At 48-weeks, 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis
In a subset of patients, full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls.
The 48-week clinical outcomes were similar. Symptom severity remained “on average unchanged despite the change in gastric-emptying status”
My take (borrowed from authors): This study shows that “patients initially classified as one or the other are not distinguishable by clinical features or by follow-up assessment of gastric emptying…both disorders are unified by characteristic pathologic features, best summarized as a macrophage-driven “cajalopathy” of the stomach.”
While the authors state that a GES lacks reliability, the associated editorial argues that a GES may still be useful (J Tan et al. pg 1931. Full text: Gastroparesis: A Dead-end Street After All?) As individuals with delayed GE “fail to benefiit” from neuromodulators, a GES may influence treatment. However, they note that ACG guidelines indicate that a GES is not needed and all patients with dyspepsia symptoms can be treated in a “uniform sequence of proton pump inhibitors, tricyclic antidepressants and prokinetics as third-line therapy.”
This article provides insight into the topic of gastric emptying with a focus on patients with diabetes. A few key points:
Gastric emptying affects glucose homeostasis in patients with diabetes; delayed gastric emptying in patients with type 2 diabetes could have beneficial effects in this regard.
Delayed gastric emptying occurs in 40-47% of adults with diabetes; rapid emptying occurs in 20-22%.
Upper GI symptoms do NOT correlate with gastric emptying. Prevalence of these symptoms is highest in those with normal gastric emptying (43-52% in those with normal emptying compared with 19-28% with delayed emptying, and 20-37% with rapid emptying)
“Functional dyspepsia-like symptoms in gastroparesis may arise not through motility changes but rather through the parallel effects of oxidative stress and inflammation on nocireceptors and on other afferents that produce the symptoms.”
My take: Knowing how quickly the stomach empties rarely helps management. In this review, Dr. Goyal states that “the effective treatment of symptoms in diabetic gastroparesis may be similar to the treatment of functional dyspepsia.”
Also, noted in same issue of NEJM:
TB Corcoran et al.NEJM 2021; 384: 1731-1741. Dexamethasone and Surgical-Site InfectionKey finding: A single dose of dexamathosone (8 mg) did not increase the risk of surgical site infection; this is in contrast to long-term glucocorticoid therapy which is a risk factor for infection and wound dehiscence.
J Salwa et al. NEJM 2021; 384: 1684-6. Designing an Independent Public Health Agency. This article makes compelling arguments for separating health agencies from political influence. The FDA, the CDC, and HHS in the previous administration were pressured and undermined. In contrast, the Federal Reserve Board, which has 14 year terms that require ‘removal only for cause,’ was “reliably [able to] exert federal power because of its institutional features as an independent agency.”
A recent yard sign from my wife for neighborhood walkers during the pandemic
P Ducrotte el al (Gastroenterol 2020; 158: 506-14, editorial 461-3) examined the use of an implanted gastric electrical stimulation (GES) in 172 patients in a randomized crossover trial (mean age 45 years). GES device was implanted and left unactivated until patients were randomized in a double-blind manner to receive stimulation (for 4 months) or not. Patients had vomiting that was either idiopathic, postsurgical or associated with diabetic gastroparesis (n=72).
A significant decrease in vomiting occurred with the device on based on a nonvalidated vomiting score. During the ON period, vomiting was improved with score of 2.2 compared to vomiting score of 1.8 with device off. 30.6% of patients reported at least a 1 point improvement with device ON compared to device OFF. However, 16.5% of patients reported improvement with device OFF compared to device ON.
Gastric emptying was not accelerated during treatment (device on) compared to no treatment
GES was NOT associated with increased quality of life
GES was not associated with improved nutritional parameters
Adverse effects included pain (n=26) or infection (n=16) at the insertion site of GES; 3 patients required GES removal.
My take (from editorial): “Taking into account the modest magnitude of therapeutic benefit, the cost of the treatment and the potential for adverse events with GES, it seems advisable to exhaust all (symptomatic) therapeutic options” beforehand.
COVID-19 March 2020: MMWR Report (Link to report from Bryan Vartabedian 33mail)
March 1-28 2020, 84% of hospitalized U.S. patients had underlying diseases -he most common being obesity, hypertension, chronic lung disease, diabetes mellitus, and cardiovascular disease.
Hospitalization rates increased with age, with a rate of 0.3 (per 100,000) in persons aged 0–4 years, 0.1 in those aged 5–17 years, 2.5 in those aged 18–49 years, 7.4 in those aged 50–64 years, and 13.8 in those aged ≥65 years
Perhaps Socrates was a gastroenterologist. So much of what we think we know, we are finding out is poorly understood. This applies to gallbladder dyskinesia, sphincter of Oddi dysfunction and now gastroparesis.
A recent study (PJ Pasricha et al. Gastroenterol 2015; 149: 1762-74, commentary 1666-68) and commentary show how little we understand about gastroparesis.
The study was a large prospective surgery of 262 adult patients with gastroparesis (either diabetic or idiopathic).
28% had improvement in the gastroparesis cardinal symptom index (GCSI) at 48 weeks. Beyond 48 weeks, there were no significant reductions through week 192.
Favorable characteristics: male gender, age 50 and older, initial infectious prodrome (18% of cohort), antidepressant usage, and 4-hour gastric retention greater than 20%.
Unfavorable characteristics: obesity, smoking, use of pain modulators, moderate to severe abdominal pain, severe reflux, and moderate to severe depression.
The commentary suggests that those with the higher GCSI improved, in part, because of a regression toward the mean bias. Other important commentary:
“More severely delayed gastric emptying was associated with a greater likelihood of improvement”
“There was no differences in outcome between diabetic or idiopathic gastroparesis.”
Gastric emptying tests are not reliable: “Pathophysiologic tests are useful in clinical practice if they are reproducible, explain the symptoms, guide therapeutic choices, and determine response to therapy and long-term prognosis. Despite its popularity, the gastric emptying test scores low on most of these criteria.”
“A metaanalysis found no correlation between the change in gastric emptying rate and the symptom response during prokinetic therapy…A 5-year prospective follow-up study of …functional dyspepsia…found that more than 50% improved…with no relation to the presence of delayed gastric emptying.”
“Using the term gastroparesis also can lead to premature closure in our efforts to understand the pathophysiology of symptoms…can lead to botulinum injections into the pylorus or placement of gastric stimulators (formerly called gastric pacemakers) for gastroparesis, both of which have been shown to be nonefficacious in controlled trials.”
My take: It is unclear “when to consider gastric emptying testing and how to use it in patient management.” For the pediatric population, gastroparesis is more likely to be associated with a prodromal infection which increases the likelihood of recovery.
A recent theme on this blog has been the difficulty of studying inexpensive therapies. The issue is that there are not strong incentives for pharmaceutical companies to invest in treatment trials when the potential for profits is meager. Fortunately, there are other funding mechanisms. A recent study (NJ Talley et al. Gastroenterol 2015; 149:340-9), sponsored by the NIH, still was challenging. One of the reasons is that when medicines are already approved by the FDA that can be used off-label and this can undermine recruitment.
Due to difficulty with enrollment, the researchers of this current study expanded to a total of 8 sites (initially 5) and settled for 292 patients rather than their goal of 400. After a baseline washout of 2- to 4-week with assessment, patients with Rome II criteria for functional dyspepsia (FD) were assigned in a randomized, double-blind trial to either placebo, amitriptyline 50 mg, or escitalopram 10 mg for 10 weeks.
History of depression and not using antidepressants.
Symptom resolution with antisecretory therapy (eg. proton pump inhibitors)
History of esophagitis, ulcers, or organic gastrointestinal disease
Major physical illness
Nonsteroidal anti-inflammatory drugs
Required: previous normal EGD within 5 years
“ulcer-like dyspepsia” pain centered in the upper abdomen is the predominant symptom
“dysmotility-like dyspepsia” non pain symptom predominates: fullness, bloating, early satiety, and nausea
Adequate relief was noted in 40% of placebo-treated, 53% of amitriptyline-treated, and 38% of escitalopram-treated patients
Ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief compared with placebo for odds ratio of 3.1
Delayed gastric emptying was associated with being less likely to report adequate relief with an odds ratio of 0.4
Safety: while adverse effects were common, “there was no overall difference between the 3 arms (except in neurologic symptoms, with highest rates in the escitalopram arm) suggesting that…TCAs will be generally well tolerated at low doses.”
The associated editorial (pages 270-2) notes that the overall benefits of amitriptyline were modest. They also reviewed the NORIG study (JAMA 2013; 310: 2640-9) which examined nortriptyline and placebo for idiopathic gastroparesis (n=130). Similar to this study from Talley et al, the NORIG study found a lack of response to tricyclic antidepressants in this cohort with delayed gastric emptying and dysmotility; “the lack of efficacy in patients with dyspepsia with delayed gastric emptying suggests the possible utility of scintigrahic testing to select patients” for amitriptyline therapy.
Bottomline: This well-designed study supports the use of amitriptyline, but not escitalopram for the use of FD, mainly in those with pain-predominant symptoms.
Over 24 months, 60% had significant improvement regardless of treatment
The second study by Rodriguez et al is titled “Clinical Presentation, Response to Therapy, and Outcome of Gastroparesis in Children.”
Restrospective study with 230 children, mean age 9 years. In adolescents, female gender was more common (77%) whereas in infants (n=36), male gender was more common (61%). Most common causes were postviral in 42%, mitochondrial in 18%, and diabetes in 5%.
Delayed gastric emptying was defined as having solids or liquids emptying <40% of the meal at one hour.
Resolution occurred in 22% at 6 months, 53% at 18 months, and 61% at 36 months. Median time to resolution was 14 months; though among resolvers, 84% did so by 12 months.
Presence of longer duration of symptoms and mitochondrial disorder was associated with lower rates of resolution.
Younger age and response to promotility agents increased likelihood of resolution
Treatment with proton pump inhibitors (PPIs) were used in 79% as first-line agents; only 3% reported resolution of symptoms with PPIs.
Prokinetics: Domperidone (0.1-0.2mg/kg/dose qid to max of 10mg) in 33 patients. Tegaserod in 20 patients. Metoclopropramide in 142 patients. Erythromycin (EES) in 40 patients (3-10 mg/kg/dose qid). Of these agents, metoclopropramide was inferior with an 80% failure rate. In contrast, EES was associated with symptom resolution in 5% and symptom improvement in 46%. Domperidone was associated with symptom resolution in 26% and symptom improvement in 48%.
The third study by Bhardwaj et al highlights “Impaired Gastric Emptying and Small Bowel Transit in Children with Mitochondrial Disorders.”
Prospective study enrolled 26 subjects from mitochondrial clinic. 58 patients were screened but the majority were not eligible; the most common reasons included the following: 14 were receiving enteral feedings, 1 was receiving parenteral nutrition, 6 had no GI symptoms.
Delayed gastric emptying was considered if >50% at 90 minutes of a solid meal was present, at 60 minutes for semisolid, and at 40 minutes for liquid meal. For small bowel transit, delayed transit was considered if radiotracer had not reached cecum within 4 hours. Severely prolonged transit was diagnosed if transit time exceeded 6 hours.
In this cohort, 18 (69%) had delayed gastric emptying and 12 (46%) had prolonged small bowel transit. Common symptoms included abdominal pain and vomiting.
In the small numbers of patients who received prokinetics,there was a poor response. One of three patients with bethanecol and two of five patients with metoclopropramide had normalized GE time; one patient treated with azithromycin continued with abnormal GE time
-Gastroenterol 2011; 140: 101. Clinical features -mostly females, often incr BMI. Defined as severe gastroparesis if >35% at 4hrs, moderate if 20-35%, and mild if <20%.
-Clincal Gastro & Hep 2011; 9: 5. Review of diabetic gastroparesis & mgt.
-Clin Gastro & Hep 2009; 7: 823. Radiation from gastric emptying is ~10mrad, CXR is 12mrad, yearly background is 300mrad.
1 hr 37-90%
2 hr 30-60%
4 hr 0-10%
-Gastroenterol 2009; 136: 1526. Tests of gastric emptying -review.
-Clin Gastro & Hep 2008; 6: 1309. algorithm for nausea & delayed GE. REC;
1. small meals, low fiber/fat
2. prokinetic: reglan, EES, ?domperidone
3. Antiemetics: zofran, prochloroperazine
5. ?Botox injection
6. jejunal feeds