NAUSEA AND VOMITING (INCLUDING INTRACTABLE AND REFRACTORY)

Nausea = subjective sensation of impending emesis; vomiting = forceful expulsion of gastric contents — broad differential; antiemetics are symptomatic; identifying and treating the underlying cause is the priority

SYMPTOMS / ASSOCIATED SX

  • Timing: morning (pregnancy, gastroparesis, uremia, alcohol); post-prandial 1–6h (food poisoning, gastroparesis, PUD); >6h after eating (gastric outlet obstruction, gastroparesis)

  • Blood in vomitus: bright red (Mallory-Weiss tear, variceal bleed) or coffee-ground (UGIB — peptic ulcer, erosive gastritis)

  • Associated abdominal pain, fever, diarrhea (infectious/inflammatory); headache, vertigo, diplopia (CNS cause — elevated ICP, posterior fossa)

  • Electrolyte consequences of vomiting: hypokalemia (renal K wasting from metabolic alkalosis), metabolic alkalosis (HCl loss), hypochloremia, hyponatremia

  • Intractable/refractory vomiting: >72h despite standard antiemetics; inability to maintain oral hydration; weight loss; electrolyte derangements; functional impairment

DENIES

  • Hematemesis (UGIB — emergent workup; not simple nausea/vomiting)

  • Projectile vomiting without nausea (elevated ICP, pyloric stenosis — neurologic emergency)

  • Severe abdominal pain (obstruction, pancreatitis, appendicitis — surgical emergency)

  • Pregnancy (urine HCG mandatory in all women of childbearing age BEFORE antiemetics)

  • Prior chemotherapy (CINV — anticipatory, acute, delayed components)

SOCIAL HISTORY

  • Dietary exposures, sick contacts, travel, shellfish/undercooked meat (acute food poisoning)

  • Alcohol use (gastritis, pancreatitis, Mallory-Weiss); pregnancy status; chemotherapy/radiation

  • New medications within past 2 weeks (medication-induced); prior similar episodes (cyclic vomiting, gastroparesis)

  • Psychiatric history, history of eating disorder (rumination syndrome, psychogenic vomiting)

  • CGM/insulin use (DKA); history of DM (gastroparesis)

MAIN ETIOLOGY

  • GI: gastroenteritis (viral — most common acute cause), food poisoning (S. aureus, Bacillus cereus — onset 1–6h after contaminated food), PUD, gastroparesis (DM most common cause; also idiopathic, post-surgical, scleroderma), SBO/LBO, cholecystitis, pancreatitis, hepatitis, appendicitis (early)

  • CNS/vestibular: increased ICP (tumor, hemorrhage, pseudotumor cerebri, meningitis), posterior fossa lesion, vestibular disorders (BPPV, vestibular neuritis, Meniere's), migraine (with or without aura), concussion

  • Metabolic: uremia (BUN-related), DKA/HHS (glucose >250, ketosis), hepatic failure, adrenal insufficiency, hypercalcemia, hypothyroidism, pregnancy-related (hyperemesis gravidarum)

  • Medications (extremely common reversible cause): opioids (direct CTZ stimulation), digoxin (narrow therapeutic index), NSAIDs (gastropathy), antibiotics (especially erythromycin — motilin agonist, metronidazole, tetracyclines), SSRIs (early treatment), chemotherapy (CINV — emetogenic potential by agent), theophylline, iron, metformin

  • Psychogenic/functional: cyclic vomiting syndrome (CVS), functional nausea and vomiting, rumination syndrome, cannabis hyperemesis syndrome (CHS), anxiety-induced nausea

  • Post-operative: post-operative nausea and vomiting (PONV) — risk factors: female sex, non-smoker, history of motion sickness/PONV, opioid use; first 24h post-anesthesia

INTRACTABLE / REFRACTORY VOMITING — SPECIFIC CAUSES

  • Cyclic vomiting syndrome (CVS): stereotyped, predictable episodes of severe vomiting (hours to days) with symptom-free intervals; associated with migraines; may have prodrome; triggers (infections, stress, menses, certain foods); normal endoscopy and imaging; diagnosis of exclusion

  • Cannabis hyperemesis syndrome (CHS): paradoxical vomiting in chronic heavy cannabis users despite cannabis having antiemetic properties; colicky abdominal pain; compulsive hot showers (hallmark — heat reduces nausea); resolves with cannabis cessation

  • Gastroparesis: delayed gastric emptying without mechanical obstruction; post-prandial fullness, bloating, nausea; vomiting of undigested food hours after eating; confirmed by gastric emptying scintigraphy

  • Chemotherapy-induced nausea and vomiting (CINV): acute (0–24h), delayed (24–120h), and anticipatory (<treatment) phases; emetogenicity varies by agent; ondansetron + NK1 antagonist (aprepitant) ± dexamethasone standard prophylaxis

  • Hyperemesis gravidarum: severe pregnancy-induced vomiting; weight loss >5% pre-pregnancy weight; ketonuria; requires IV hydration; thiamine mandatory

  • Post-operative nausea and vomiting (PONV): first 24h after anesthesia; risk score (Apfel score); ondansetron + dexamethasone + scopolamine patch prevention

  • Bowel obstruction: persistent vomiting with obstipation and colicky abdominal pain; bilious vomiting (small bowel); feculent vomiting (large bowel or distal SBO); CT abdomen/pelvis diagnostic

  • Elevated ICP: projectile vomiting without nausea; headache (worse in AM, with Valsalva); papilledema; CT head emergent

MOST COMMON DDX

  • Viral gastroenteritis (community-acquired, sick contacts, self-limited 24–72h, no bloody diarrhea)

  • Medication-induced (temporal relationship to new medication — onset typically within days to weeks)

  • Gastroparesis (post-prandial vomiting of undigested food, DM or post-surgical history, gastric emptying scan confirms)

  • DKA (glucose >250, AG metabolic acidosis, ketonemia; polyuria, polydipsia history)

  • SBO (colicky pain, obstipation, bilious vomiting, dilated loops on CT)

  • Pancreatitis (epigastric pain radiating to back; lipase >3× ULN; alcohol or gallstone history)

  • Cholecystitis (RUQ pain, fever, Murphy's sign; RUQ ultrasound)

  • Elevated ICP (projectile vomiting without nausea, headache, papilledema; CT head)

  • Pregnancy (urine/serum HCG — ALWAYS check in women of childbearing age)

  • CVS/CHS (history of stereotyped episodes; cannabis use; hot shower behavior)

DATA

  • Urine HCG — MANDATORY in all women of childbearing age BEFORE any antiemetic

  • BMP (electrolytes — hypokalemia, metabolic alkalosis, hypochloremia from vomiting; BUN/Cr — dehydration, renal failure)

  • CBC (leukocytosis — infection/inflammatory; anemia)

  • LFTs; lipase (hepatobiliary, pancreatic)

  • Glucose (DKA, HHS, hypoglycemia-induced nausea)

  • HbA1c (if DM and gastroparesis suspected)

  • Serum ketones/BHB (DKA)

  • Urine ketones and specific gravity (dehydration, DKA)

  • Abdominal XR (free air, dilated bowel loops, air-fluid levels — obstruction; stool burden)

  • CT abdomen/pelvis with contrast (obstruction, pancreatitis, cholecystitis, appendicitis, mesenteric pathology — preferred for persistent/unexplained vomiting)

  • RUQ ultrasound (cholecystitis, biliary pathology — first-line if RUQ pain or jaundice)

  • CT head (elevated ICP, posterior fossa lesion, hemorrhage — if headache, neurologic symptoms, or projectile vomiting)

  • MRI brain (posterior fossa — if posterior stroke or central cause suspected)

  • Gastric emptying scintigraphy (gastroparesis diagnosis — 4h solid meal study; >60% retention at 2h or >10% at 4h = diagnostic)

  • Digoxin level (if on digoxin)

  • Thyroid function tests (TSH) if hypothyroidism suspected

  • Ammonia, LFTs (hepatic failure)

  • Cortisol, ACTH stim (adrenal insufficiency)

  • Upper endoscopy (EGD): if hematemesis, suspected obstruction, or refractory vomiting without diagnosis — identifies PUD, gastritis, malignancy, bezoar, outlet obstruction

  • Serum calcium, Phos (hypercalcemia-induced vomiting)

  • Urine/serum tox screen (overdose, CHS — cannabis metabolites in urine)

HOME MEDS

  • Opioids — reduce dose or rotate to lower-nauseating agent; naloxone if toxicity suspected

  • Digoxin — check level; hold if toxicity; narrow therapeutic index; nausea is classic toxicity sign

  • NSAIDs — hold (gastropathy, worsens GI irritation)

  • Antibiotics (erythromycin, metronidazole, tetracyclines) — switch if medication-induced

  • Metformin — GI intolerance; switch to extended-release formulation or reduce dose; hold if AKI

  • Iron supplements — take with food; switch to liquid iron or alternative formulation

  • SSRIs — may cause nausea early in treatment (weeks 1–4); take with food; reassure; dose reduction rarely needed

PLAN

INITIAL MANAGEMENT (ALL PATIENTS):

  • NPO if active vomiting or surgical pathology suspected; advance to clear liquids once controlled

  • IV access; IV fluids if unable to maintain oral hydration (dehydrated, persistent vomiting): NS 0.9% or LR 500 mL–1 L IV bolus; reassess; target UO 0.5–1 mL/kg/h

  • Correct electrolytes: K (replace IV if <3.0 or PO if 3.0–3.5 tolerating), Mg (hypoMg impairs K repletion), metabolic alkalosis (correct volume + K → kidney corrects alkalosis)

  • Treat underlying cause (DKA, pancreatitis, cholecystitis, obstruction, meningitis — see respective cards)

ANTIEMETIC LADDER — FIRST-LINE TO REFRACTORY:

  • First-line (start here for most patients):

    • Ondansetron (Zofran) 4–8 mg IV/PO q6–8h PRN (5-HT3 antagonist; most commonly used; monitor QTc; safe in pregnancy — Category B; IV form preferred for active vomiting)

    • Prochlorperazine (Compazine) 5–10 mg IV/PO q6–8h (dopamine D2 antagonist; effective for nausea from various causes; extrapyramidal side effects; avoid in DLB/Parkinson's; give diphenhydramine 25 mg IV prophylactically to prevent akathisia)

    • Promethazine (Phenergan) 12.5–25 mg IV/IM/PO/PR q4–6h (H1 + D2 antagonist; use slow IV infusion — IV push risk of tissue necrosis if extravasated, respiratory depression; extrapyramidal effects; avoid in Parkinson's, DLB, elderly)

    • Metoclopramide 10 mg IV/PO q6h (D2 antagonist + prokinetic — increases LES tone and gastric emptying; useful for gastroparesis; avoid long-term >12 weeks — irreversible tardive dyskinesia — FDA black box warning)

  • Add-on agents:

    • Lorazepam (Ativan) 0.5–1 mg IV/PO q4–6h PRN (benzodiazepine; anxiolytic-antiemetic; useful as adjunct for anticipatory CINV, refractory nausea, anxiety-driven nausea; sedating — use cautiously in elderly)

    • Dexamethasone 4–8 mg IV q6–8h (steroid; adjunct antiemetic especially for CINV, post-operative; enhances efficacy of 5-HT3 antagonists; avoid prolonged use)

    • Haloperidol 0.5–2 mg IV/PO/SQ q6–8h (D2 antagonist; off-label antiemetic; useful for refractory nausea, palliative care, opioid-induced nausea; monitor QTc)

    • Droperidol 0.625–1.25 mg IV/IM (potent D2 antagonist; rapid-acting; highly effective for refractory N/V; FDA black box for QT prolongation — requires ECG and QTc monitoring; effective in small doses)

  • For specific causes:

    • Scopolamine patch 1.5 mg TD q72h (muscarinic antagonist; motion sickness, vestibular nausea, PONV; anticholinergic side effects — dry mouth, blurred vision; avoid in elderly)

    • Meclizine 12.5–25 mg PO q6–8h (H1 antagonist; vestibular nausea, motion sickness; sedating; less effective for non-vestibular causes)

    • Hyoscine butylbromide (Buscopan) 10–20 mg IV/PO q6–8h (anticholinergic antispasmodic; for colicky abdominal pain + nausea from bowel spasm/obstruction — partial obstruction management)

  • INTRACTABLE/REFRACTORY VOMITING (≥72h or failing ≥2 antiemetics):

    • Ensure adequate IV hydration and electrolyte correction ongoing

    • Consider NG tube placement for gastric decompression (especially if obstruction, severe gastroparesis, or inability to tolerate medications)

    • Try combination antiemetic approach: different receptor targets simultaneously (e.g., ondansetron + haloperidol + lorazepam ± dexamethasone)

    • Aprepitant (Emend) 125 mg PO day 1 then 80 mg PO days 2–3 (NK1 receptor antagonist; blocks substance P pathway; highly effective for CINV and refractory nausea from any cause; also available as IV fosaprepitant 150 mg IV × 1 dose; increasingly used for non-CINV refractory nausea)

    • Olanzapine (Zyprexa) 2.5–5 mg PO/SL/IM q6–12h (5-HT3 + D2 + H1 + M antagonist; broad-spectrum antiemetic; very effective for refractory and CINV-related nausea; sedating; monitor glucose especially in diabetics; increasingly used in palliative care and oncology)

    • Trimethobenzamide (Tigan) 300 mg PO TID (D2 antagonist; older agent; alternative in mild-moderate refractory cases)

    • TPN (total parenteral nutrition): consider if enteral route not feasible for >7–10 days or significant malnutrition developing; GI + nutrition team involvement

  • GASTROPARESIS-SPECIFIC (see above for general; add):

    • Erythromycin 3 mg/kg IV q6h (motilin receptor agonist — prokinetic; effective bridge but tolerance develops in 48–72h; use short-term only)

    • Low-fat, low-fiber diet; small-volume frequent meals (6–8/day); avoid carbonated beverages

    • Liquid or semi-liquid meals (empty faster than solids); avoid high-fat foods (delay gastric emptying)

    • Gastric electrical stimulation (GES — Enterra device): severe refractory gastroparesis; reduces vomiting frequency; requires surgical implantation; GI/surgery referral

    • Pyloromyotomy (endoscopic — G-POEM or laparoscopic): newer intervention for refractory gastroparesis; gastroparesis specialist referral

  • CYCLIC VOMITING SYNDROME (CVS):

    • Acute episode: ondansetron 8 mg IV/PO + lorazepam 1–2 mg IV/PO (sedation helps abort episodes); sumatriptan 6 mg SC if migraine-associated; aggressive IVF; dark quiet room (migraine management)

    • Supportive: diphenhydramine 25 mg IV for akathisia; ketorolac 30 mg IV for pain; consider IV haloperidol for severe refractory episodes

    • Prophylaxis (to prevent future episodes): amitriptyline 25–75 mg PO qhs (first-line preventive; also treats underlying migraine); or topiramate 25–100 mg PO daily; or propranolol 10–40 mg PO TID; refer to GI or neurology specialist

    • Avoid triggers: infections, stress, menses, certain foods; sleep hygiene

  • CANNABIS HYPEREMESIS SYNDROME (CHS):

    • Diagnosis: confirm with cannabis use history + compulsive hot bathing behavior (pathognomonic)

    • Acute: haloperidol 5 mg IM (most effective agent for CHS — significantly superior to ondansetron and metoclopramide per multiple studies); or droperidol 2.5 mg IM/IV (effective; monitor QTc)

    • Topical capsaicin cream 0.025–0.075% applied to abdomen (activates TRPV1 receptors; highly effective for CHS; mechanism related to depletion of substance P; apply q4–6h PRN)

    • Hot shower/bath: symptomatic relief only — use sparingly to prevent burns; does not treat underlying pathology

    • Definitive treatment: CANNABIS CESSATION — symptoms resolve completely within days to weeks after stopping; no antiemetic resolves CHS without cessation

    • Counseling and addiction referral; educate patient that cannabis CAUSES the vomiting (paradox); validate without dismissing

  • CHEMOTHERAPY-INDUCED N/V (CINV):

    • Acute (0–24h) prevention: ondansetron 8 mg IV/PO + dexamethasone 12 mg IV + aprepitant 125 mg PO (if high/moderate emetogenicity regimen)

    • Delayed (24–120h) prevention: aprepitant 80 mg PO days 2–3 + dexamethasone 8 mg PO daily

    • Breakthrough CINV: olanzapine 10 mg PO qhs × 3 days (MASCC guidelines; highly effective); or add lorazepam; or switch antiemetic class

    • Anticipatory CINV (before chemotherapy infusion): lorazepam 0.5–1 mg PO night before + morning of; behavioral therapy (systematic desensitization)

    • Refractory CINV: olanzapine + aprepitant + ondansetron + dexamethasone combination; oncology/palliative care consultation

  • HYPEREMESIS GRAVIDARUM:

    • Vitamin B6 (pyridoxine) 10–25 mg PO TID (first-line in pregnancy; safe; modest efficacy)

    • Doxylamine 12.5–25 mg PO BID–TID (antihistamine; Diclegis = pyridoxine + doxylamine — FDA-approved for N/V of pregnancy)

    • Ondansetron 4–8 mg IV/PO q6–8h (safe in pregnancy Category B; avoid first trimester if possible — limited cleft palate association data; use when benefit outweighs risk)

    • IV hydration: NS or LR with D5 once urine ketones resolving; thiamine 100 mg IV before dextrose (Wernicke's risk in hyperemesis)

    • Metoclopramide 10 mg IV/PO q6h (safe in pregnancy)

    • Promethazine 12.5–25 mg IV/IM q4–6h (safe but sedating; use only if above fail)

    • Corticosteroids (methylprednisolone 16 mg PO/IV TID × 3 days then taper): reserve for severe refractory hyperemesis; avoid first 10 weeks (oral cleft risk)

    • Total parenteral nutrition (TPN): only for severe cases with inability to maintain nutrition; GI/OB/nutrition team

    • OB consultation for all cases of hyperemesis gravidarum requiring IV hydration

  • PONV (post-operative nausea and vomiting):

    • Ondansetron 4 mg IV at end of surgery + dexamethasone 4–8 mg IV at induction (combination reduces PONV significantly)

    • Scopolamine patch applied night before surgery (high-risk patients)

    • Haloperidol 0.5–1 mg IM/IV perioperatively (low-dose effective for PONV prevention)

    • Total IV anesthesia (TIVA with propofol) instead of volatile agents reduces PONV in high-risk patients

  • PALLIATIVE/END-OF-LIFE NAUSEA:

    • Identify reversible cause (opioid-induced, hypercalcemia, bowel obstruction, constipation, uremia)

    • Haloperidol 0.5–2 mg SQ/IV q4–6h PRN (first-line for opioid-induced nausea in palliative care; central D2 blockade)

    • Methotrimeprazine (levomepromazine) 6.25 mg SQ q4–8h (broad antiemetic + analgesic + anxiolytic; popular in palliative setting)

    • Octreotide 100–200 mcg SQ TID (for malignant bowel obstruction — reduces GI secretions; reduces vomiting without surgery)

    • Dexamethasone 4–8 mg PO/SQ daily (reduces peritumor edema; reduces N/V from CNS or abdominal malignancy)

    • Palliative care consultation for complex refractory nausea in serious illness

  • TREND: daily weight; strict I&Os; electrolytes (BMP) q24h during active vomiting; renal function; urine ketones; reassess antiemetic regimen response at 24–48h

DISCHARGE:

  • Ensure oral hydration adequate (≥1.5–2 L/day) before discharge; advance diet tolerated

  • Oral antiemetics for discharge: ondansetron 4 mg PO q8h PRN × 3–5 days (most common); or prochlorperazine 5–10 mg PO q6–8h PRN; or promethazine 12.5 mg PO q4–6h PRN (cautiously — sedating; falls risk in elderly)

  • Clear dietary instructions: small frequent meals; avoid triggers; bland foods initially

  • Gastroparesis: low-fat low-fiber diet; small frequent meals; written dietary handout; GI follow-up

  • CVS: prophylactic therapy prescription (amitriptyline or topiramate); trigger avoidance counseling; neurology or GI follow-up

  • CHS: cannabis cessation counseling; addiction medicine referral; document in chart; strict return precautions if cannot stop

  • CINV: antiemetic regimen optimized before next cycle; oncology follow-up coordinated

  • PCP follow-up 1 week for persistent or unexplained nausea; GI referral for refractory cases, gastroparesis, or unexplained chronic nausea

RED FLAGS

  • Hematemesis → emergent EGD; IV PPI (esomeprazole 80 mg IV bolus then 8 mg/h infusion); resuscitation; GI consult

  • Projectile vomiting without nausea + headache + papilledema → elevated ICP emergency; CT head; neurology/neurosurgery

  • Obstruction signs (dilated bowel, obstipation, bilious or feculent vomiting) → CT abdomen; surgery consult; NGT decompression

  • Hyperemesis gravidarum + AMS → Wernicke's risk; thiamine 100 mg IV BEFORE any dextrose

  • Severe dehydration + electrolyte crisis (K <2.5, metabolic alkalosis pH >7.55) → aggressive IV correction; ICU consideration

  • DKA presenting as nausea/vomiting → check glucose and BHB in ALL diabetic patients with unexplained vomiting

  • Vomiting in post-op patient day 3–5 → consider anastomotic leak, ileus, early SBO; CT abdomen; surgery consult

  • Suspected meningitis presenting with vomiting + headache + fever → emergent LP (after CT); IV antibiotics + acyclovir immediately

  • Olanzapine + diabetes: monitor glucose closely — can cause acute hyperglycemia and unmask DKA

SENIOR IM RESIDENT PEARLS

  • ALWAYS check urine HCG in women of childbearing age before ANY antiemetic — pregnancy changes management completely; ondansetron (Category B) vs. promethazine (Category C) vs. metoclopramide

  • Haloperidol is the most effective antiemetic for CHS and for refractory opioid-induced nausea — outperforms ondansetron in multiple CHS studies; use 5 mg IM for acute CHS in the ED/inpatient setting

  • Topical capsaicin to the abdomen is a highly effective CHS treatment — activates TRPV1 receptors and depletes substance P; effective, cheap, and underused; educate on application technique

  • Common mistake: treating CHS with ondansetron — minimally effective; the definitive treatment is cannabis cessation, which must be clearly communicated to the patient

  • Metoclopramide long-term use (>12 weeks) causes irreversible tardive dyskinesia — FDA black box warning; always limit to short-term use and document reason and expected duration

  • NK1 antagonists (aprepitant, fosaprepitant) are highly effective for refractory nausea from any cause — not just chemotherapy; increasingly used for post-operative, cyclic vomiting, and refractory inpatient nausea

  • Common mistake: giving promethazine IV push — severe tissue necrosis if extravasated; risk of respiratory depression; always dilute and give via slow IV infusion over 10–15 min, or use IM route; consider switching to ondansetron

  • Olanzapine is one of the most underused antiemetics in the inpatient setting — broad receptor blockade (D2, 5-HT3, H1, M) makes it highly effective for refractory nausea; start at 2.5 mg in elderly; 5–10 mg in others; sedation is often a side benefit in miserable patients

  • Common mistake: not considering DKA in a diabetic patient presenting with nausea and vomiting — check glucose and BHB in all diabetic patients; euglycemic DKA (SGLT-2 inhibitors) has normal glucose but positive ketones