Relevance of ineffective esophageal motility (IEM) during esophageal acid clearance

432

434

Tegaserod Improves Gastric Emptying in Patients with Gastroparcsis and Dyspeptic Symptoms Gervais Tougas, Ying Chen, Don Luo, Janeen Salter, Tara D'Elia, David L. Earnest

Acid secretion of reflux esophagitis and other upper gastrointestinal diseases in Japanese Tomoyuki Koike, Shuichi Ohara, Katsunori lijima, Hitoshi Seknie, Yasuhiko Abe, Yoshifumi lnomata, Masashi Kawamura, Naohiro Dairaku, Akira Imatani, Katsuaki Kato, Tooru Shimosegawa

BACKGROUND: Tegaserod (T) is a 5HT4 receptor partial agonist with prokinetic properties. T is approved for treatment of irritable bowel syndrome with constipation. Recently, the approved dose (6mg bid) of T was reported to also increase the rate of gastric emptying (GE) in healthy men (L. Degan, Aliment Pharmaco[ Ther 2001;15:1745-1751). To evaluate whether T can also improve abnormally delayed GE, we studied the effects of different doses of T in patients with dyspeptic symptoms who had delayed GE. METHODS: In a double blind, placebo controlled study, we evaluated the effects of T on GE in 163 patients with gastroparesis and dyspeptic symptoms. Abnormal GE was documented at baseline by scintigraphy using a 99mTc-labeled standard egg substitute meal. Delayed GE was defined as gastric retention (GR) of greater than 6.3% of the test meal at 4 hours. Subjects were then randomized to: T 6mg bid (n=38), T 6rag tid (n=24), T 12rag bid (n=38) or to placebo (P; n=63). After 8 weeks of treatment, GE was again quantitated by scintigraphy at I, 2 and 4 hours using the same method. RESULTS: GR of the test meal at baseline and after 8 weeks of treatment (total daily doses of T were 12rag, 18mg, 24rag) is shown in the Table. GR was consistently reduced by T, especially at 2 and 4 hours after the meal. Although GR was also decreased with P, treatment with T at 18rag and 24rag/day decreased food retention in late phase emptying by about two-fold. In fact 80% of patients given 18rag/ day developed normal GE compared to only 50% of those given P (p less than 0.058). CONCLUSION: T improves GE in patients with gastroparesis and dyspeptic symptoms.

Background and Aims: We have reported that prevalence of H.pylori (HP) infection and grade of atrophic gastritis were significantly lower, while acid secretion was significantly greater in the patients with reflux esophagitis (RE) than those without RE. (Gut 2001; 49:330-334). We have also reported that increased gastric acid secretion after kip eradication may provide a reason for developing RE (Aliment Pharmacol Ther 2001; 15:813-820). However, there have been few studies that compared acid secretion of RE with that of other upper gastrointestinal diseases in Japanese. The aim of this study was to investigate acid secretion of RE and other upper gastrointestinal diseases. Subjects and Methods: One hundred five patients with RE (59 men(M)/46 women(W); mean age 56.2 years, HP positive rate: 34.3%), 57 gastric ulcer (GU) (48 M/9 W; mean age 53.6 years, HP positive rate: 100.0%), 50 duodenal ulcer (DU) (39 M / 11 W; mean age 37.8 years, UP positive rate: 100.0%), 24 early gastric cancer (EGC) (18 M / 6 W; mean age 64.5 years, HP positive rate: 100.0%), 132 HP positive gastritis (69 M / 63 W; mean age 54.7 years) and 89 HP negative control subjects who had no lesions in the upper gastrointestinal tract on endoscopy (41 M / 48 W; mean age 43.1 years) were enrolled in this study. The diagnosis of HP infection was made by histological examination of gastric mucosal biopsy specimens, RUT and detection of serum IgG antibodies. Acid secretion was assessed by endoscopic gastrm test (EGT) (Am J Gastroenterol 1998; 93:2113-2-118). Results: EGT value (mEq/10min) of the patients with upper gastrointestinal diseases were the following; RE: 3.65_+2.17, GU: 2 . 8 9+- 1.81, DU: 4.93 +-2.48, EGC: 0.44 + 0.58, HP positive gastritis: 1.49 _+ 1.40, HP negative control: 3.05 -+ 1.47. Acid secretion of DU was significantly greater than that of UP negative control subjects (p<0.01). Acid secretion of RE was significantly greater than that of HP positive gastritis patients (p<0.01). However, it was not significantly different between RE patients and UP negative control subjects. On the other hand, acid secretions of EGC patients and HP positive gastritis patients were significantly lower than acid secretion of HP negative control subjects (p
TaMe: Mean Gutrlc RetentJon(Percent) of Meal at 1, 2, and 4 Hours by TreaMzent 2Hr

4Hr

T24m9 T18rng T12m9 Baxline (per. ctnt) 8 Weeks (per-

cent)

Reduction from Baseline (Percent)

P

T24mg T18mg

T12m9

P

50

58

52

53

18

21

17

18

38

38

44

50

6

6

11

11

24

35

15

6

67

71

35

38

433 435 Esophagogastric Junction (EGJ) Morphology Predicts Susceptibility to Exerciseinduced Reflux Laura K. Bianchi, John E. Pandoffino, Kelly Goelz, Thomas J. Lee, Peter J. Kahrilas

Relevance of ineffective Esophageal Motility (IEM) During Esophageal Acid Clearance Magnus Simren, Jiri Silny, Richard H. Hofloway, Jan Tack, Jozef Janasens, Daniel Sifrim

Aim: Although strenuous exercise has been reported to increase gastroesophageal reflux, little data exists exploring the determinants of this relationship. The aim of this investigation was to quantify esophageal acid exposure during exercise using a radiotelemtry pH moaitoring system in subjects with varying stages of EGJ disruption. Methods: Ten controls and 10 endoscopy negative GERD patients (ages 22 to 44, 11 male) were studied for a two day period using the Bravo pH monitoring system. The pH capsule was placed 6 cm above the SCJ. The subjects were randomly assigned to perform 60 minutes of exercise on day 1 or 2 consuming the exact same diet on both days. Exercise consisted of 30 minutes of running and 30 minutes of 5 resistance exercises. Subjects underwent endoscopy to grade the EGJ morphology according to the flap valve concept: (I) normal ridge of tissue closely approximated to the scope; (11) ridge is slightly less well defined and opens with respiration; (11 I) ridge is effaced and the hiatus is patulons and (IV) hiatus is wide open at all times and displaced axially. Results: Nineteen subjects completed the two-day study with 100% data capture during exercise. One failure was related to poor data reception. There was a significant increase in % time the pH < 4 in the GERD patients compared to controls during each time period studied (Table). Median acid exposure was increased more than threefold during exercise when compared to the median 48 hour acid exposure for both controls and G E RD patients. The EGJ morphology grades were significantly lower in controls compared to GERD (NL; I-3, 11-6, GERD; I[-3, II[-5, IV-2, p<0.005). In addition, there was a strong correlation between EGJ grade and % time p H < 4 during exercise (Table). Conclusions: Exercise caused a threefold increase in esophageal acid in both normal subjects and GERD patients. The degree of exercise-induced gastroesophageal reflux is correlated with EGJ morphology grade and this supports the hypothesis that anatomi ca[ integrity of the EGJ is important in preventing exercise-induced reflux.

Esophageal clearance of acid reflux consists of an initial volume clearance followed by neutralization of the acidified mucosa by swallowed saliva (chemical clearance). Ineffective esophageal motility (IEM), a frequent finding in patients with gastroesophageal reflux disease (GERD), has been chimed to underlie prolonged acid clearance by affecting esophageal emptying and saliva transport. Intrahiminal impedance allows a non-radiological monitoring of esophageal bquids movement and can be used to assess volume clearance. We aimed to evaluate the relevance of IEM during esophageal volume and chemical clearance using combined pH-impedance measurements. Methods: Acid clearance tests were performed in 10 healthy subjects in upright and supine position, before and after esophageal peristaltic disruption with sfldenafil (50mg). After instillation of an acid bolus, simultaneous manometry, pH and impedance were used to study esophageal motility, chemical clearance and volume clearance respectively. The degree of impairment of esophageal motility was divided into 3 levels: normal motility (<30% of peristaltic sequences abnormal), moderate IEM (30-80% abnormal peristalsis) and severe IEM (>80% abnormal peristalsis). Results: SildenafiI provoked a graded impairment in esophageal motility without affecting saliva secretion. In upright position, the volume clearance was significantlyprolonged with severe IEM compared with normal motility (101 _+46 sec vs. 57 +- 18 sec; p<0.05). The chemical clearance however, was not significandy affected by IEM. In supine position, severe IEM prolonged significantly both chemical (CC) and volume clearance (VC) compared to normal motility (CC: 480_+ 284 vs. 183"4"125 sec; p<0.01. VC:145 + 84 vs. 42 + 18 sec; p
Tt~e

liedla. %tim pH< 4 Patients(n) NL(9) (t'~%)

Total 2.4(4.2)

Updght 2.6(5.7)

Sum* 0.2(1.9)

PP 3.4(6,8)

GERD(10)

5.2(3.1)#

6.4(4.7)#

1.2(1,2)#

5.7(6.5)#

CondaUtm wRhE~

r=0.59(P-~.005) r=O.Sg(P=O.O05) '"~'n~"=

Exerc~e 9,2(10,3)"

436

17.4(H.1)~

Mechanisms of Gastroesophageal Reflux in Critically Ill Mechanically-Ventilated Patients Garry Nind, Wei-Hao Chen, Katsuhiko lwakiri, Duo Wu Zou, Robert J. Fraser, Robert Young, Daniel Sifrim, Rachel Rigda, Richard H. Hofloway

r=0,51(P=0.02) r=O.75{P
w,~ 09)

"P <0.05vs allo~er tirnes,# P <0.05vscontrol

Gastroesophageal reflux is a major problem in mechanically vemilated patients in ICU and may lead to pulmonary aspiration and erosive esophagitis, both of which are associated with morbidity and mortality. Transient lower esophageal sphincter relaxations (TLESP,s) are the most common mechanism underlying gastroesophageal reflux in non-ventihted patients. In critically ill patiems it has been shown that their esophageal clearance of refluxed material is impaired due to diminished and ineffective esophageal motility, but the mechanisms that underlie gastro-oesophageal reflux in this group have not been studied. Aims. To determine the mechanisms underlying gastroesuphageal reflux in mechnically-ventilated patiems in ICU using combined esophageal pH monitoring ind multiple intrahimina] impedance (MII). Methods. In 15 mechanically ventilated ICU patients (12M 3F, median age 55 yr (23-77 yr), median 1CU stay 6 days (range 3-12 days)) we recorded esophageal motility pH and

AGA Abstracts

A-54