Introduction: Delayed gastric emptying (DGE) often occurs in patients with gastroesophageal reflux (GER) due to neurological impairment (NI). 13C has been used as an alternative tool for measuring the gastric emptying rates. The aim of this study was to predict gastric emptying in children with GER using 13C-acetate breath test (ABT) by 24-hour pH monitoring. Methods: Nineteen patients were divided into 2 groups: a DGE group with NI (14 patients), and normal-emptying group without NI (5 patients). The liquid test meal consisted of RacolTM (5 ml/kg) mixed with 13C-acetate (50 mg for infants, 100 mg for children, and 150 mg for adolescents). 13CO2 was measured using a gas chromatograph-isotope ratio mass spectrometer. The results are expressed as the % of 13C expired per hour and cumulative 13C excretion over a 3-hour periods including the parameters of half excretion and lag time. Results: The mean half excretion time was 1.762 hour in the DGE group and 1.095 hour in the normal-emptying group (P = 0.0196). The mean lag time was 0.971 hour in the DGE group and 0.666 hour in the normal-emptying group (P = 0.0196). Therefore, DGE was significantly more prevalent in the DGE compared to the normal-emptying group. The percentage of the time when the pH was less than 4 on 24-hour esophageal pH monitoring was 21.6% ± 9.2% in the DGE group and 28.5% ± 11.6% in the normal-emptying group (P = 0.4634). Conclusion: The percentage of time when the pH is less than 4 on 24-hour pH monitoring cannot predict DGE measured by the 13C-ABT in GER.
Delayed gastric emptying (DGE) is often observed in children with gastroesophageal reflux (GER) [1,2]. The etiology of DGE is related to motility disorder of the antrum and occasionally of the entire stomach [
Recently, 13C has been used as an alternative tool for measuring the gastric emptying rates of both solids and liquids [4-6]. 13C is a stable, naturally occurring, nonradioactive isotope that can easily be detected by mass spectrometry [
We previously showed that children with NI exhibited DGE differing from that found in those without NI [
Between April 2002 and March 2011, 19 patients with symptomatic GER were admitted to our institution and diagnosed by upper gastrointestinal studies and 24-hour esophageal pH monitoring. Patients did not undergo operations such as the antireflux procedure. We previously showed that children with NI exhibited DGE differing from that found in those without NI [
None of the patients in the DGE or normal-emptying group received any medication with a potential influence on gastrointestinal motility during the study, excluding anticonvulsants. Drugs for gastrointestinal motility and H2 blockers stopped for 3 days. Informed consent to perform 24-hour esophageal pH monitoring and the 13CABT was obtained from the parents.
The 24-hour esophageal pH monitoring was performed with a Digitrapper Mk Ⅲ (Medtronic, Copenhagen, Denmark) device. The correct positioning of the probe above the esophagogastric junction was verified by fluoroscopy. On pH monitoring, the signal was sampled every 4 seconds, and a drop in pH below 4 lasting at least 20 seconds was considered a reflux episode. The 24-hour esophageal pH monitoring was considered pathologic if the total recorded time for which the pH was <4 was more than 4% (percentage of time the pH was less than 4) [
All children fasted 2 hours for liquids and 6 hours for solids prior to 13C-ABT. RacolTM (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was used as the test meal and was administered at 5 ml/kg (maximum dose: 200 ml). The nutrient composition of 100 ml of RacolTM (100 kcal) is 4.4 g of protein, 15.6 g of carbohydrates and 2.2 g of fat. 13C was used to label acetate (99%; Cambridge Isotope Laboratories, Woburn, MA, USA), which is absorbed in the duodenum but not in the stomach. RacolTM was mixed with 13C-acetate (50 mg for infants, 100 mg for children, and 150 mg for adolescents) [
Breath samples were collected for 13CO2 measurement before the intake of the meal, every 15 minutes during the first 2 hours after the meal, and every 30 minutes thereafter for ingestion of 13C-acetate and RacolTM [
During each expiration phase, exhaled air was collected into a bag using a modified face mask or tracheostomy tube 11 times in all. It took about 1 minute to collect the exhaled air into one bag. 13CO2was measured using a gas chromatograph-isotope ratio mass spectrometer (UBiT-IR300, Ootsuka Electronic Corp). For the 13C-ABT, the concentration of 13CO2 (the final product in exhaled air) was measured. The results are expressed as % of 13C expired per hour and %13CO2 cumulative excretion over a 3-hour period.
The %13CO2 cumulative excretion in the breath was assessed using a nonlinear regression formula:
The Mann-Whitney U test was used to evaluate the significance of differences of each parameter of the 13CABT and percentage of time when the pH was less than 4 of 24-hour esophageal pH monitoring between DGE and normal-emptying groups.
The half excretion and lag times of individual patients are shown in
Patients with NI have a high incidence (up to 15%) of
GER [
The various diagnostic modalities available for GER include barium swallow, radionuclide scintigraphy, 24-h esophageal pH monitoring, and endoscopy. In the present study, pH-metry was used as a prognostic tool to detect clinically significant GER. Bergmeijer et al. [
13C-ABT parameters such as the half excretion and lag times were significantly different in all children with GER associated with NI in this study. Furthermore, the percentage of time the pH was less than 4% on 24-hour esophageal pH monitoring was 21.6% ± 9.2% in the DGE group and 28.5% ± 11.6% in the normal-emptying group, with no significant difference. Therefore, this study verified that the parameter of the percentage of time the pH is less than 4 (esophageal acid exposure time) was not useful to predict DGE. Our findings suggest that DGE measured by 13C-ABT parameters such as the half excretion and lag times was not related to esophageal acid exposure on 24-hour esophageal pH monitoring, which was significantly different in all children with GER associated with NI. The reasons for these results were speculated to be due to good esophageal clearance, neutralization of gastric acid by bile due to duodenogastric reflux, or the influence of the post prandial state and fasting [15,16]. Although unexpected, this correlates with the findings of José Estevão-Costa et al., where by the percentage of time the pH was less than 4% in the DGE group (12.3%) was not significantly different from that in the normal-gastric emptying group (23.7%). Similar to our findings, the percentage of time the pH is less than 4% one esophageal 24-hour pH monitoring cannot be used to predict DGE measured by the 13C-ABT in GER patients with NI (DGE group). Therefore, these series suggest that DGE is not a marker of severe GER.
Our study involving esophageal 24-hour pH monitoring was performed without distinguishing the postprandial state from the fasting one. The stomach may indirectly contribute to GER [
One limitation of this study was that the mean age in DGE and normal-emptying groups was 4.2 and 10.0 years, respectively. This wide age variation between DGE and normal-emptying groups might have influenced our results concerning gastric emptying. The choice of test meals also warrants some discussion, including the fact that the use of the 13C-ABT may limit the choice to liquids.
Although the number of cases in this study is too small to draw any conclusion, a tendency that the percentage of time when the pH is less than 4 on 24-hour pH monitoring cannot predict DGE measured by the 13C-ABT in GER was recognized. Larger studies are required to determine the accuracy of the esophageal 24-hour pH monitoring which cannot predict the delayed GET.
We showed that the rate of gastric emptying could be measured by the 13C-ABT in patients with GER associated with and without NI, and that the percentage of time when the pH is less than 4% on esophageal 24-hour pH monitoring cannot be used to predict DGE measured by the 13C-acetate breath test in GER.
The authors declare that they have no competing interests.
The authors thank Drs. Manabu Nakagawa, Mototsugu Kato, Masahiro Asaka and Yumiko Tsuda for her excellent technical assistance.