Gastrointestinal

Gastroparesis: diagnosis and management

Clinical Overview and When to Suspect Gastroparesis

— Diabetic (most commonly tested): long-standing T1DM > T2DM, usually with other microvascular complications (retinopathy, neuropathy, nephropathy); poor glycemic control accelerates gastroparesis and vice versa

— Idiopathic (~36%): often young/middle-aged women, sometimes post-viral

— Postsurgical: vagal injury from fundoplication, bariatric surgery, esophagectomy, lung transplant, partial gastrectomy

— Medication-induced: GLP-1 agonists, amylin analogs (pramlintide), opioids, anticholinergics, TCAs, CCBs, cyclosporine

— Acute onset → think obstruction, gastritis, gastroenteritis, DKA

— Red flags (hematemesis, melena, dysphagia, age >55 new-onset, weight loss without other features) → endoscopy first

— Symptoms localized to RUQ or with jaundice → biliary

Definition: objectively delayed gastric emptying in the absence of mechanical obstruction, producing chronic upper GI symptoms

Core triad to suspect: nausea/vomiting + early satiety/postprandial fullness + bloating, lasting ≥3 months with onset ≥6 months prior

Epidemiology and high-yield etiologies (memorize the "Big 4"):

Other contributors: scleroderma/connective tissue disease, hypothyroidism, Parkinson disease, amyloidosis, paraneoplastic (small cell lung cancer with anti-Hu antibodies), chronic mesenteric ischemia, autonomic neuropathy

Step 3 ambulatory framing: the typical stem is a diabetic with A1c >9%, weight loss, recurrent ED visits for nausea/vomiting, and erratic glucose control (especially unexplained postprandial hypoglycemia from food not entering the duodenum on schedule)

When NOT to suspect gastroparesis first:

Board pearl: Before labeling a patient "gastroparesis," you must first exclude mechanical obstruction (EGD) and stop offending drugs — diagnosis is otherwise invalid and gastric emptying studies will be misleading.

Presentation Patterns and Key History

— Nausea ~90%, vomiting ~70% (often of undigested food eaten hours earlier — a classic clue)

— Early satiety and postprandial fullness ~60–80%

— Bloating, upper abdominal pain (not the dominant symptom — if pain dominates, reconsider functional dyspepsia or biliary)

— Weight loss, malnutrition, dehydration

— Symptoms worse after solid, fatty, fiber-rich meals; better with liquids

— Vomiting often >1 hour after eating (vs. gastric outlet obstruction which is immediate, or rumination which is within minutes and effortless)

— Diabetic gastroparesis: erratic glycemia, postprandial hypoglycemia followed by late hyperglycemia

— Diabetes duration, A1c trend, microvascular complications, GLP-1/pramlintide use

— Prior abdominal/thoracic surgery, fundoplication, bariatric procedures

— Medication review: opioids, anticholinergics, TCAs, dihydropyridine CCBs, cannabinoids, GLP-1 RAs

— Connective tissue symptoms (Raynaud, skin tightening) → scleroderma

— Thyroid symptoms, Parkinson features, autonomic symptoms (orthostasis, erectile dysfunction)

— Mood/eating disorder screen — overlap with anorexia/bulimia; rumination syndrome mimics

Cardinal symptoms (frequency in idiopathic/diabetic cohorts):

Temporal pattern to elicit:

Targeted history checklist (Step 3 ambulatory visit):

Validated symptom tool: Gastroparesis Cardinal Symptom Index (GCSI) — used to track severity and response, not for diagnosis

Red flags mandating urgent workup rather than empiric trial: hematemesis, melena, dysphagia, GI bleeding, persistent vomiting with dehydration/AKI, new mass, unintentional weight loss >5%

Key distinction: Cyclic vomiting syndrome and cannabinoid hyperemesis present with discrete episodic vomiting separated by completely asymptomatic intervals — gastroparesis is continuous low-grade symptoms with meal-related exacerbations. Ask about chronic cannabis use and relief with hot showers.

Physical Exam Findings and Hemodynamic Assessment

— Orthostatic vitals — supine→standing drop ≥20 mmHg SBP or ≥10 mmHg DBP or HR rise ≥30

— Mucous membranes, skin turgor, capillary refill, JVP

— In diabetics: orthostasis may also reflect autonomic neuropathy independent of volume — check HR response to standing (blunted in autonomic failure)

— Succussion splash >3 hours after eating = retained gastric contents (highly suggestive but not specific; also seen in gastric outlet obstruction)

— Epigastric tenderness mild; distension common; bowel sounds usually normal or sluggish

— Importantly no peritoneal signs — if present, look for alternative diagnosis (perforation, ischemia, pancreatitis)

— Diabetic: retinopathy on fundoscopy, peripheral neuropathy (monofilament, vibration), Charcot foot, postural hypotension

— Scleroderma: sclerodactyly, telangiectasias, calcinosis, Raynaud, tight facial skin

— Parkinson: resting tremor, cogwheel rigidity, bradykinesia

— Amyloidosis: macroglossia, periorbital purpura, carpal tunnel

— Thyroid: goiter, delayed reflex relaxation (hypothyroid)

— Weight, BMI, recent weight trajectory

— Albumin/prealbumin trend

— Look for B12, iron, vitamin D, thiamine deficiency stigmata (glossitis, neuropathy, pallor)

General appearance: thin, sometimes cachectic; assess for sarcopenia and temporal wasting in chronic cases

Volume status (critical at every visit):

Abdominal exam:

Look for clues to etiology:

Dental exam: enamel erosion suggests chronic vomiting (also bulimia)

Nutritional assessment:

CCS pearl: Order orthostatic vitals, weight, and a finger-stick glucose at every gastroparesis follow-up visit — these three numbers drive almost every management decision (admit vs. outpatient, adjust insulin, escalate antiemetic).

Diagnostic Workup — Initial Labs, Imaging, and Exclusions

— EGD is mandatory before diagnosing gastroparesis; rules out gastric outlet obstruction, peptic ulcer, malignancy, bezoar

— Retained food >12 hours after fasting on EGD strongly supports delayed emptying (but EGD is not the confirmatory test)

— Consider CT or MR enterography if distal obstruction suspected; small bowel follow-through if dysmotility distal to stomach considered

— CBC, CMP (electrolyte derangements from vomiting: hypokalemia, hypochloremic metabolic alkalosis, AKI)

— HbA1c and glucose — must optimize glycemia before/during emptying study (acute hyperglycemia >200 mg/dL delays gastric emptying and invalidates results)

— TSH (hypothyroidism)

— Pregnancy test in reproductive-age women (rules out hyperemesis gravidarum and is a contraindication to several therapies)

— ANA, scleroderma panel if connective tissue features

— Consider celiac serology, B12, iron studies, vitamin D

— Stop opioids, GLP-1 agonists, pramlintide, anticholinergics for ≥48–72 hours before any emptying study

— Hold promotility agents and antiemetics that affect motility

— Plain film/CT may show gastric distension with retained food/air-fluid levels

— RUQ ultrasound if biliary pain features

Step 1 — Exclude mechanical obstruction and mucosal disease:

Step 2 — Initial laboratory panel:

Step 3 — Medication reconciliation:

Imaging adjuncts:

Board pearl: A gastric emptying study performed during hyperglycemia (>200 mg/dL), on a GLP-1 agonist, or on opioids is uninterpretable — these all delay emptying physiologically. Fix the confounders first or the test result is meaningless.

Key distinction: EGD finding of retained food after appropriate fast is suggestive, not diagnostic — you still need a quantitative emptying study to confirm and grade severity.

Diagnostic Workup — Advanced and Confirmatory Studies

— Standardized low-fat, egg-white meal with Tc-99m labeling (per consensus protocol)

— Measure retention at 1, 2, and 4 hours

— Diagnostic criteria (any one): >60% retention at 2 h, >10% retention at 4 h

— Severity grading:

— Mild: 11–20% at 4 h

— Moderate: 21–35% at 4 h

— Severe: >35% at 4 h

— Always perform off opioids/GLP-1s × ≥48–72 h and with glucose <200

— Wireless motility capsule (SmartPill): measures gastric emptying time, pH, pressure; useful when whole-gut dysmotility suspected; contraindicated with strictures, prior bezoar, swallowing disorders, gastric stimulator

— 13C-octanoate or 13C-spirulina breath test: noninvasive, no radiation; useful in pregnancy and pediatrics

— Antroduodenal manometry — if chronic intestinal pseudo-obstruction suspected (differentiates myopathic from neuropathic dysmotility)

— Autonomic function testing if autonomic neuropathy suspected and unconfirmed

— Endoscopic ultrasound or MRCP if biliary/pancreatic etiology unclear

— Barium studies are insensitive and not confirmatory

— EGG (electrogastrography) — not standard of care

Gold standard: 4-hour scintigraphic gastric emptying study (GES)

Alternative tests (when scintigraphy unavailable or equivocal):

Tests to exclude mimics:

What NOT to order routinely:

Step 3 management: A patient with classic diabetic symptoms, A1c 11%, retained food on EGD, and 45% retention at 4 hours on GES off opioids and with glucose 140 → diagnosis confirmed as severe diabetic gastroparesis; begin glycemic optimization + dietary modification + metoclopramide trial and re-image only if treatment failure.

Board pearl: The single most testable diagnostic number is >10% gastric retention at 4 hours on standardized scintigraphy = delayed emptying.

Risk Stratification and First-Line Management Logic

— Grade 1 (mild): symptoms easily controlled, weight/nutrition maintained → diet + glycemic control

— Grade 2 (compensated): moderate symptoms, partial control with pharmacotherapy, no frequent hospitalization → add prokinetic + antiemetic

— Grade 3 (refractory/gastric failure): unable to maintain nutrition/hydration orally, recurrent hospitalizations → enteral feeding, advanced therapies, consults

— Dietary modification (first-line, evidence-based):

— Small, frequent meals (4–5/day)

— Low-fat, low-insoluble-fiber (avoid raw vegetables, oranges, legumes — bezoar risk)

— Soft/blenderized or liquid-predominant when severe

— Chew thoroughly; sit upright 1–2 h after meals; walk after meals

— Glycemic optimization: target glucose <180 mg/dL; hyperglycemia worsens emptying; consider CGM in diabetics

— Discontinue offending medications: opioids, GLP-1 agonists, pramlintide, anticholinergics, dihydropyridine CCBs

— Hydration and electrolyte repletion

— Correct micronutrient deficiencies: B12, iron, vitamin D, thiamine

— Add prokinetic first (metoclopramide is FDA-approved)

— Add antiemetic for symptomatic vomiting (ondansetron, prochlorperazine)

— Escalate to second-line prokinetic (erythromycin, domperidone via FDA expanded access)

Severity-based framework (Abell classification — high-yield):

Initial outpatient steps for ALL patients (the "foundation"):

Choosing pharmacotherapy after diet/glycemic control fails:

CCS pearl: Before reaching for any drug, CCS-style orders should include: "diet — low-fat, low-fiber, small frequent meals," "discontinue opioid," "diabetes education," "nutrition consult," and "glucose monitoring q ac/hs." These non-pharmacologic orders are scored.

Board pearl: Glycemic control is both diagnostic and therapeutic — fixing A1c can resolve mild diabetic gastroparesis without any drug.

Pharmacotherapy — First-Line and Second-Line Regimens

— D2 antagonist + 5-HT4 agonist; prokinetic and central antiemetic

— Dose: 5 mg PO before meals and at bedtime, titrate to 10 mg QID; max 40 mg/day, max duration 12 weeks per FDA black-box

— Black-box warning: tardive dyskinesia — risk rises with dose, duration, age, female sex, diabetes

— Other AEs: drowsiness, anxiety/depression, QT prolongation, hyperprolactinemia (galactorrhea, gynecomastia), NMS, extrapyramidal symptoms

— Use liquid or ODT formulation if severe emptying delay (oral tablets may not dissolve)

— Obtain baseline ECG; avoid if QTc prolonged; review at each visit for abnormal movements (AIMS exam)

— Motilin receptor agonist — potent gastric prokinetic

— IV erythromycin 3 mg/kg q8h for acute inpatient management; PO 50–250 mg TID before meals for outpatient

— Tachyphylaxis within 4 weeks (motilin receptor downregulation) — best for short-term flares

— AEs: QT prolongation, ototoxicity, CYP3A4 interactions (statins, warfarin), C. difficile, abdominal cramping

— Peripheral D2 antagonist; available via FDA Investigational New Drug application

— Less CNS toxicity than metoclopramide; QT prolongation remains a concern — baseline and follow-up ECG

— Ondansetron 4–8 mg q8h PRN (watch QT)

— Prochlorperazine, promethazine (avoid in elderly — anticholinergic, EPS)

— Mirtazapine 15 mg qhs — helpful when weight loss/anorexia coexist

— Scopolamine and aprepitant in refractory cases

— TCAs (nortriptyline) for refractory nausea/pain — paradoxically used despite anticholinergic effect; low-dose preferred

— Avoid amitriptyline (most anticholinergic)

Metoclopramide (first-line, only FDA-approved drug):

Erythromycin (second-line / short-term):

Domperidone:

Antiemetics (symptomatic adjuncts, not prokinetic):

Adjuncts:

Step 3 management: Start metoclopramide ODT 5 mg AC/HS, reassess at 4 weeks; if no improvement, stop (limit TD risk) and trial erythromycin or refer.

Board pearl: Always document baseline ECG and AIMS before metoclopramide and at each follow-up.

Procedures and Advanced Therapies for Refractory Disease

— Intrapyloric botulinum toxin injection: historically used but RCTs show no benefit over placebo — not recommended as standard therapy (testable point)

— Gastric Per-Oral Endoscopic Myotomy (G-POEM/POP): endoscopic pyloromyotomy; promising for refractory cases, especially post-surgical and idiopathic; 60–80% short-term response

— Transpyloric stenting: bridge therapy in select centers

— Gastric electrical stimulation (Enterra device): FDA humanitarian device exemption for refractory diabetic and idiopathic gastroparesis; reduces nausea/vomiting more than emptying time; best response in diabetics

— Surgical pyloroplasty — for selected refractory patients, especially postsurgical vagal injury

— Subtotal or total gastrectomy — last resort, primarily postsurgical gastroparesis

— Oral → liquid supplements → jejunal enteral feeding (J-tube or GJ-tube) for sustained inability to maintain weight

— Avoid gastrostomy as feeding access (gastric stasis) — used only for venting

— Parenteral nutrition only when enteral fails — high infection/thrombosis risk

— Switch from GLP-1 RA and pramlintide to other agents

— Insulin pump with CGM improves matching to delayed absorption

— Consider post-meal short-acting insulin rather than pre-meal in severe delay

Indications for escalation: failure of dietary, glycemic, and 2 prokinetic trials with severe symptoms, malnutrition, or recurrent hospitalizations

Endoscopic interventions:

Surgical and device therapies:

Nutritional support hierarchy (Step 3 high-yield):

Glycemic management in diabetic gastroparesis:

Pain control challenge: avoid opioids — they worsen gastroparesis. Use TCAs, gabapentin, mirtazapine, behavioral approaches.

CCS pearl: When ordering nutrition, always specify "post-pyloric (jejunal) feeding tube" — a gastrostomy will not bypass the dysmotile stomach and will fail.

Board pearl: Botox into the pylorus = negative trials, do not select on exam.

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline risk of tardive dyskinesia, EPS, and delirium from metoclopramide — start at 2.5–5 mg, avoid >5 mg per dose, shorter duration

— Avoid promethazine and prochlorperazine (anticholinergic burden, falls, delirium — Beers criteria)

— Polypharmacy review: anticholinergics, opioids, CCBs are common offenders in this group

— Sarcopenia and frailty amplify malnutrition risk — earlier nutrition consult

— Watch for aspiration pneumonia from retained gastric contents — head of bed elevation, no late meals

— Metoclopramide is renally excreted — reduce dose by 50% if CrCl <40 mL/min; risk of accumulation → EPS, NMS

— Ondansetron — no significant renal adjustment; monitor QT

— Erythromycin — primarily hepatic; minor renal adjustment

— Diabetic patients often have CKD — recheck eGFR before titrating prokinetics

— Avoid magnesium-containing antacids in advanced CKD

— Erythromycin — hepatic metabolism, dose-reduce in severe disease; risk of cholestatic hepatitis (erythromycin estolate particularly)

— TCAs — reduce dose in cirrhosis (CYP metabolism)

— Domperidone — hepatic metabolism, avoid in severe impairment; QT risk amplified

— Erythromycin + statin (simvastatin, lovastatin) → rhabdomyolysis

— Erythromycin + warfarin → INR rise

— Erythromycin + QT-prolonging drugs (ondansetron, methadone, fluoroquinolones) → torsades

— Metoclopramide + SSRI/SNRI → serotonin syndrome and EPS additive

Elderly patients:

Renal impairment:

Hepatic impairment:

Drug interactions to recognize on the exam:

Step 3 management: In an 82-year-old with diabetic gastroparesis and CrCl 30, start metoclopramide 2.5 mg AC/HS with baseline ECG and AIMS; avoid promethazine; counsel family on tardive dyskinesia signs and stop drug at first abnormal movement.

Board pearl: Reduce metoclopramide 50% if CrCl <40 — commonly missed and frequently tested.

Special Populations — Pregnancy, Pediatrics, and Post-Surgical

— Gastric emptying is not typically delayed in normal pregnancy, but pre-existing gastroparesis can worsen — distinguish from hyperemesis gravidarum (early pregnancy, ketosis, weight loss >5%)

— Scintigraphy is contraindicated — use 13C breath test if confirmation needed

— Treatment hierarchy:

— Pyridoxine (B6) + doxylamine first-line for nausea/vomiting in pregnancy

— Metoclopramide — Category B, generally considered safe; preferred prokinetic

— Ondansetron — extensive use; small absolute risk of cleft palate if used in first trimester (counsel; benefit usually outweighs)

— Avoid erythromycin estolate (hepatotoxicity in pregnancy); base form acceptable short-term

— Monitor for dehydration, electrolytes, ketosis, and fetal growth

— Often post-viral, idiopathic, or associated with mitochondrial disorders

— Erythromycin commonly used; metoclopramide use limited due to TD/EPS risk

— Cyproheptadine is sometimes used for appetite and nausea

— Rule out cyclic vomiting syndrome, eosinophilic GI disease, and eating disorders

— Common after fundoplication, bariatric (especially sleeve), Whipple, lung/heart transplant, vagotomy

— Often improves over 6–12 months

— Consider G-POEM or pyloroplasty earlier in postsurgical phenotype — best procedural responders

— Optimize glycemic control preconception (gastroparesis worsens with pregnancy hormonal changes)

— Avoid GLP-1 agonists ≥2 months before conception

— Anorexia nervosa causes delayed gastric emptying that reverses with refeeding — do not commit to chronic gastroparesis label; refeed under supervision and reassess

Pregnancy:

Pediatrics:

Post-surgical gastroparesis:

Diabetic women of reproductive age:

Eating disorder overlap:

Board pearl: First-line antiemetics in pregnancy = pyridoxine + doxylamine; metoclopramide is the preferred prokinetic in pregnancy.

Key distinction: Anorexia-related delayed emptying resolves with weight restoration — don't start chronic prokinetics.

Complications and Adverse Outcomes

— Malnutrition, sarcopenia, micronutrient deficiencies (B12, iron, vitamin D, thiamine, fat-soluble vitamins)

— Refeeding syndrome risk on re-nutrition — replete phosphate, magnesium, potassium, thiamine before/during refeeding

— Weight loss >10% = severe disease, escalate to enteral feeding

— Hypokalemia, hypochloremic metabolic alkalosis from chronic vomiting

— Dehydration, prerenal AKI — common ED presentation

— Postprandial hypoglycemia (insulin given but food delayed) followed by late hyperglycemia

— Erratic A1c despite good adherence — clue to undiagnosed gastroparesis

— Increased DKA admissions

— Bezoar formation — high-fiber foods, pharmacobezoars (sucralfate, cholestyramine, psyllium); treat with Coca-Cola lavage, enzymatic dissolution, endoscopic disruption

— Mallory-Weiss tears from forceful emesis

— Esophagitis, dental erosion, halitosis

— Aspiration pneumonia / pneumonitis — especially in elderly, supine patients

— Depression, anxiety, opioid dependence (avoid initiating opioids)

— Disability, lost work productivity

— Frequent ED visits — cost driver

— Metoclopramide → tardive dyskinesia (often irreversible), EPS, NMS, depression

— Erythromycin → torsades, hepatotoxicity, C. difficile

— Enteral tubes → infection, dislodgement, leakage

— TPN → CLABSI, hepatic steatosis, thrombosis

— Gastroparesis itself rarely fatal; mortality driven by underlying disease (diabetes, scleroderma) and complications (aspiration, malnutrition, DKA)

Nutritional and metabolic:

Fluid/electrolyte:

Glycemic instability in diabetics:

Mechanical complications:

Quality of life and psychiatric:

Treatment-related:

Mortality:

Step 3 management: In a diabetic with recurrent DKA and gastroparesis, the gastroparesis must be addressed (insulin timing, diet, prokinetic) — DKA prevention is otherwise impossible.

Board pearl: Bezoars form on high-fiber diets — counsel against raw vegetables, oranges, persimmons; treat refractory bezoars endoscopically.

When to Escalate Care — ICU, Consult, and Inpatient Triage

— Tolerating oral intake/hydration

— No severe electrolyte derangement or AKI

— Stable weight and vitals

— Diabetes reasonably controlled

— Intractable vomiting with dehydration, AKI, or electrolyte abnormalities

— Weight loss >5–10% requiring nutritional rescue

— Diabetic with recurrent hypo/hyperglycemia or DKA precipitated by gastroparesis

— Inability to tolerate oral medications/insulin

— Bezoar requiring endoscopy

— Initiation of jejunal feeding

— Hemodynamic instability from volume loss

— Severe DKA or HHS

— Aspiration pneumonia with respiratory failure

— Severe electrolyte derangement with arrhythmia (hypokalemia + QT prolongation on QT-prolonging antiemetics)

— IV fluids — normal saline initially, then balanced crystalloid; replete K, Mg, phosphate

— NG decompression if marked gastric distension or persistent vomiting

— IV antiemetics: ondansetron 4 mg q6h (telemetry for QT), prochlorperazine

— IV erythromycin 3 mg/kg q8h — most potent acute prokinetic

— IV metoclopramide if erythromycin contraindicated

— Hold offending drugs (opioids, GLP-1)

— Insulin: IV infusion if DKA; otherwise basal-bolus with post-meal short-acting insulin

— Nutrition consult; consider nasojejunal tube within 48–72 hours if oral fails

— GI — confirm diagnosis, EGD, advanced therapies

— Endocrinology — glycemic management

— Nutrition — diet, enteral access

— Surgery/interventional GI — pyloroplasty, G-POEM, feeding tube

— Psychiatry — disordered eating overlap, depression

— Tolerating goal diet (often liquid/soft) × 24 hours

— Stable electrolytes, hydration, glucose

— Follow-up arranged within 1–2 weeks

Outpatient management is appropriate when:

Admit to floor when:

ICU criteria:

Inpatient management priorities (CCS order set):

Consults to anticipate:

Discharge readiness criteria:

CCS pearl: On CCS, always stop the home opioid and GLP-1 on admission orders — these are scored interventions and addressing them often resolves the flare alone.

Key Differentials — Same-Category (Upper GI Functional/Motility)

— Overlapping symptoms (early satiety, postprandial fullness, epigastric discomfort)

— Normal gastric emptying — distinguishing test

— Treat with PPI, H. pylori eradication, low-dose TCA, prokinetics

— Mechanical (peptic stricture, malignancy, pancreatic mass, SMA syndrome)

— Vomiting immediately after meals, weight loss, succussion splash

— EGD shows obstruction — gastroparesis requires no obstruction

— Effortless regurgitation of recently ingested food within minutes (not hours) of eating, re-chewed and swallowed/spat

— No nausea preceding the event

— Diagnosed clinically/manometrically; treat with diaphragmatic breathing therapy

— Stereotyped discrete episodes of intense vomiting lasting hours–days, separated by completely asymptomatic intervals

— Migraine association; prophylaxis with TCAs, topiramate; abortive sumatriptan

— Chronic heavy cannabis use, cyclical vomiting, compulsive hot-water bathing relieves symptoms

— Treatment: cannabis cessation; topical capsaicin; haloperidol in acute episode

— Diffuse dysmotility, dilated bowel loops on imaging, often with bladder involvement (megacystis)

— Antroduodenal manometry differentiates from gastroparesis alone

— Coexist often; treat GERD with PPI, lifestyle; consider emptying study if severe regurgitation

— Peripheral eosinophilia, biopsy with eosinophilic infiltrate

— Vomiting minutes after meal → rumination

— Vomiting immediately after meal → outlet obstruction

— Vomiting hours after meal of undigested food → gastroparesis

— Episodic stereotyped vomiting with well intervals → CVS or cannabinoid hyperemesis

Functional dyspepsia (postprandial distress syndrome):

Gastric outlet obstruction:

Rumination syndrome:

Cyclic vomiting syndrome:

Cannabinoid hyperemesis syndrome:

Chronic intestinal pseudo-obstruction:

GERD with delayed emptying:

Eosinophilic gastroenteritis:

Board pearl: Three-second discriminators on the exam:

Key Differentials — Other-Category (Non-GI Mimics)

— Diabetic ketoacidosis — acute nausea/vomiting/abdominal pain with hyperglycemia and acidosis; check anion gap, beta-hydroxybutyrate before attributing to gastroparesis

— Adrenal insufficiency — nausea, vomiting, hypotension, hyperkalemia, hyponatremia

— Hypercalcemia — nausea, constipation, AMS

— Uremia in advanced CKD

— Hypothyroidism (can also cause gastroparesis but as a mimic — fatigue, constipation, weight gain)

— Increased intracranial pressure — morning vomiting, headache, papilledema

— Vestibular disorders — vertigo-associated vomiting

— Migraine — aura, photophobia, throbbing headache

— Opioid-induced nausea

— Chemotherapy-induced nausea/vomiting

— Digoxin toxicity — nausea + visual changes + arrhythmia

— Alcohol use disorder, cannabis hyperemesis

— Hyperemesis gravidarum (first trimester, ketones, weight loss >5%)

— Preeclampsia with HELLP — RUQ pain, hypertension, proteinuria

— Inferior MI — nausea/vomiting/epigastric pain — always check ECG in older patients with new "GI" symptoms, especially diabetics

— Pancreatitis (lipase), cholecystitis (RUQ US), small bowel obstruction (imaging), appendicitis, mesenteric ischemia (postprandial pain "food fear," weight loss — can mimic gastroparesis closely in elderly vasculopaths)

— Anorexia nervosa, bulimia, somatic symptom disorder

— Anti-Hu, anti-PCA-1 antibodies — small cell lung cancer; consider in older smokers with new gastroparesis

Endocrine/metabolic:

CNS causes:

Medication/toxin:

Pregnancy-related:

Cardiac:

Surgical abdomen:

Psychiatric:

Paraneoplastic:

Step 3 management: In an elderly diabetic smoker with new gastroparesis and weight loss, order CT chest and consider paraneoplastic antibody panel — don't anchor on diabetic gastroparesis.

Board pearl: Always rule out DKA and MI before assuming a diabetic patient's vomiting is gastroparesis.

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Prokinetic: metoclopramide 5–10 mg AC/HS (lowest effective dose, ≤12 weeks at a time), or domperidone if available

— Antiemetic PRN: ondansetron 4–8 mg q8h PRN (warn QT)

— Diabetes regimen: revised insulin schedule with post-prandial short-acting insulin; CGM if feasible; stop GLP-1 RA and pramlintide

— PPI if reflux/esophagitis

— Replete electrolytes and micronutrients: oral potassium, magnesium, B12, vitamin D, thiamine, iron as indicated

— Avoid opioids for any pain; if needed, use tramadol cautiously or non-opioid alternatives (acetaminophen, TCAs, gabapentin)

— Written diet plan: small, frequent, low-fat, low-fiber meals (4–5/day); liquid-predominant during flares

— Walk after meals; sit upright 1–2 hours postprandially; no late-night meals (aspiration risk)

— Smoking and alcohol cessation

— Avoid carbonated beverages

— A1c <7% if no hypoglycemia risk; <8% if frail, elderly, or hypoglycemia-prone

— Glucose <180 mg/dL postprandial to avoid worsening emptying

— PCP within 1–2 weeks

— GI within 4 weeks

— Endocrinology within 2–4 weeks

— Nutrition follow-up

— Behavioral health if depression/anxiety/disordered eating

— Recognize warning signs: weight loss, dehydration, recurrent vomiting, hypoglycemia

— Sick day rules for diabetics

— Medication side effect awareness (TD with metoclopramide — return for any abnormal movements)

Discharge medication checklist:

Lifestyle and dietary plan:

Vaccinations if planning advanced therapies (gastric stimulator, transplant): pneumococcal, influenza, COVID, hepatitis B

Glycemic targets:

Connect to ongoing care:

Patient education:

Step 3 management: Always document a stop date for metoclopramide (12 weeks) and AIMS exam at each visit — this is a scored safety behavior and a high-yield malpractice topic.

Board pearl: Long-term opioid avoidance is the single most effective secondary prevention measure for gastroparesis flares.

Follow-Up, Monitoring, and Counseling

— 2 weeks post-discharge — weight, hydration, glucose, symptom response, medication tolerance

— 4 weeks — reassess metoclopramide efficacy; if no response, discontinue and escalate

— Every 3 months thereafter for stable patients; more frequent if labile

— Weight, BMI, weight trajectory

— Orthostatic vitals

— GCSI score (track severity over time)

— A1c every 3 months until stable, then every 6 months

— CMP, magnesium, phosphate; B12, vitamin D annually; iron studies if anemic

— ECG annually while on metoclopramide, erythromycin, ondansetron, or domperidone (QT)

— AIMS exam every visit on metoclopramide

— Bone density in chronic malnutrition

— Repeat GES not routinely needed if clinically improving

— Repeat EGD if new red flags (bleeding, dysphagia, anemia) or suspicion of bezoar

— Consider repeat GES if considering invasive therapy (G-POEM, stimulator)

— Realistic expectations — symptom improvement, not cure; chronic relapsing course

— Self-monitoring of weight (weekly), glucose, hydration

— Trigger foods and dietary diary

— Mental health — high comorbidity with anxiety/depression; consider CBT, antidepressants (mirtazapine doubles as antiemetic and appetite stimulant)

— Driving and occupational safety with metoclopramide-related sedation

— Sick day plan for diabetics — when to escalate, when to call, when to come in

— Pulmonary rehab if aspiration pneumonia history

— Physical therapy for sarcopenia

— Support groups (G-PACT, IFFGD)

— Social work for disability, FMLA, insurance navigation

Visit cadence:

Monitoring parameters at each visit:

When to re-image:

Counseling priorities:

Rehabilitation and support:

CCS pearl: Schedule the 2-week follow-up before discharge — late follow-up after a gastroparesis admission is the most common readmission driver.

Board pearl: AIMS + ECG at every metoclopramide visit — non-negotiable safety net.

Ethical, Legal, and Patient Safety Considerations

— FDA black-box warning for tardive dyskinesia mandates explicit discussion and documentation: risk, irreversibility, ≤12-week duration limit, symptoms to monitor

— Document patient comprehension; obtain written informed consent in many institutions

— Tardive dyskinesia is a frequent source of malpractice litigation — failure to warn, failure to monitor (AIMS), and prescribing beyond 12 weeks are the three most cited deviations

— Patients with chronic nausea/pain are vulnerable to opioid initiation; opioids worsen gastroparesis and create dependence

— Use state PDMP (Prescription Drug Monitoring Program — mandatory in most states) before any controlled substance

— Co-prescribe naloxone if opioids are unavoidable

— High-risk handoffs: ED → floor, floor → home, especially with new insulin regimen and diet changes

— Use teach-back to confirm understanding of insulin adjustment with delayed gastric emptying — postprandial hypoglycemia from pre-meal insulin is a sentinel safety event

— Medication reconciliation at every transition — confirm GLP-1 and opioid discontinuation propagated to outpatient records

— Refractory gastroparesis patients may face decisions about J-tube placement, TPN, gastric stimulator, gastrectomy — ensure capacity assessment and advance directives addressing artificial nutrition

— Adolescents with eating disorder overlap → involve family, ethics, child psychiatry; balance autonomy with safety

— If eating disorder or self-induced vomiting suspected in a minor with significant malnutrition → mandatory child protective services involvement in many states when caregivers refuse evaluation

— Gastroparesis disproportionately affects women and uninsured diabetics; ensure access to CGM, nutrition counseling, and advanced therapies regardless of insurance status; advocate for patient assistance programs

Informed consent for metoclopramide:

Opioid stewardship:

Transitions of care:

Decision-making capacity:

Mandatory reporting:

Health equity:

Step 3 management: When stopping a GLP-1 agonist for gastroparesis, coordinate insulin or alternative agent BEFORE discontinuation — abrupt withdrawal without replacement causes hyperglycemic crisis. Document the handoff plan to the PCP.

High-Yield Associations and Rapid-Fire Clinical Facts

— Scleroderma — esophageal dysmotility + gastroparesis + small bowel dysmotility + bacterial overgrowth

— Parkinson disease — gastroparesis worsens levodopa absorption → motor fluctuations

— Amyloidosis — autonomic + GI + cardiac + renal

— Paraneoplastic (small cell lung) — anti-Hu antibodies

— POTS — overlapping autonomic features in young women

— Opioids, GLP-1 agonists, pramlintide, anticholinergics, TCAs, dihydropyridine CCBs, clonidine, cyclosporine, lithium, cannabis, alcohol

— Metoclopramide, erythromycin, domperidone, prucalopride (off-label), cisapride (withdrawn — QT)

— Metoclopramide ≤12 weeks

— Erythromycin tachyphylaxis at ~4 weeks

— Don't do GES if glucose >200, on opioid, on GLP-1, or pregnant

— Don't use SmartPill with strictures or stimulators

— Pyloric Botox → NOT effective

— G-POEM → effective in selected refractory patients

— Gastric stimulator → reduces nausea/vomiting, especially diabetic

— Gastrostomy for feeding → wrong answer (use jejunostomy)

Most common cause overall: idiopathic; most common identifiable cause: diabetes (long-standing, poorly controlled)

Diagnostic threshold: >10% retention at 4 hours on standardized scintigraphy (or >60% at 2 hours)

Conditions to recall fast:

Drugs that delay emptying (memorize):

Drugs that accelerate emptying:

Foods that worsen symptoms / form bezoars: persimmons, oranges, raw vegetables, legumes, high-residue fiber

Diet remedy: small, frequent, low-fat, low-insoluble-fiber, soft/liquid

Drug stop dates:

Test contraindications/confounders:

Procedure efficacy ranking (boards):

Glycemic pearl: Hyperglycemia >200 acutely delays emptying — control glucose first

Pregnancy first-line antiemetic: pyridoxine + doxylamine

Bezoar treatment: cellulase, papain, Coca-Cola lavage, endoscopic disruption

Board pearl: If the question shows a diabetic with postprandial hypoglycemia followed by late hyperglycemia and erratic A1c → think gastroparesis.

Board Question Stem Patterns

— 45-year-old woman, T1DM 20 years, retinopathy, neuropathy, A1c 10.5%, 3 months of nausea, vomiting undigested food eaten hours earlier, early satiety, 10-lb weight loss, erratic glucose

— Best next step: EGD to rule out obstruction → gastric emptying scintigraphy off opioids with glucose <200

— Best initial therapy: dietary modification + glycemic optimization + metoclopramide 5 mg AC/HS

— Patient with T2DM started on semaglutide 3 months ago, now with nausea and early satiety

— Answer: discontinue the GLP-1 agonist; symptoms usually resolve

— Refractory gastroparesis, "what is the most evidence-based intervention?" → NOT intrapyloric botox (negative trials); correct answers include G-POEM or gastric stimulator depending on options

— Severe gastroparesis with weight loss requiring enteral nutrition → jejunostomy tube, not gastrostomy

— Patient on metoclopramide × 8 months develops involuntary lip-smacking and tongue movements → tardive dyskinesia; discontinue immediately, document AIMS, consider valbenazine

— Diabetic with hot showers relieving vomiting + chronic cannabis use → cannabinoid hyperemesis, not gastroparesis

— Effortless regurgitation of food within minutes → rumination

— Episodic stereotyped vomiting with well intervals → cyclic vomiting syndrome

— Pregnant patient with known gastroparesis worsening → pyridoxine + doxylamine first; metoclopramide if needed; avoid scintigraphy

— GES ordered while patient on hydrocodone and glucose 280 — shows delayed emptying → uninterpretable; correct offenders and repeat

— Gastroparesis patient with new acute severe symptoms, EGD shows phytobezoar → endoscopic disruption + Coca-Cola lavage + dietary fiber restriction

— Diabetic gastroparesis with recurrent postprandial hypoglycemia on pre-meal lispro → shift short-acting insulin to post-meal dosing

Stem 1 — Classic diabetic gastroparesis:

Stem 2 — Medication-induced:

Stem 3 — Wrong procedure trap:

Stem 4 — Tube feeding choice:

Stem 5 — Metoclopramide complication:

Stem 6 — Differential anchor:

Stem 7 — Pregnancy:

Stem 8 — Confounded test:

Stem 9 — Bezoar:

Stem 10 — Insulin timing:

Board pearl: When stem mentions A1c >10 with classic symptoms, the prokinetic answer waits — fix glucose and diet first.

One-Line Recap

Gastroparesis is delayed gastric emptying without mechanical obstruction, diagnosed by >10% retention at 4 hours on standardized scintigraphy after excluding mechanical and pharmacologic causes, and managed in tiers: diet + glycemic control + offending drug removal → metoclopramide (≤12 weeks with AIMS/ECG monitoring) → erythromycin or domperidone → G-POEM, gastric stimulator, or jejunal feeding for refractory disease.

Diagnostic anchor: EGD first to rule out obstruction; 4-hour scintigraphy off opioids/GLP-1 with glucose <200; >10% retention at 4 h = diagnostic.

Management anchor: Diet (small, frequent, low-fat, low-fiber) + glycemic control (<180 mg/dL) + stop offending drugs (opioids, GLP-1 RA, pramlintide, anticholinergics) before any pharmacotherapy; metoclopramide is the only FDA-approved drug — start low, limit to 12 weeks, document AIMS and ECG every visit.

Safety anchor: Tardive dyskinesia with metoclopramide is a black-box, litigation-prone risk — informed consent, written documentation, time-limited prescribing, regular AIMS monitoring; opioids are both a cause and a worsener of gastroparesis — avoid them.

Differential anchor: Vomiting hours after meals of undigested food = gastroparesis; minutes and effortless = rumination; immediately after meals = outlet obstruction; episodic with well intervals = CVS or cannabinoid hyperemesis (hot showers, cannabis history); always rule out DKA and inferior MI in diabetics with new "GI" symptoms.

Step 3 longitudinal anchor: Schedule 2-week post-discharge follow-up, target A1c <7–8%, monitor weight and orthostatics every visit, escalate to jejunal (never gastric) feeding when oral nutrition fails, and refer for G-POEM or gastric electrical stimulation — not intrapyloric botox — when refractory.