GOALS:The goal of this study was to determine the effect and safety of domperidone on QTc interval at the commonly prescribed doses of 30 to 80 mg daily.
BACKGROUND:Domperidone is a dopamine receptor ...antagonist used for the treatment of gastroparesis. However, it has been associated with QT prolongation, ventricular arrhythmias, and sudden cardiac death.
STUDY:This study analyzed patients prescribed domperidone for treatment of gastroparesis between January 2012 and September 2017 at a single center. This study reviewed EKGs, primarily the QTc interval, taken at baseline, 2 to 6 months after initiation of domperidone, 6 to 12 months after initiation, and ≥12 months after initiation. Concurrent QTc prolonging medications were recorded for each patient. The primary endpoint was QTc prolongation >500 ms. Secondary endpoints were QTc >450 ms for males, a QTc>470 ms for females, QTc prolongation ≥20 ms above baseline, and QTc prolongation >60 ms above baseline.
RESULTS:In total, 246 patients were included for analysis (age, 46.3±17.4 y; F 209). EKGs were available for all 246 patients before treatment, 170 patients at 2 to 6 months, 135 at 6 to 12 months, and 152 patients at least 1 year after domperidone initiation.Of 246 subjects, 15 patients (6.1%, 9 female) had clinically important QTc prolongation; 11 had QTc >450 ms for males or >470 ms for females; none had QTc prolongation >500 ms; 5 (2.0%) had >60 ms over baseline and 61 (24.7%) patients had QTc increase of ≥20 ms but <60 ms from baseline.
CONCLUSIONS:Domperidone at the conventionally used doses to treat gastroparesis (30 to 80 mg/d) was associated with QTc prolongation in only 6% of patients with no QT interval reaching the point considered to be clinically significant. These data suggest that domperidone can be safely prescribed at doses of 30 to 80 mg daily for the treatment of gastroparesis.
Abstract Background Delayed gastric emptying (DGE) after pancreaticoduodenectomy increases length of hospital stay and costs, and may be influenced by surgical techniques. Methods We retrospectively ...compared 400 patients with antecolic gastrojejunostomy with 400 patients with retrocolic gastrojejunostomy for the occurrence of DGE. Results The prevalence of DGE was 15% in the antecolic group and 21% in the retrocolic group ( P = .021), and median length of stay was shorter for the former (8 vs 10 days, P = .001). The difference was statistically significant with grade A DGE (9% vs 14%, P = .038), but not B or C. In a multivariate analysis, DGE was influenced by retrocolic reconstruction, as well as older age, chronic pancreatitis, preoperative bilirubin level, a history of previous upper abdominal surgery, and postoperative pancreatic fistula. Conclusions An antecolic gastrojejunostomy for classic non–pylorus-preserving pancreaticoduodenectomy is associated with a lower incidence of mild DGE (grade A) and a shorter length of stay.
Background
The reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter‐individual reproducibility of these ...parameters in patients with upper gastrointestinal symptoms.
Methods
Sixty patients (21 diabetics, 39 non‐diabetics) with upper gastrointestinal symptoms underwent scintigraphic‐assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter‐individual coefficients of variation (COV) of GE endpoints were analyzed.
Results
The GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2. However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2, the inter‐individual coefficients of variation was 40%; the intra‐individual COV was 20%, comparable in diabetics and non‐diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%).
Conclusions & Inferences
Among patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.
Assessments of gastric emptying (GE) measured with scintigraphy are relatively reproducible in patients with upper gastrointestinal symptoms. In 30% of patients, the characterization of GE as normal, delayed, and rapid differed between the two studies.
Background & Aims Gastric electrical stimulation (GES) treats refractory gastroparesis by delivering electric current, via electrodes, to gastric smooth muscle. Enterra therapy (Medtronic, Inc, ...Minneapolis, MN) uses an implantable neurostimulator with a high-frequency, low-energy output. We performed a controlled, multicenter, prospective study to evaluate the safety and efficacy of Enterra therapy in patients with chronic intractable nausea and vomiting from diabetic gastroparesis (DGP). Methods Patients with refractory DGP (n = 55; mean age, 38 y; 66% female, 5.9 years of DGP) were given implants of the Enterra gastric stimulation system. After surgery, all patients had the stimulator turned on for 6 weeks and then they randomly were assigned to groups that had consecutive 3-month, cross-over periods with the device on or off. After this period, the device was turned on in all patients and they were followed up, unblinded, for 4.5 months. Results The median reduction in weekly vomiting frequency (WVF) at 6 weeks, compared with baseline, was 57% ( P < .001). There was no difference in WVF between patients who had the device turned on or off during the cross-over period (median reduction, 0%; P = .215). At 1 year, the WVF of all patients was significantly lower than baseline values (median reduction, 67.8%; P < .001). Patients also had significant improvements in total symptom score, gastric emptying, quality of life, and median days in the hospital. Conclusions In patients with intractable DGP, 6 weeks of GES therapy with Enterra significantly reduced vomiting and gastroparetic symptoms. Patients had improvements in subjective and objective parameters with chronic stimulation after 12 months of GES, compared with baseline.
The interstitial cells of Cajal (ICCs) are fundamental in the generation of gastric slow waves. The role of these cells in gastroparesis has not been established. We studied 14 gastroparetic patients ...(9 diabetic, 4 idiopathic, and 1 postsurgical) for whom standard medical therapy had failed and who had been treated with a gastric electrical stimulator for at least 3 months. All patients had a full-thickness antral gastric wall biopsy at the time of surgery. The biopsy samples were stained with c
-kit and scored for the presence of ICCs. Baseline electrogastrogram recordings were obtained for 30 minutes in the fasting state and for 2 hours after a test meal. The patients assessed their total symptom score at baseline and at 3 months. Five patients had almost no ICCs and were compared with nine patients with 20% to normal cell numbers. Both groups did respond symptomatically to gastric electrical stimulation. However, patients with depleted ICCs had significantly more tachygastria and had significantly greater total symptom scores at baseline and after 3 months of gastric electrical stimulation. ICCs are absent in some patients (up to a third) with diabetic or idiopathic gastroparesis, and the absence of these cells is associated with abnormalities of gastric slow waves, worse symptoms, and less improvement with gastric electrical stimulation.
Background
Gastroparesis is a gastrointestinal motility dysfunction characterized by delayed gastric emptying in the absence of gastric mechanical obstruction. Data on the epidemiology of ...gastroparesis are sparse even though the condition substantially impairs patients' quality of life. The aim of this study was to describe the epidemiology and estimate the short‐term healthcare resource use burden of gastroparesis in a large population.
Methods
This cross‐sectional study utilized computerized data from Maccabi Healthcare Services, a 2.5‐million member state‐mandated health organization in Israel. Data were collected between 2003 and 2018 to assess the prevalence of gastroparesis. Definite gastroparesis was defined by gastroparesis diagnosis and gastric emptying test. Probable gastroparesis was defined by gastroparesis diagnosis only. To compare the healthcare resource utilization (HCRU), data were also collected on controls that were individually matched (1:2) for age, sex, and comorbidities.
Key Results
A total of 522 patients with gastroparesis were identified (21.1 per 100,000 WHO age‐standardized), including 204 with definite gastroparesis (8.6 per 100,000 WHO). Male to female ratio was 1:2 and mean ± SD age of 54.7 ± 17.1 years. Diabetes accounted for 25.9% of gastroparesis cases and the rest were idiopathic. Gastroparesis patients were more likely to have cardiovascular diseases (10% vs. 6.9% for controls, p = 0.034) and lower prevalence of obesity (17% vs. 24.4%, p < 0.001). HCRU within the 2 years after index date were higher with more hospitalizations than controls (26.4% vs. 15.4%, p < 0.001), and more emergency room visits (31.6% vs. 24.1%, p = 0.002).
Conclusions & Inferences
Gastroparesis is uncommon or under‐documented in community care settings. Gastroparesis in general is associated with cardiovascular morbidities, lower BMI, and elevated utilization of healthcare services.
The aim of this study was to describe the epidemiology and estimate the short‐term healthcare resource use and burden of gastroparesis in a large population: Gastroparesis is uncommon or under‐documented in community care settings. Gastroparesis in general is associated with cardiovascular morbidities, lower BMI, and elevated utilization of healthcare services.
The medical literature states that solid gastric-emptying studies are more sensitive for the detection of gastroparesis than are liquid studies; thus, liquid studies are rarely required. However, we ...have seen patients with normal solid but delayed liquid emptying. The purpose of this investigation was to determine whether a study of clear liquid gastric emptying has added value for the diagnosis of gastroparesis over a study of solid emptying alone.
A total of 101 patients underwent both solid and liquid gastric-emptying studies, acquired sequentially on the same day. A 30-min (1-min frames) liquid study (300 mL of water with 7.4 MBq 0.2 mCi of (111)In-diethylenetriaminepentaacetic acid) was followed by a standardized 4-h solid-meal study (a (99m)Tc-sulfur colloid-labeled egg-substitute sandwich meal). Emptying was quantified as a best-fit exponential emptying rate (T1/2) for liquids and percentage emptying at 4 h for solid emptying. Thirty healthy volunteers underwent a study of clear liquid emptying to establish normal values. The results of the liquid and solid studies were compared. (111)In liquid downscatter into the subsequent (99m)Tc solid meal results was analyzed.
The upper range of normal for clear liquid emptying (T1/2) for healthy volunteers was 22 min (mean +/- 3 SDs) and 19 min (mean +/- 2 SDs). Of 101 patients, delayed emptying was found in 36% of liquid and 16% of solid studies. Of all patients with normal solid emptying, 32% had delayed liquid emptying. (111)In downscatter into the (99m)Tc window was not generally significant.
For the detection of gastroparesis, a 30-min study of clear liquid gastric-emptying has considerable added diagnostic value over a study of solid emptying alone.
Recent data from the Diabetes Control and Complications Trial/Epidemiology of Diabetic Interventions and Complications cohort indicate that the disease burden of gastroparesis in diabetes remains ...high, consistent with the outcome of cross-sectional studies in type 1 and 2 diabetes. An improved understanding of the pathogenesis of diabetic gastroparesis at the cellular level has emerged in the last decade, particularly as a result of initiatives such as the National Institute of Health funded Gastroparesis Clinical Research Consortium in the US. Management of diabetic gastroparesis involves dietary and psychological support, attention to glycaemic control, and the use of prokinetic agents. Given that the relationship between upper gastrointestinal symptoms and the rate of gastric emptying is weak, therapies targeted specifically at symptoms, such as nausea or pain, are important. The relationship between gastric emptying and postprandial glycaemia is complex and inter-dependent. Short-acting glucagon-like peptide-1 agonists, that slow gastric emptying, can be used to reduce postprandial glycaemic excursions and, in combination with basal insulin, result in substantial reductions in glycated haemoglobin in type 2 patients.
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