Gastric and Small Bowel Motility: Gastric and Small Bowel Motility: Slow Emptying

0:00Welcome to Board Pearls. This is episode one of two of the Gastric and Small Bowel Motility chapter, in the Stomach and Small Bowel Disorders module. This episode is gastroparesis. A man with diabetes and vomiting carries it. His case shows what the stomach needs to empty and which of those his diabetes has broken, what else on his medication list is slowing his stomach, why his symptoms can't make the diagnosis, which test comes first and how the emptying study must be done to mean anything, and how treatment steps up from diet and drug review through prokinetics to procedures. A woman on semaglutide shows the most common testing pitfall today. The rest of the chapter covers cyclic vomiting and cannabis hyperemesis, intestinal pseudo-obstruction, and functional dyspepsia.

0:45Here's the patient. A forty-one-year-old man has had type one diabetes for twenty-four years, with a hemoglobin A1c of nine point eight, retinopathy, and numb feet. For eight months he's had nausea, fullness after a few bites, bloating, and vomiting of food he ate the day before. He's lost fifteen pounds. He takes insulin, gabapentin, and, recently, oxycodone for foot pain. He smokes cannabis most evenings to help his nausea.

1:14His story suggests gastroparesis, objectively delayed gastric emptying without a mechanical obstruction. It's only suspected so far, and proving it comes later. But first it helps to see why he might have it, because every cause of gastroparesis breaks one of three things the stomach needs to empty.

1:31The upper stomach is a reservoir. When food arrives, vagal signals using nitric oxide and vasoactive intestinal peptide relax it, which is called accommodation, so the meal is stored without pressure building up. The lower stomach is a pump. The antrum grinds solids into particles of a millimeter or two and pushes them through the pylorus in coordinated contractions. And the pump is paced by the interstitial cells of Cajal, along the greater curvature, which fire an electrical slow wave three times a minute that sets the rhythm and direction of the contractions.

2:03So emptying needs an intact vagus, intact interstitial cells, and working smooth muscle. Lose any one, and the stomach empties slowly. Every cause fits one of those three, and they all end in the same symptoms, whichever fails first.

2:18His diabetes has damaged two of the three. Long-standing high glucose causes autonomic neuropathy that injures the vagus, blunting accommodation and disrupting the coordination of the antrum and duodenum. It also depletes the interstitial cells of Cajal, with oxidative stress from macrophages increasingly seen as the driver.

2:37Diabetes is the most common identifiable cause, and two related facts shape his testing. Up to half of people with moderately controlled diabetes have delayed emptying on testing, many without symptoms. And acute hyperglycemia slows emptying by itself, so a glucose over two hundred during a test can produce a false result. That's why glucose control is part of both the diagnosis and the treatment.

3:02The other causes follow the same logic. Idiopathic gastroparesis is the other large group and a diagnosis of exclusion, classically a young or middle-aged woman. A subset is post-infectious, beginning weeks to months after a gastroenteritis. A history of norovirus, Epstein-Barr virus, cytomegalovirus, or herpesvirus points there rather than to a deeper neurologic or cancer workup.

3:29Surgery is a cause that's easy to miss unless it's asked about. Any operation that injures the vagus or distorts the antrum can cause it: fundoplication, sleeve gastrectomy, though reflux is the commoner problem after a sleeve, esophagectomy, and the prototype, truncal vagotomy without a drainage procedure. So any upper GI or chest surgery is asked about directly.

3:52The remaining secondary causes are systemic diseases. Parkinson disease causes it through enteric and vagal dysfunction, often before the motor diagnosis. Scleroderma causes nerve and then muscle failure, with up to eighty percent of patients having measurable upper gut dysmotility. Amyloidosis, light chain or transthyretin, infiltrates the wall. Hypothyroidism slows the smooth muscle and is screened in every new workup. And small cell lung cancer with anti-Hu antibodies is the prototype paraneoplastic cause.

4:24His medication list matters just as much, because drugs are the most common fixable cause. Opioids slow transit at every level by acting on mu receptors in the gut's nerves. Anticholinergics, including tricyclics, antihistamines, antiparkinsonian drugs, and phenothiazines, inhibit antral contractions. Chronic tetrahydrocannabinol, THC, slows emptying through cannabinoid type one, CB1, receptors. Cannabidiol can improve symptoms even as it slows emptying further, another sign that emptying and symptoms track poorly.

5:00One drug class now dominates the problem. Glucagon-like peptide one, GLP-1, receptor agonists, semaglutide, liraglutide, tirzepatide, and dulaglutide, slow antral contractions and act on central satiety signaling. They delay emptying in people whose stomachs are otherwise normal. Stopping the drug often resolves the symptoms and normalizes the study.

5:23His own list has three of those slowing effects. Oxycodone slows his stomach. His evening cannabis does too. And an A1c of nine point eight percent means he's often hyperglycemic, which slows it further. So he has his diabetes plus three things that can be changed.

5:40None of that makes the diagnosis, and neither do his symptoms. Nausea, vomiting, early satiety, fullness, bloating, and upper abdominal pain also occur in functional dyspepsia, ulcer disease, gastric outlet obstruction, cyclic vomiting, rumination, eating disorders, and chronic cannabis use. And how slowly the stomach empties correlates poorly with how bad the symptoms are. So gastroparesis requires proof of delayed emptying, without a mechanical obstruction.

6:13His first test is endoscopy, to exclude obstruction. It comes before any emptying study, because a pyloric or duodenal stricture causes exactly the same symptoms, and the treatment is completely different. A bezoar, retained food after a proper fast, or pyloric stenosis seen at endoscopy changes the pathway. Biopsies can look for H. pylori, eosinophilic disease, or infiltrative processes when the picture is atypical. Cross-sectional imaging or a small-bowel follow-through is added when malrotation, internal hernia, or outside compression is suspected. His endoscopy shows retained food in the stomach and no obstruction.

6:53Then comes gastric emptying scintigraphy, and how it's done decides whether it means anything. The standard meal is a low-fat egg-white sandwich, two hundred fifty-five kilocalories and two percent fat, with jam, white bread, and water, labeled with technetium ninety-nine m sulfur colloid. It's eaten after an overnight fast, with images at zero, one, two, and four hours. The four-hour image is essential, because shorter studies vary too much in normal people to be diagnostic.

7:24The result is read at four hours, and the grade guides treatment. More than ten percent of the meal left at four hours is delayed emptying, and more than sixty percent at two hours is also abnormal. Severity is graded by the four-hour retention: ten to fifteen percent is mild, fifteen to thirty-five is moderate, and over thirty-five is severe. The grade guides how intensively he's treated.

7:47The preparation is where most false results come from, so it's managed carefully. Prokinetics, metoclopramide, erythromycin, domperidone, and prucalopride, are held for forty-eight to seventy-two hours, or they speed emptying and hide the disease. Opioids, anticholinergics, cannabis, and tobacco are held for at least forty-eight hours, or they slow emptying and create disease that isn't there. GLP-1 agonists are held according to their half-life. Many protocols hold the daily drugs, liraglutide and dulaglutide, on the day of testing, and the weekly ones, semaglutide and tirzepatide, need a longer hold. And his glucose must be under two hundred at the start.

8:33Gastroparesis is overdiagnosed when those rules are broken, with a short study, unheld drugs, or high glucose. He holds his oxycodone and cannabis for two days, and his glucose is one hundred sixty when the study begins. His four-hour retention is forty-two percent, which is severe gastroparesis.

8:52An alternative test exists for some patients. When scintigraphy isn't available, or when small bowel and colon transit matter too, a wireless motility capsule records pH and pressure as it passes and measures transit through each region. A gastric emptying time over five hours fits gastroparesis. Its risks are retention in a stricture or severe motility disorder, and it isn't widely available.

9:17A few more tests look for the cause. A1c and fasting glucose screen for diabetes, and thyroid-stimulating hormone, TSH, excludes hypothyroidism. When the history suggests it, antinuclear and scleroderma antibodies, anti-Scl-70, anticentromere, and anti-RNA polymerase three, are sent, with an exam for skin changes and Raynaud. Antineuronal nuclear antibodies, ANNA-1 and ANNA-2, with a chest computed tomography, CT, look for small cell lung cancer or thymoma when onset is acute, weight loss is out of proportion, or the small bowel is involved too. Antroduodenal manometry is kept for an unclear diagnosis or suspected pseudo-obstruction.

10:03The second patient shows the most common pitfall today. A fifty-two-year-old woman started semaglutide for weight loss three months ago and has had nausea and early fullness since. A scintigraphy study done without stopping the drug shows delayed emptying. That result doesn't prove gastroparesis, because the drug delays emptying in people whose stomachs are otherwise normal. So the semaglutide is stopped, and she's watched. If her symptoms resolve, she needs no further testing. Only if they persist is the study repeated off the drug.

10:33With his severe gastroparesis proven, treatment starts with the simplest steps, which are also the most effective. His fluids, electrolytes, and nutrition are corrected. His glucose control is improved, because hyperglycemia itself slows emptying. And the drugs that slow his stomach are stopped. He's referred for pain management to come off oxycodone, counseled to stop cannabis, and his insulin is adjusted with his endocrinologist. A fair number of patients labeled with gastroparesis are simply on one of those drugs.

11:04Diet comes next, and it works better than most clinicians expect. Meals are small and frequent, about six a day, because a smaller volume asks less of a failing pump and of a stomach that can't accommodate. They're low in fat, under about forty grams a day, because fat slows emptying through cholecystokinin. And they're low in insoluble fiber, because indigestible fiber forms bezoars in a stomach that can't clear it.

11:30As severity rises, the diet becomes more liquid, then bypasses the stomach. It moves to nutrition drinks, then blended foods, then feeding beyond the stomach. Jejunal feeding is considered for weight loss of ten percent or more over three to six months, or for repeated hospitalizations. It goes into the jejunum, past the stomach that isn't working, often through a combined tube with a gastric port for venting and a jejunal port for feeding. His fifteen pounds is close to that line, so his weight is watched closely.

12:02Prokinetics come after that foundation, and metoclopramide comes first. It's the only Food and Drug Administration, FDA, approved drug for gastroparesis, approved in nineteen seventy-nine. It blocks dopamine D two receptors, which improves the coordination of the antrum and duodenum and acts as an antiemetic in the brain's vomiting center. It also weakly stimulates serotonin four receptors, increasing acetylcholine release in the gut wall. The dose is five to ten milligrams three to four times a day, thirty minutes before meals and at bedtime, and it can be given by mouth, intravenously, subcutaneously, sublingually, or intranasally.

12:41Its side effects set a time limit. Its boxed warning for tardive dyskinesia limits treatment to twelve weeks, so he's reassessed then, and the drug is stopped or held when possible. Reversible movement side effects, parkinsonism, akathisia, and dystonia, occur in about ten percent, while irreversible tardive dyskinesia is rare. And blocking dopamine raises prolactin, causing galactorrhea and missed periods.

13:09Domperidone avoids the movement problems but adds a cardiac one. It also blocks D two receptors but doesn't enter the brain, so it avoids the movement disorders. Its risk is QT prolongation and sudden cardiac death. So it needs a baseline electrocardiogram, ECG, with a QTc under four hundred fifty milliseconds in men and four hundred seventy in women, plus monitoring. The dose is ten milligrams three to four times a day before meals and at bedtime, up to eighty milligrams a day. It isn't FDA-approved and is available only through an expanded-access program.

13:47Erythromycin works best in the hospital. It stimulates motilin receptors and triggers strong antral contractions, the third phase of the fasting motor pattern. Intravenous erythromycin, three milligrams per kilogram every eight hours, is the most effective prokinetic for an acute flare. By mouth, at one hundred twenty-five to two hundred fifty milligrams three times a day before meals, its effect fades within weeks to a few months as the motilin receptors down-regulate. It isn't an antiemetic, it prolongs the QT interval, and it interacts with drugs metabolized like macrolides, so stacking it with other QT-prolonging drugs takes care.

14:25Prucalopride is an option when constipation coexists, though the guidelines disagree. It's a selective serotonin four agonist approved for chronic constipation at two milligrams once daily, or one milligram over age sixty-five, and it's used off label in gastroparesis. The twenty twenty-two American College of Gastroenterology, ACG, guideline conditionally suggests it. The twenty twenty-five American Gastroenterological Association, AGA, guideline conditionally recommends against it as first-line therapy. The older serotonin four agonists, cisapride and tegaserod, were withdrawn for cardiovascular concerns.

15:02His nausea is treated alongside, and his weight loss shapes the choice. Promethazine or prochlorperazine suit mild to moderate disease, and both are phenothiazines that share the movement risk of metoclopramide. Ondansetron, a serotonin three antagonist, is for moderate to severe nausea, with a QT caution. Mirtazapine blocks serotonin three receptors to treat nausea and histamine receptors to stimulate appetite, which makes it a good choice in a patient who's losing weight, like him.

15:32Two other symptom drugs have weaker support. Aprepitant, a neurokinin one antagonist, is used for refractory nausea, though the AGA is conditionally against routine use. A low-dose tricyclic, with nortriptyline favored for tolerability, can help pain and nausea from heightened sensitivity. The AGA is conditionally against routine use, but it's a reasonable add-on for refractory symptoms.

15:57He starts small, frequent, low-fat meals, liquid supplements, metoclopramide before meals, and mirtazapine at bedtime. Off oxycodone and cannabis, with better glucose control, his vomiting stops and he regains weight.

16:12A patient who stays severely symptomatic despite all of that has refractory gastroparesis, and the procedural options are limited. Botulinum toxin into the pylorus didn't beat placebo in controlled trials and isn't recommended. Gastric electrical stimulation, a neurostimulator implanted on the stomach, reduces nausea and vomiting in some diabetic patients whose main symptoms are nausea and vomiting rather than pain, especially those with frequent hospitalizations.

16:39Gastric stimulation has clear limits. Its mechanism is unknown, and it doesn't pace the stomach or speed emptying. Nondiabetic patients whose main problem is pain, or who take opioids, respond poorly. The AGA is conditionally against it as a routine intervention, because sham-controlled trials are lacking.

17:00The pylorus is the newer target. Gastric peroral endoscopic myotomy, G-POEM, cuts the pyloric muscle through a submucosal tunnel, and it helps fifty to sixty percent of patients in open-label series at a year. Response is predicted by marked retention, more than twenty percent at four hours, and a high baseline gastroparesis cardinal symptom index. The AGA conditionally recommends it only in highly selected refractory patients.

17:25Surgery is kept for the most refractory cases. Surgical pyloroplasty and completion gastrectomy remain options but carry significant morbidity. A venting gastrostomy with a jejunal feeding port supports nutrition and decompression without resection.

17:40The current AGA guideline, in summary, conditionally supports metoclopramide and erythromycin. It's conditionally against routine domperidone, nortriptyline, aprepitant, buspirone, and prucalopride, with prucalopride acceptable when constipation coexists and cannabidiol limited to trials. It's conditionally against routine gastric electrical stimulation, pyloric botulinum toxin, and surgical pyloroplasty, and it keeps G-POEM for selected refractory patients.

18:13Here are the traps the boards set in this patient. Gastroparesis isn't diagnosed from symptoms, and endoscopy isn't skipped. A study shorter than four hours isn't diagnostic. Testing isn't done on opioids, cannabis, or a GLP-1 agonist, or with a glucose over two hundred. And a patient whose symptoms resolved off semaglutide doesn't need the study repeated.

18:35The treatment traps close the list. Drugs don't come before fixing diet, glucose, and medications. Metoclopramide isn't continued past twelve weeks without reassessment. Domperidone isn't started without an ECG. Oral erythromycin stops working over time. And botulinum toxin isn't injected into the pylorus.

18:56So, start to finish. Emptying needs the vagus, the interstitial cells of Cajal, and working muscle. Diabetes damages the first two, and drugs, especially opioids, cannabis, and GLP-1 agonists, are the most common fixable cause.

19:12Exclude obstruction with endoscopy, then do a four-hour solid-meal scintigraphy with medications held and glucose under two hundred. Over ten percent left at four hours is delayed, with ten to fifteen percent mild, fifteen to thirty-five moderate, and over thirty-five severe.

19:28Treat by fixing fluids, glucose, and drugs, then small frequent low-fat, low-fiber meals, moving to liquids and jejunal feeding as needed. Metoclopramide is the only approved prokinetic, with a twelve-week limit. Intravenous erythromycin is best for acute flares. For refractory disease, pyloric myotomy is offered to selected patients with marked retention.

19:51Episode two is vomiting that comes in discrete attacks, from cyclic vomiting syndrome or daily cannabis, then intestinal pseudo-obstruction and functional dyspepsia.

20:01For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of two of chapter eight, and I'll see you in the next one.