.6%, and 83.1% under the values of 1000, 1500, and 2000KOhms, respectively. There was a significant difference in the specificity between 2000KOhms and the other criteria (P<0.05). The kappa values for interobererver agreementamong the three fellows were 0.89. Conclusions:Qualitative HRIM-based impedance contourpattern analysis under the 1500 KOhms of the impedance bar acceptably provides diagnosticsensitivity and specificity for predicting pharyngeal residue during liquid swallow.

S-895 AGA Abstracts

Tu2002

Effect of External Anterior Cervical Pressure Location on the UES High-Pressure Zone Is Site SpecificLing Mei, Hongmei Jiao, Tarun Sharma, Patrick Sanvanson, Sudarshan R. Jadcherla, RezaShaker

Introduction: External cricoid pressure has recently been used to augment the upperesophageal sphincter (UES) pressure in order to prevent esophago-pharyngeal reflux inpatients with supraesophageal complications of reflux disease. UES high-pressure zone (HPZ)in addition to cricopharyngeal muscle (CP) perceives contribution from inferior pharyngealconstrictor (orad to CP) and proximal esophagus (caudad to CP). However, the effect ofpressures applied to sites orad and caudad to the cricoid cartilage is not known. Thisinformation may have practical implications in using UES pressure augmentation techniquesin clinical practice. Aim: To determine and compare the effect of pressures applied to cricoid,supra-cricoid and infra-cricoid region on the length and amplitude of the UES HPZ. Methods:We studied 11 patients (5 male, 57.8 ± 11.6 years) with various supraesophageal refluxsymptoms. The external pressures were applied perpendicularly to the center of the cricoid,1 cm proximal (supra-cricoid), and 1 cm distal to the cricoid (sub-cricoid), using handmadelaboratory device comprised of a small pressure cushion (0.8 cm x 0.5 cm x 2.5 cm) fortargeting the pressure to a specific site. Externally applied pressures were monitored usinga specially designed pressure gauge (SomnaTherapeutics, Glendale, WI). We tested 0, 20,30, 40 mmHg pressures by pressing the cushion perpendicularly with the index finger andmaintained for 10 seconds to the selected sites. Each pressure application was repeated 3times. UES, pharyngeal and proximal esophageal pressures were determined using high-resolution manometry. Results: The length of the UES-HPZ increased from baseline (zeroexternal pressure) of 2.2±0.3 cm to 3.2±0.2 cm, 3.1±0.2 cm and 2.9± 0.2cm in responseto cricoid, supra-cricoid and sub-cricoid pressure, respectively (p<0.05). When applyingexternal pressure to the middle of cricoid, the expansion of the UES-HPZ was relativesymmetric. However, the increase of the length of the UES-HPZ was more orad when thepressure was applied at the supra-cricoid level. The caudad expansion was observed whenthe pressure was applied at the sub-cricoid level (figure). The magnitude of pressure increasewas greatest at the middle and orad part of the UES HPZ when the external pressure wasapplied at the cricoid and supra-cricoid levels, respectively. However, the correspondingmagnitude of increase in the caudad part of the UES HPZ was not observed when theexternal pressure was applied at the sub-cricoid level (table). Conclusions: While externalpressure affects both length and magnitude of UES HPZ, its effects are site dependent.Application of external pressure at the sub-cricoid level has the least effect on UES HPZcompared to pressures applied to cricoid and supra-cricoid level.UES pressure increase in response to location of external pressure (mean pressure increase± SE)

* UES_0: upper border of UES, UES_1: 1cm below UES_0, UES_2: 2cm below UES_0,UES_3: 3cm below UES_0

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