Authors: Neha R. Santucci (1Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA), Joshua Corsiglia (1Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA), Khalil EI-Chammas (1Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA), Oleksandr Shumeiko (3Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA), Chunyan Liu (4Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA), Ajay Kaul (1Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA; 2Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA)
Categories: Article, dyspepsia, gastric scintigraphy, gastroparesis, liquid gastric emptying, pediatrics, solid gastric emptying
Source: Neurogastroenterology and motility
Doi: 10.1111/nmo.14701
Authors: Neha R. Santucci, Joshua Corsiglia, Khalil EI-Chammas, Oleksandr Shumeiko, Chunyan Liu, Ajay Kaul
There is limited data on gastric emptying in dyspeptic children. We aimed to determine solid and liquid emptying rates in dyspeptic children and correlate with clinical characteristics.
Charts of dyspeptic children undergoing 4-hour dual-phase gastric scintigraphy were reviewed for demographics, symptoms, and comorbidities.
In 1078 dyspeptic patients (65% females, median age 13years) vomiting (55%), nausea (53%), and abdominal pain (52%) were the most common symptoms. The most common comorbidities were mental health (32%), neurologic (27%), and hypermobility spectrum disorders (20%). Solid and liquid emptying rates were aligned in 61.23%. Delayed solid with normal liquid emptying were noted in 2.5%, compared to delayed liquid with normal solid emptying in 26.16%. Abdominal pain had a trend for association with delayed or normal solid emptying (p=0.06). Nausea was mostly reported with normal solid emptying (p<0.0001) and underreported in patients <12 years with vomiting (29%). Abnormal solid emptying (rapid and delayed) was noted more frequently in children with mental health disorders (p=0.027). Rapid liquid emptying was more common in children with genetic disorders (p=0.032).
Over half of children with dyspepsia had delayed liquid gastric emptying, and one quarter had delayed liquid with normal solid emptying. Dual-phase gastric emptying studies may help target therapy in dyspeptic children. Nausea is not a reliable symptom for dyspepsia in younger children. Given the significant association of abnormal gastric emptying in children with mental health disorders, we recommend screening and treating children with dyspepsia.
Dyspepsia is a common condition in adults and children, and symptoms include nausea, vomiting, abdominal pain, poor appetite, early satiety, and weight loss.^1,2^ Symptoms of dyspepsia can be present with or without delayed gastric emptying.^3,4^ The most common symptoms associated with delayed gastric emptying in adults are nausea (74%), followed by vomiting (53%), and abdominal pain (45%).^5,6^ However, abdominal pain is the most frequently reported symptom in older children and adolescents while infants and younger children usually present with vomiting.^1,2,7^
Radionuclide scintigraphy is the gold standard for evaluation of gastric emptying.^8^ Gastric emptying of a solid meal through scintigraphy is usually recommended for testing gastric emptying despite different mechanisms for solid and liquid food emptying.^9^ The consensus recommendations for gastric emptying scintigraphy by the American Neurogastroenterology and Motility Society combined with the Society of Nuclear Medicine established normative emptying values after a standardized solid meal, which include gastric retention of >90% at 1 h, >60% at 2 h, and 10% at 4 h. ^8^ Some studies have shown significant variability of gastric emptying depending on age, volume, and route of emptying.^10,11^ Passage of >80% of the meal at 3 h was proposed as cutoff of normal liquid gastric emptying in infants and children <5years old.^10^ Similarly, in other studies, younger children had difficulty in completing a full meal, and a 4-hour protocol was used to evaluate gastric emptying^11^ Though these norms have not been validated in children, prior studies have not found differences in gastric emptying between different age groups, including both radionuclide scintigraphy and octanoid breath test.^12,13^
Delayed gastric emptying of liquids has been described in 13%-37% of dyspeptic adults, but the clinical significance remains unknown.^14,15^ Some studies suggest that liquid gastric emptying provides unreliable information.^9^ One study showed altered ghrelin physiology in children with functional dyspepsia-postprandial distress syndrome during liquid meal gastric emptying study using octanoid test.^16^ Another study showed no significant difference of gastric emptying between children with gastroesophageal reflux and healthy children with wide range of gastric emptying using 99Tc-DTPA-marked milk.^17^ There is limited data on gastric emptying of solids and liquids following a dual-phase test meal in dyspeptic children. Thus, the aims of this study were (a) determine the rates of solid and liquid gastric emptying in children with dyspepsia, (b) correlate solid and liquid gastric emptying with clinical characteristics, and (c) determine if nausea was a reliable symptom in children presenting with other symptoms of dyspepsia.
After obtaining institutional review board approval (IRB# 2020-0627), we retrospectively reviewed charts of children and young adults ages 1–21 with dyspepsia who underwent a standardized dual-phase scintigraphic gastric emptying study at our institution between January 2015 and December 2019. Data on demographics, symptoms (abdominal pain, nausea, vomiting, decreased appetite, including early satiety and fullness, and weight loss) as well as comorbidities was extracted from the medical records. Patients with ICD-10 diagnoses of organic GI disorders such as celiac disease, eosinophilic esophagitis, and inflammatory bowel disease; systemic conditions such as diabetes; those with transient or intermittent dyspeptic symptoms as well as those with incomplete gastric emptying scans due to vomiting, were excluded. Our institution utilizes the following standardized for the solid phase, 99mTc Sulfur Colloid mixed with a standard dose of 0.200 mCi (range of 0.100–0.300mCi)^13^; for the liquid phase, we used 67-Ga citrate with a standard dose of 0.085 mCi (range of 0.40–0.120 mCi). These are mixed with 4oz of eggbeaters (gold standard technetium binder) for the solid and 4oz of apple juice or water for the liquid phase to provide a 255 kcal meal.^18^ If the patients are on medications that affect gastric emptying, these are held for 3–5 days prior to the GES.^19^ Patient meal and length of time to eat are recorded. A two-minute image was taken every hour for 2 h (liquid) or 4 h (solid), or until solids reached 90% emptying. Normal liquid gastric emptying was defined as 40%–78% at 1 h and ≥ 78% at 2 h.^13^ Normal solid gastric emptying was defined as 10%–70% at 1 h, 40%–90% at 2 h, and ≥90% at 4 h. Patients were divided into three normal, delayed, or rapid emptying each for liquids and solids.
The characteristics of the study cohort were summarized by gastric scintigraphy phase (solid vs. liquid) and emptying speed groups (normal, delayed, or rapid). Frequency and percentages were reported for categorical variables while continuous variables were reported as mean, standard deviation, median, quartiles, min, and max values. Kruskal-Wallis test was used for comparing continuous variables between groups. Chi-square test or Fisher’s exact test (when more than 20% of the table cells have expected frequencies less than 5) was performed for associations between the categorical variables and the group variable. The agreement between solid and liquid emptying speeds was accessed using Kappa coefficient and symmetry test, which is a generalization of McNemar’s test. To assess reliability of the reported nausea in the subcohort of patients who had vomiting aged 3–21, detailed distribution of nausea by age was presented. Analyses were performed using SAS version 9.4 (SAS Institute Inc.) and R statistical software (R Foundation for Statistical Computing). A p value of <0.05 was considered significant.
A total of 1078 dyspetic patients were studied after excluding 54 patients with diabetes, celiac, and inflammatory bowel disease and 34 patients with emesis during the test, refusal, or an incomplete study (Figure 1). Of the 1078 patients studied, 65% were female, age ranged from 1 to 21 years, and median age was 14years (IQR 10.0, 16.0). Gastric emptying rates did not differ based on age (p=0.7). Vomiting, nausea, and abdominal pain were the most commonly reported symptoms (55%, 53%, and 52%, respectively) while decreased appetite and weight loss were reported less frequently (21.5% and 21.6%, respectively).
Figure 2 summarizes the percentages of patients with nausea in the subset of patients who had vomiting. Among the 587 patients between 3 and 21 years of age who had vomiting, 67/223 were 12years or younger and reported nausea (30% overall, range 9%–44% at each year of age) in comparison with 224/364 who were older than 12years and reported nausea (62% overall, range from 48% to 71% at each year of age). The most common comorbidities included mental health, neurologic, and hypermobility spectrum disorders (32%, 27%, and 20%, respectively). These were followed by genetic disorders, pulmonary disorders and disorders of the brain and gut (DBGI, 8.7%, 8.2%, and 4.5%, respectively).
Delayed liquid gastric emptying alone was noted in 53% patients with dyspepsia; 5% had rapid liquid emptying while 42% had normal liquid emptying (Table 1). Females were observed to be more in the delayed or rapid liquid emptying group than normal (69.9% and 64.8% vs. 58.7%, respectively, p=0.001). Males were noted more in the normal liquid emptying group than delayed or rapid (41.3% vs. 30.1% and 35.2%, respectively). In other words, females demonstrated more delayed liquid emptying than males (57% vs. 46%) and less normal liquid emptying (38% vs. 49%). None of the symptoms differed with rate of liquid emptying. Comorbid conditions did not differ except in those with genetic disorders, which were significantly more associated with rapid than normal or delayed group (p=0.032).
Delayed solid gastric emptying alone was noted in 29.3% patients with dyspepsia; 12.3% had rapid emptying; and 58.4% had normal solid emptying (Table 2). Females demonstrated more delayed solid emptying than males (32% vs. 24%, p=0.004). Nausea was more often reported with normal solid emptying than delayed or rapid solid emptying (p<0.0001; Figure 3). No other symptoms differed with the rate of solid emptying. Mental health disorders were more frequently noted with rapid or delayed than normal emptying for solids (p=0.027). Other comorbid conditions did not significantly differ between the groups. Table 3 outlines liquid and solid emptying characteristics for patients with relevant comorbidities such as mental health disorders and disorders of gut-brain interaction.
Rates of solid and liquid emptying were concordant (normal, delayed, and rapid) in 61.23% (Table 4). When different, delayed liquid emptying was more often accompanied by normal solid emptying than vice versa (26.16% vs. 2.5%, p<0.0001). Similarly, fewer patients with normal solid emptying had rapid liquid emptying than vice versa (1.39% vs. 8.44%, p<0.0001).
Literature on gastric emptying in children with dyspepsia is limited; there is a general paucity of incidence, prevalence rates, and norms for gastric emptying in pediatrics, as well as their correlation with symptoms. Multiple pathophysiologic mechanisms have been suggested for dyspepsia.^1,5^ However, treatments targeting them have been limited in number with suboptimal outcomes^7,20^ due to a general lack of understanding of symptomatology and available investigations. For example, delayed liquid gastric emptying has been reported in adults with symptoms of gastroparesis.^16^ However, its clinical significance is unclear. With this in mind, we attempted to characterize both solid and liquid gastric emptying in symptomatic children in addition to the more commonly employed solid gastric emptying alone. We assessed normal, delayed, and rapid gastric emptying rates in this cohort and established clinical correlation of symptoms with scintigraphic findings. This is the largest cohort reporting gastric emptying rates of solids and liquids and their correlation with symptoms in children with dyspepsia.
The rates of vomiting, nausea, and abdominal pain in our cohort of children with dyspepsia are similar to those reported in prior published pediatric studies.^1,5^ This is in contrast with adult studies, where abdominal pain was less commonly reported compared to nausea and vomiting.^6^ A recent study reported nausea to be the only correlated symptom in children ages 6–17 with delayed gastric emptying tying diagnosed by the spirulina breath test.^21^ However, we found that patients greater than 12years of age with vomiting seemed to report nausea at a relatively steady rate (62%, range 48%–71% at each year of age) compared with patients 12years of age or younger (29%, range 9%–44% at each year of age). This is consistent with prior studies reporting vomiting, not nausea, as the only predominant symptom in infants and younger children.^1,2,7^ Thus, vomiting may be a more reliable symptom reflecting dyspepsia in children younger than 12years of age in comparison with nausea. Younger children may be unable to express nausea as a symptom and may instead report abdominal pain as a surrogate for nausea. This is an important observation to consider when developing screening questionnaires for dyspepsia in children.
Similar to adults^15^ (37%), 30% of dyspeptic children had normal gastric emptying in our cohort. This reinforces the fact that a normal gastric emptying scan does not preclude severity of symptoms in dyspeptic children, which are equally important for treatment considerations as are emptying rates. In our cohort with dyspesia, delayed liquid gastric emptying was more common than delayed solid gastric emptying (53% vs. 29% respectively). Thus, more than half the dyspeptic children had delayed liquid gastric emptying, and one quarter had delayed liquid emptying in the presence of normal solid gastric emptying. Prior studies in symptomatic adults have reported up to 13% delayed liquid emptying in the presence of normal solid gastric emptying.^15^ Thus, delayed liquid emptying with normal solid emptying appears to be a more common finding in dyspeptic children than adults. Consequently, this important finding may be missed in evaluating and treating dyspepsia in children if only solid gastric emptying is tested (as recommended by the adult gastroparesis consortium). Liquids empty exponentially from the stomach without a lag phase as compared with solids. However, the fundus relaxes to accommodate liquids when they enter the stomach. Disruptions in fundal accommodation could explain abnormalities in liquid gastric emptying.^22^ This mechanism may be more predominant in children than adults and may explain the reported efficacy of medications like cyproheptadine, mirtazapine, and buspirone in improving symptoms of abnormal gastric emptying in children by their effect on fundal accommodation.^23–27^
In both solid and liquid emptying groups, females had more delayed gastric emptying than males. This is similar to studies in adults^6,28^ but expands from smaller pediatric studies where the ratios have varied according to age groups.^2^ The larger sample size in our cohort probably contributed to similar findings to those reported in adults. Studies have suggested that the standard values should be modified to account for gender differences.^29^ Unlike our study, it revealed that the prevalence of delayed gastric emptying in patients with functional dyspepsia is not significantly different between men and women.^29^ Hormonal effects on motility have been suggested as a plausible pathophysiologic mechanism to explain this difference between the genders.^30,31^ These gender-specific differences highlight the need to consider gender-related mechanisms when evaluating and managing gastric motility disorders in pediatric populations.
In the analysis of symptom correlation with gastric emptying rates, abdominal pain was more commonly reported with delayed gastric emptying for both the solid and liquid phase emptying. In addition, nausea was more commonly associated with normal solid gastric emptying, again emphasizing the lack of correlation of symptoms with gastric emptying rates in children. Overall, there was no difference in the distribution of symptoms between liquid and solid emptying. This further underscores the need to assess liquid gastric emptying in children with dyspepsia.
Rapid gastric emptying has been associated with symptoms of dumping.^32,33^ We found 12% of patients with rapid gastric emptying of solids in our cohort. While they had associated abdominal pain, decreased appetite, nausea, vomiting, and weight loss (some of which are symptoms of early dumping syndrome), these were not more common than in normal or delayed emptying groups. Rapid emptying of solids has been reported in the past.^30^ However, in our cohort, we reported a small percentage of dyspeptic patients (5%) with rapid liquid emptying.
Regarding the association of comorbidities with gastric emptying rates for solids and liquids, mental health disorders such as anxiety and depression were the most common, reported in approximately a third of the population (32%). This confirms similar findings in prior studies reporting a prevalence of 28%.^2,5^ Mental health disorders were associated more with an abnormal solid gastric emptying (delayed and rapid). This underscores the impact of psychological factors that can be associated with disordered gastric motility. Thus, screening and treatment of these conditions need to be taken into consideration while managing patients with dyspepsia. Treatments such as cognitive behavioral therapy and hypnotherapy that benefit anxiety and depression may also improve gastric emptying and/or symptoms of abnormal gastric emptying^34,35^ Neurologic and hypermobility spectrum disorders have been previously reported to occur in association with gastroparesis,^1,36–38^ but we did not find a significant association of these conditions with delayed gastric emptying in our study.
While a large sample size was a strength of our study, it was however, limited by the retrospective design. It is challenging to carry out large-scale prospective studies in the pediatric population due to significant ethical and logistical issues. The retrospective nature prevented determination of symptom severity and duration, including use of patient-reported outcome measures and questionnaires, episodic symptoms, differentiation between functional dyspepsia subtypes, detailed investigations performed, prescribed medication, or illicit substance use. Patients ages 1–21 were included in the study, and broad variability might contribute to wide range of gastric emptying study results. Nonetheless, we were able to accomplish a thorough analysis of solid and liquid gastric emptying as well as symptom correlation with the rate of gastric emptying in pediatric patients due to our large sample size.
Potential avenues for future research may include evaluation of changes with medication use and the differentiation between epigastric pain and postprandial distress subtypes.
In conclusion, our data shows no association between dyspepsia symptoms and gastric emptying rates in children. We report delayed liquid emptying to be more prevalent in children with dyspepsia and therefore propose performing dual-phase gastric emptying studies to provide a better insight into the pathophysiology and help target therapy. We also recommend screening children with dyspepsia for mental health disorders in view of the significant overlap of these conditions.