Validation of a stable isotope gastric emptying test for normal, accelerated or delayed gastric emptying

To validate a 13C-Spirulina platensis breath test for measurement of accelerated or delayed gastric emptying, we measured gastric emptying of egg containing 13C-S. platensis and 99mTc-sulphur colloid by breath 13 CO2 every 15 min over 3 h and scintigraphy every 15-30 min over 5 h in 57 healthy volunteers. Thirty-three received no treatment, 10 received erythromycin, and 14 atropine. A generalized linear regression model predicted half-emptying time by scintigraphy (t1/2S) from breath 13CO2 (t1/2B) data. Accuracy was assessed by standard deviation (SD) of differences between t1/2S and t1/2B and by receiver operating characteristic (ROC) curves. Regression models using breath samples at baseline, and 45, 90, 105 and 120 min, predicted t1/2B (mean +/- SD) at 118 +/- 59 min, similar to t1/2S (118 +/- 67 min). Correlation between t1/2B and t1/2S was significant (r=0.88; P < 0.0001). Differences between t1/2S and t1/2B were: 18-19.2 min for t1/2 < 70-150 min, and 68.3 min for t1/2 > 150 min. Breath test detected abnormal emptying with a sensitivity of 86% and specificity of 80%. Thus, the 13C-S. platensis test measures gastric emptying t1/2 for solids, which is accelerated or delayed to mimic a range of conditions from dumping syndrome to severe gastroparesis, with high sensitivity and specificity. Additional breath samples are needed to increase sensitivity in detecting accelerated gastric emptying.     

Indirect vs direct assessment of gastric emptying: A randomized crossover trial comparing C‐isotope breath analysis and MRI

Background

Indirect methods to assess gastric emptying (GE), such as ¹³C breath tests (BT), are commonly used. However, BT usually use a sampling time of 4+ hours. The current study aims to assess the validity of BT for four liquid meals differing in physicochemical properties. To this aim, we compared them to MRI GE‐measurements.

Methods

Fifteen healthy males (age 22.6 ± 2.4 years, BMI 22.6 ± 1.8 kg/m²) participated in a randomized 2 × 2 crossover experiment. Test foods were liquid meals, which were either thin/thick and 100/500 kcal, labeled with 100 mg of ¹³C‐octanoate. GE was measured with MRI and assessed by ¹³C recovery from breath. Participants were scanned every 10 minutes and at six time points breath samples were collected up to t = 90 minutes. Two curves were fitted to the data to estimate emptying halftime (t_{50 Ghoos} and t_{50 Bluck}). T₅₀ times were ranked per participant and compared between methods.

Key Results

On average, MRI and BT showed similar t₅₀ rankings for the four liquid meals. In comparison to MRI, t_{50 Ghoos} overestimated, while t_{50 Bluck} underestimated GE time_. Moreover, more viscous foods were overestimated. In most participants individual t₅₀ time rankings differed significantly between methods.

Conclusions & Inferences

BT can assess relative emptying differences on group level and collecting breath data for 90 minutes constitutes a lower burden for participants and the research facility. However, BT has severe shortcomings compared to MRI for individual GE assessment. Notably, food matrix effects should be considered when interpreting the results of BT.     

Optimizing analysis of stable isotope breath tests to estimate gastric emptying of solids

Abstract  Breath tests (BT) using ¹³C–substrates have been proposed for the measurement of gastric emptying (GE). The mathematical analysis of the breath ¹³CO₂ excretion that most accurately predicts GE t _1/2 from simultaneous scintigraphy is unresolved. To compare five mathematical methods to estimate GE t _1/2 by BT with t _1/2 from simultaneous scintigraphy. Data acquired from a dual-labelled solid–liquid meal containing ^99mTc sulphur colloid and ¹³C- Spirulina platensis from 57 healthy volunteers were used to compare four mathematical methods reported in the literature [Ghoos method; generalized linear regression (Viramontes); linear regression (Szarka); Wagner–Nelson method] and the total cumulative breath ¹³CO₂ excretion with ≥12 breath samples collected over at least 4 h. The concordance correlation coefficient (CCC) for the t _1/2 results obtained with each method using BT data was compared with the results obtained with scintigraphy. The linear regression and generalized linear regression methods used five samples at 45, 90, 120, 150 and 180 min. All methods, except for the Wagner–Nelson method, resulted in mean GE t _1/2 that approximated t _1/2 obtained with scintigraphy. The highest CCC was observed with the linear regression method. Simple cumulative excretion of breath ¹³CO₂ provides a better CCC than the Ghoos method. The linear regression and generalized linear regression methods (which also require relatively few breath samples) provide the most accurate analyses of breath ¹³CO₂ excretion in stable isotope GEBT.     

Will the 13C‐octanoic acid breath test ever replace scintigraphy as the gold standard to assess gastric emptying?

Abstract  The applicability of the ¹³C-octanoic acid breath test for the assessment of gastric emptying is discussed. In the current issue of this journal, Keller and her colleagues described the application of different mathematical models for analysis of the ¹³C-octanoic acid test in a very large patient population.     

Spectrum of gastric emptying patterns in adult patients with cyclic vomiting syndrome

Background Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom‐free intervals. Both rapid and delayed gastric emptying (GE) have been observed but the reports involved small numbers of CVS patients. Methods We performed a retrospective study of 92 adult patients who met Rome Ш diagnostic criteria for CVS between 2003 and 2009 at the Kansas University Medical Center. Gastric emptying was measured by a standardized scintigraphic method involving a low fat (2%) isotope labeled egg white meal of 250 Kcal, with anterior and posterior gastric imaging in the standing position obtained at 0, 1, 2, 4 h after meal ingestion. Rapid GE was defined as <50% isotope retention at 1st h and/or <30% at 2nd h and delayed GE as >10% at 4 h. Key Results Ninety two patients were analyzed: 47 males and 45 females mean of age 37 ± 12 years (range: 20–68 years). There were 27 patients with a personal history of migraine headache, 30 with history of marijuana use, 12 had diabetes mellitus (DM) and 10 had irritable bowel syndrome (IBS) as an accompanying diagnosis. Fifty four patients (59%) met criteria for rapid GE, 25 (27%) had normal GE and 13 (14%) had slow GE. Eighty percent of patients with co‐existing IBS symptoms were identified as rapid. The subset with delayed emptying was often associated with narcotics use, DM and marijuana use (P < 0.05). Conclusions & Inferences (i) In adult CVS patients, GE is generally either rapid or normal. (ii) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (iii) The small subset of CVS patients (14%) whose GE was slow were explained by the role of narcotics and/or marijuana.     

Prognostic implication of gastroparesis in patients with diabetes mellitus

The prognosis and survival in 13 patients with Type II diabetes mellitus who had delayed gastric emptying as shown by radionuclide tests performed between August 1985 and August 1987 was determined in July 1990. The two patients that were over 80 years of age died within 18 months of the diagnosis of diabetic gastroparesis, but ten of the remaining eleven patients survived. The clinical data on these patients suggest that despite the usual presence of significant co-existent pathology, gastroparesis diabeticorum carries a less ominous prognosis than currently believed.     

The 13C-octanoic acid breath test: validation of a new noninvasive method of measuring gastric emptying in rats

Abstract Currently available rat models for measuring gastric emptying are hampered by the necessity to kill the animals at the end of each experiment, which makes repetitive testing impossible. We have developed and validated a noninvasive test model, adapted from the¹³C‐octanoic breath test in humans, for repetitive measurements of gastric emptying in rats. Male Wistar rats were trained on a fixed protocol to eat a piece of pancake doped with 1 μg¹³C‐octanoic acid after 12 h fasting, and to stay thereafter in cylindrical glass cages. Breath tests were performed by a fully automated system of computer‐guided switching valves, which collected consecutive breath samples. All breath samples were analysed by gas chromatography and isotope mass spectrometry. The area under the curve (AUC) from the cumulative¹³CO₂excretion from 0 to 6 h was determined by the trapezium method to calculate the gastric half‐emptying times (t½). Inter‐day variability was determined. The effect of subcutaneous or intraperitoneal injection of saline was studied. The test was further validated for pharmacological interventions by oral administration of cisapride and parenteral administration of atropine, to induce, respectively. acceleration and delay of gastric emptying. Mean gastric emptying times ± SD of 24 rats were 119.3 ± 28.2 min, 138.7 ± 26.0 min, and 124.5 ± 30.9 min on three different test days. The mean coefficient of variation of three repeated measurements in the same 24 rats was 17.5%. No significant differences were observed after subcutaneous or intraperitoneal injection of saline. In a second test series of eight rats, cisapride significantly accelerated gastric emptying (mean t½ 112.7 ± 33.1 min, P < 0.05), while atropine caused a significant delay (mean t½ 205.9 ± 24.9 min, P < 0.05) when compared to control test results (mean t½ 140.7 ± 16.7 min) in the same rats. We validated the¹³C‐octanoic breath test to study gastric emptying in rats. This test method obviates the necessity to kill laboratory animals and allows repetitive measurements of gastric emptying to study its physiology or pathophysiology as well as the effect of pharmacological agents.     

Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy

Abstract  Gastric emptying of digestible solids occurs after trituration of food particles. Non-digestible solids are thought to empty with phase III of the migrating motor complex (MMC). The aim of this study was to determine if a non-digestible capsule given with a meal empties from the stomach with return of the fasting phase III MMC or during the fed pattern with the solid meal. Fifteen normal subjects underwent antroduodenal manometry and ingestion of a radiolabelled meal and SmartPill wireless pH and pressure capsule. In five subjects, emptying of the SmartPill was studied in the fasting period by ingesting the SmartPill with radiolabelled water. The SmartPill emptied from the stomach within 6 h in 14 of 15 subjects. SmartPill pressure recordings showed high amplitude phasic contractions prior to emptying. SmartPill gastric residence time (261 ± 22 min) correlated strongly with time to the first phase III MMC (239 ± 23 min; r  = 0.813; P  < 0.01) and correlated moderately with solid-phase gastric emptying ( r  = 0.606 with T-50% and r  = 0.565 with T-90%). Nine of 14 subjects emptied the capsule with a phase III MMC. In five subjects, the SmartPill emptied with isolated distal antral contractions. In five subjects ingesting only water, SmartPill gastric residence time (92 ± 44 min) correlated with the time to the first phase III MMC (87 ± 30 min; r  = 0.979; P  < 0.01). The non-digestible SmartPill given with a meal primarily empties from the stomach with the return of phase III MMCs occurring after emptying the solid-phase meal. However, in some subjects, the SmartPill emptied with isolated antral contractions, an unappreciated mechanism for emptying of a non-digestible solid.     

Assessment of symptoms during gastric emptying scintigraphy to correlate symptoms to delayed gastric emptying

Background Symptoms of gastroparesis based on patient recall correlate poorly with gastric emptying. The aim of this study is to determine if symptoms recorded during gastric emptying scintigraphy (GES) correlate with gastric emptying and with symptoms based on patient recall. Methods Patients undergoing GES completed the Patient Assessment of GI Symptoms (PAGI‐SYM) assessing symptoms over the prior 2 weeks and a questionnaire for which patients graded six symptoms during GES. A Symptom Severity Index (SSI) represented the mean of six symptoms at each time point. Key Results A total of 560 patients underwent GES for clinical evaluation of symptoms. Of 388 patients included in the study: 232 patients had normal GES (NGES), 156 delayed GES (DGES), and 11 rapid GES (RGES). Symptom severity index increased pre to postprandial for each group: NGES: 0.51 ± 0.07 to 0.92 ± 0.03, DGES: 0.60 ± 0.09 to 1.13 ± 0.05, and RGES: 0.56 ± 0.12 to 0.79 ± 0.13. Delayed gastric emptying scintigraphy patients had a higher postprandial SSI than NGES patients (1.13 ± 0.05 vs 0.92 ± 0.03, P < 0.05). Postprandial symptoms of stomach fullness (1.9 ± 0.12 vs 1.5 ± 0.09; P = 0.011), bloating (1.4 ± 0.11 vs 1.1 ± 0.09; P = 0.033), and abdominal pain (1.1 ± 0.08 vs 0.7 ± 0.12; P = 0.012) were higher in DGES than NGES. Symptom severity based on PAGI‐SYM for 2 weeks prior to GES correlated with symptoms during the test for nausea (NGES, r = 0.61; DGES, r = 0.70), stomach fullness (NGES, r = 0.47; DGES, r = 0.60), and bloating (NGES, r = 0.62, DGES, r = 0.66). Conclusions & Inferences Stomach fullness, bloating, and abdominal pain recorded during GES were higher in patients with delayed gastric emptying than in patients with normal gastric emptying. Symptoms recorded during GES correlated with those during daily life by patient recall.     

Relationships between hypoglycaemia and gastric emptying abnormalities in insulin-treated diabetic patients.

We hypothesize that hypoglycaemia in insulin-treated diabetic patients may result from gastric emptying abnormalities causing insulin and food absorption mismatching. We tested gastric emptying in insulin-treated diabetic patients with unexplained hypoglycaemia and without dyspepsia and in diabetic patients without hypoglycaemia, prospectively. Thirty-one diabetic patients with unexplained hypoglycaemic events within 2 h of insulin injection and 18 insulin-treated diabetic patients without hypoglycaemic events underwent gastric emptying breath tests, glycaemic control and autonomic nerve function. Gastric emptying tests were abnormal in 26 (83.9%) and in four (22.2%) patients with and without hypoglycaemia, respectively (P < 0.001). Gastric emptying was significantly slower in hypoglycaemic diabetic patients (t1/2 139.9 +/- 74.1 vs 77.8 +/- 23.3 and t(lag) 95.8 +/- 80.3 vs 32.84 +/- 16.95 min, P < 0.001 for both comparisons; t-tests). A significant association between hypoglycaemic patients and abnormal values of t1/2 and t(lag) was found (P < 0.001). Gastric emptying abnormalities were more frequent in hypoglycaemic patients. We suggest gastric emptying tests for diabetic patients with unexplained hypoglycaemic events.     

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

Abstract The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and ¹³C‐acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of ¹³C‐acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half‐times (T½) for MRI and BT were calculated (mean ± SD). We found: (i) Initial GCV was lower in FD than in HC (762 ± 22 vs 810 ± 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T½_MRI was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 ± 30 min vs FD 138 ± 42 min, ns; 800 mL: HC 71 ± 16 min vs FD 78 ± 27 min, ns). In contrast, T½_BT was similar between meals and groups (200 mL: HC 111 ± 11 min vs FD 116 ± 19 min; 800 mL: HC 114 ± 14 min vs FD: 113 ± 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non‐invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high‐volume compared to low‐volume liquid nutrient meals in HC or FD.     

Comparisons of the effects of enterostatin on food intake and gastric emptying in rats

The effects of central and peripheral administration of enterostatin (ENT) on food intake and gastric emptying of a non-nutrient liquid meal have been studied in rats. Intraperitoneal and intragastric administration of ENT at a dose of 120 nmol suppressed the intake of a high-fat diet but failed to inhibit gastric emptying in Sprague-Dawley (SD) rats. Intracerebroventricular (i.c.v.) ENT (1 nmol) reduced intake of a high-fat diet in Osborne-Mendel (OM) and SD rats but not in S5B/Pl rats, whereas it decreased gastric emptying in S5B/Pl and SD rats but not in OM rats. The data suggest that although central ENT may reduce gastric emptying rate, this effect is not related to the inhibitory effect of ENT on food intake.     

A Bayesian hierarchical assessment of gastric emptying with the linear,power exponential and modified power exponential models

Background Many studies assessed gastric retention over time utilizing different models, mostly with scintigraphic measures at varied endpoints from limited number of normal volunteers. With a standardized 4‐h gastric emptying (GE) protocol, we compared model fit by the linear, power exponential (PE), and modified power exponential (MPE) models to contrast differences in GE among different groups based on clinical diagnosis and gender. Methods We retrospectively collected 320 patient records with four consecutive hourly scintigraphic measures of percent intragastric residual at the Kansas University Medical Center. We obtained parameter estimates with the Bayesian hierarchical models using informative priors from previous research. Key Results The PE or MPE model captured the time dependent GE rate better than the linear model. The estimated GE rates more than doubled for those without gastroparesis compared to patients diagnosed with gastroparesis. Males tended to empty gastric content faster but were not significantly different from females at the 5% level. Conclusions & Inferences The point estimates and 95% credible interval for GE rates obtained with the PE and MPE models may provide an alternative diagnostic tool for clinicians since it utilizes gastric emptying scintigraphy measures at multiple endpoints which may be sensitive to different aspects of the disease. No agreement in lag phases was obtained by the three models based on respective definitions from previous researches, but similar results would be obtained with the PE and MPE models if both defined lag phase by back projecting the regression lines to the same gastric retention level.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

Stress profile, coping style, anxiety, depression, and gastric emptying as predictors of functional dyspepsia: A case-control study

Objective

To determine whether gastric emptying, stomach peristaltic frequencies, stress profile, depressive symptoms, anxiety, and salivary cortisol levels could predict functional dyspepsia (FD).

Methods

Magnetogastrography (MGG) was used to measure gastric emptying time and the gastric peristaltic frequencies in 15 patients with FD diagnosis and in 17 healthy volunteers. In all the participants, stress profile, anxiety, and depressive symptoms were evaluated by means of standardized questionnaires, and morning salivary samples were collected for the measurement of cortisol levels. A univariate logistic regression model was used to examine the probability of the measured variables to predict the presence of FD.

Results

The univariate logistic regression model showed that the half-time of gastric emptying (OR=1.16 P=.01); the subscale of stress items (OR=1.08, P=.003); negative appraisal of subscale coping strategies (OR=1.03, P=0.007); anxiety (OR=1.05, P=.01); and depression (OR=1.23, P=.02) had a significant predictive value for the presence of FD. However, by applying the stricter multiple comparison criterions, only stress, negative appraisal, and anxiety arose as predictors of FD. The FD patients compared with healthy volunteers showed significantly elevated half-time of gastric empting (P<.0006), high scores in the subscales of stress (P<.000003), in behavior type “A” (P<.04), in coping styles (P<.008), in depression (P<.0004), and in anxiety (P<.0002).

Conclusions

These findings indicate that psychosocial stress, mood symptoms, and coping style are predictors of FD. The stress shows high sensibility and specificity in the patients with FD, indicating a contribution in the etiopathogenesis of dyspepsia.     

Effects of fenfluramine on food intake, body weight, gastric emptying and brain monoamines in syrian hamsters

In the first experiment, dose-inhibition and -time functions are documented for the anorectic effects of d,l-fenfluramine in Syrian hamsters (Mesocricetus auratus). A dose of 20 mg/kg (IP) inhibited feeding for at least 2-4 hr. In the second experiment, chronic treatment of hamsters housed either in running wheels (exercise) or standard (sedentary) conditions with d,l-fenfluramine (20 mg/kg) produced an attenuation of weight gain relative to vehicle-treated controls. However, there was no differential weight loss in the exercising drug-treated group. This result was also obtained using 10 mg/kg d-fenfluramine. In the third experiment, d,l-fenfluramine greatly inhibited gastric emptying of a test meal in hamsters. In the fourth experiment, hamsters were found to sustain only small and transient decreases in brain 5HT and 5HIAA levels after acute or chronic treatment with d,l-fenfluramine. These findings are compared and contrasted with the known effects of fenfluramine in rats. It is concluded that there may be species differences in the impact of fenfluramine on brain function, and that this may not be in any simple way related to the anorexigenic action of this drug.