Nausea and Vomiting

Nausea and Vomiting — scientific infographic poster
Anatomical cross-section illustrating organs affected by Nausea and Vomiting
Anatomical cross-section illustrating organs affected by Nausea and Vomiting.
Microscopic view of Nausea and Vomiting cellular pathology
Microscopic view of Nausea and Vomiting cellular pathology.
Medical visualization of Nausea and Vomiting clinical presentation
Medical visualization of Nausea and Vomiting clinical presentation.

Table of Contents

  1. Pathophysiology of Nausea
  2. GI Causes
  3. Metabolic and Medication Causes
  4. Central Nervous System Causes
  5. Cannabinoid Hyperemesis Syndrome
  6. Antiemetic Pharmacology
  7. Acute Workup and Red Flags
  8. Dehydration and Supportive Care
  9. Connections
  10. References & Research
  11. Featured Videos

Pathophysiology of Nausea

Vomiting is coordinated by the dorsal vagal complex (DVC) — specifically the nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus — located in the medulla. The DVC integrates signals from four major input streams to orchestrate the vomiting reflex.

The chemoreceptor trigger zone (CTZ), also called the area postrema, sits on the floor of the fourth ventricle outside the blood-brain barrier (BBB), making it uniquely accessible to blood-borne toxins, drugs, and metabolic products. It expresses dopamine D2, serotonin 5-HT3, neurokinin NK1, and mu-opioid receptors — the pharmacological targets of modern antiemetics.

The vestibular system feeds into the CTZ/NTS via histamine H1 and muscarinic acetylcholine (mACh) receptors, explaining why antihistamines and anticholinergics work for motion sickness. The cerebral cortex generates anticipatory and psychogenic nausea through conditioned responses — seen in chemotherapy patients who become nauseated before treatment begins. Vagal afferents from the GI tract, particularly enterochromaffin cells that release serotonin (5-HT) onto 5-HT3 receptors on vagal nerve endings, carry signals to the NTS — a pathway critical in chemotherapy-induced, gastroenteritis, and gastroparesis-related nausea.

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GI Causes

Gastroenteritis is the most common cause of acute nausea and vomiting worldwide. Viral causes dominate: norovirus produces projectile vomiting with a 24-48-hour illness, requires as few as 1-2 million virions for infection, and spreads rapidly in closed settings such as cruise ships through fecal-oral transmission. Rotavirus is the leading cause in young children (vaccine available). Adenovirus causes milder, more prolonged illness. Bacterial causes include Staphylococcus aureus (preformed toxin — onset 1-6 hours after eating reheated protein foods), Bacillus cereus (similar rapid onset, classically fried rice), Salmonella (8-48 hours, poultry/eggs), and Campylobacter.

Gastroparesis is delayed gastric emptying without mechanical obstruction. The most common systemic cause is diabetic autonomic neuropathy from chronic hyperglycemia. Post-viral and post-surgical vagal injury are other important causes. Symptoms include postprandial nausea, early satiety, and bloating; diagnosis requires nuclear gastric emptying scintigraphy (4-hour study). Treatment options include metoclopramide, domperidone, erythromycin (motilin agonist), and gastric electrical stimulation for refractory cases.

Intestinal obstruction presents with bilious vomiting, colicky pain, and abdominal distension — CT abdomen is required. Peptic ulcer disease causes nausea with meals and epigastric pain, often H. pylori-related. Appendicitis classically begins with anorexia and periumbilical nausea before localizing to the right lower quadrant. Pancreatitis presents with nausea plus severe epigastric pain radiating to the back with lipase more than three times the upper limit of normal. Hepatitis and biliary colic round out common hepatobiliary causes.

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Metabolic and Medication Causes

Medications are the leading cause of chronic nausea. Opioids activate both the CTZ mu-opioid receptors and the vestibular system, causing nausea in 30-40% of patients; ondansetron or transdermal scopolamine are used for prevention. NSAIDs cause direct GI mucosal irritation. SSRIs and SNRIs produce transient nausea in the first 1-2 weeks through 5-HT3-mediated effects in the gut. Digoxin toxicity classically causes nausea with yellow-green halos in vision. Chemotherapy-induced nausea and vomiting (CINV) is categorized by emetogenic risk: highly emetogenic regimens (cisplatin, AC doxorubicin/cyclophosphamide) require prophylaxis with the "triplet" — a 5-HT3 antagonist (ondansetron) plus an NK1 antagonist (aprepitant) plus dexamethasone. Breakthrough CINV is managed with lorazepam or haloperidol. Delayed CINV (days 2-5 post-chemotherapy) is most effectively prevented by NK1 antagonists.

Nausea and vomiting of pregnancy (NVP) — colloquially "morning sickness," though it can occur at any time — affects 70-80% of pregnant women in the first trimester. Human chorionic gonadotropin (hCG) is the primary trigger; nausea severity correlates with hCG levels, which peak around weeks 8-10. Hyperemesis gravidarum (HG) is defined by persistent vomiting, weight loss exceeding 5% of pre-pregnancy body weight, and ketonuria. Treatment escalates through pyridoxine plus doxylamine (Diclegis), ondansetron, and antihistamines; severe cases may require methylprednisolone, NG tube feeding, or TPN.

Metabolic causes include hypercalcemia (part of the "bones, stones, groans, and psychic moans" syndrome — nausea with constipation, from PTH-mediated or malignancy-mediated hypercalcemia), hyponatremia (cerebral edema causes nausea), uremia in CKD stage 5, and Addison's disease (cortisol deficiency causing nausea, anorexia, and weight loss).

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Central Nervous System Causes

Increased intracranial pressure (ICP) causes projectile vomiting that occurs without preceding nausea — a critical distinguishing feature. An intracranial mass, hemorrhage, or acute hydrocephalus can all present this way. Accompanying severe headache (especially "worst of life" suggests subarachnoid hemorrhage), papilledema, and altered consciousness mandate immediate CT head. Migraine produces nausea and vomiting as part of the attack, often accompanied by unilateral headache, photophobia, and phonophobia. A complication specific to migraine is gastroparesis during the headache phase, which impairs oral drug absorption — intravenous or intranasal routes are preferred in the ED. Metoclopramide IV is effective for both the nausea and the headache.

Labyrinthitis and vestibular neuritis produce intense vertigo with prominent nausea and vomiting; vestibular neuritis occurs without hearing loss, labyrinthitis with. Both typically follow upper respiratory infection. The Epley maneuver is effective if a BPPV component is present.

Brainstem strokes, particularly Wallenberg syndrome (lateral medullary syndrome from PICA territory infarction), cause severe nausea with vertigo, dysphagia, ipsilateral facial numbness, and contralateral body numbness. On exam, vertical skew deviation (one eye higher than the other) strongly suggests a central rather than peripheral vestibular cause.

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Cannabinoid Hyperemesis Syndrome (CHS)

CHS is cyclic, severe vomiting in heavy, chronic cannabis users. The hallmark — and effectively pathognomonic feature — is compulsive hot showers or baths that temporarily relieve nausea. The proposed mechanism involves transient receptor potential vanilloid 1 (TRPV1) receptors: heat activates skin and gut TRPV1, generating descending inhibitory signals that override the CTZ. The prodromal phase, lasting months, consists of early morning nausea that responds to cannabis. The hyperemetic phase involves severe vomiting, abdominal pain, and weight loss that only resolves after cannabis cessation.

CHS is frequently misdiagnosed for years during extensive workups. In the ED, haloperidol (5mg IV or IM) shows better evidence than ondansetron, whose 5-HT3 mechanism does not address the underlying CTZ dysregulation. Topical capsaicin cream applied to the abdomen activates TRPV1 desensitization and has growing evidence as an acute treatment. Cannabidiol (CBD) does not cause CHS but cannabis reuse after apparent recovery reliably triggers relapse. Cessation is the only cure.

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Antiemetic Pharmacology

5-HT3 antagonists (ondansetron, granisetron, palonosetron) block serotonin receptors on vagal afferents and in the CTZ. Palonosetron has a longer half-life and is superior for delayed CINV. The class carries a QTc-prolongation risk; a baseline ECG is recommended for high-dose use and the drugs should be avoided when QTc exceeds 470ms.

D2 antagonists include metoclopramide (CTZ blockade plus prokinetic gastroparesis benefit; risk of akathisia and tardive dyskinesia with prolonged use — limit to less than 12 weeks), prochlorperazine (compazine; effective and inexpensive; a go-to in the ED), haloperidol (best evidence for CHS and refractory nausea), and domperidone (no CNS penetration, minimal extrapyramidal side effects; not available in the US; widely used internationally for gastroparesis and nausea in Parkinson's disease).

NK1 antagonists (aprepitant, fosaprepitant IV, netupitant/palonosetron combination Akynzeo) are primary agents for delayed CINV and post-operative nausea. Aprepitant is a substrate and inhibitor of CYP3A4 — check for drug interactions. H1 antihistamines (dimenhydrinate, diphenhydramine, meclizine, promethazine) treat vestibular nausea and motion sickness. Promethazine is potent but sedating; IV promethazine carries a black box warning for tissue necrosis at injection sites and should be given IM or orally. Scopolamine (transdermal patch; 72-hour duration) is the best anticholinergic for motion sickness. Dexamethasone reduces prostaglandins in the gut and synergizes with 5-HT3 and NK1 agents for high-emetogenic chemotherapy. Dronabinol and nabilone (cannabinoids) treat refractory CINV via CB1 receptors. Ginger (1g/day) has modest but safe evidence for pregnancy NVP.

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Acute Workup and Red Flags

Immediate red flags requiring emergency evaluation: hematemesis (vomiting blood — upper endoscopy for varices, Mallory-Weiss tear, or peptic ulcer); feculent vomiting (lower GI obstruction or colovesical fistula — surgical emergency); projectile vomiting without preceding nausea (increased ICP — immediate CT head); severe headache with vomiting (subarachnoid hemorrhage until proven otherwise).

Infants require special consideration: non-bilious projectile vomiting in the first 4 weeks of life suggests pyloric stenosis — a palpable olive-shaped mass in the epigastrium, confirmed by ultrasound, with a classic metabolic picture of hypochloremic hypokalemic metabolic alkalosis. Bilious vomiting in an infant requires urgent evaluation for malrotation with volvulus (surgical emergency).

Standard workup: comprehensive metabolic panel (electrolytes, BUN, creatinine, glucose, liver enzymes, calcium); urinalysis; lipase; pregnancy test (any woman of childbearing age regardless of reported contraception); blood cultures if febrile and ill-appearing; CT abdomen/pelvis when obstruction or surgical cause is suspected.

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Dehydration and Supportive Care

For mild-to-moderate dehydration, oral rehydration therapy (ORT) is preferred. WHO oral rehydration solution (90 mmol/L sodium, 111 mmol/L glucose) is the gold standard. Sports drinks are suboptimal — high glucose, low sodium. Pedialyte is appropriate for children. The BRAT diet and strict clear liquid diet are outdated; current evidence supports early return to a normal, tolerated diet. Administer 5-10 mL every 5 minutes initially to avoid triggering the vomiting reflex.

IV fluids (normal saline preferred; lactated Ringer's for prolonged illness with hyperchloremia risk) are needed for moderate-to-severe dehydration or persistent vomiting. Monitor electrolytes: hyponatremia can result from replacing losses with plain water; hypokalemia develops from persistent vomiting plus metabolic alkalosis (HCl loss from gastric contents). In any patient with prolonged vomiting or malnutrition, administer thiamine before any glucose-containing fluids — Wernicke's encephalopathy is a preventable but potentially fatal complication.

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Connections

References & Research

Historical Background

The neuroanatomy of vomiting was systematically mapped in the 1950s by Borison and Wang, who identified the chemoreceptor trigger zone in the area postrema and established that it lies outside the blood-brain barrier. This distinction between the CTZ and the medullary vomiting center explained why blood-borne toxins could trigger vomiting without crossing into brain tissue, and laid the pharmacological foundation for targeted antiemetics. The 5-HT3 antagonists, introduced in the early 1990s, transformed cancer chemotherapy. NK1 antagonists followed in the 2000s, providing the missing tool for delayed CINV. The recognition of CHS emerged gradually from the early 2000s; the first systematic series was published in 2004.

Key Research Papers

  1. Borison HL, Wang SC. Physiology and pharmacology of vomiting. Pharmacological Reviews. 1953;5(2):193-230.
  2. Singh P, Yoon SS, Kuo B. Nausea: a review of pathophysiology and therapeutics. Therapeutic Advances in Gastroenterology. 2016;9(1):98-112.
  3. Hesketh PJ. Chemotherapy-induced nausea and vomiting. New England Journal of Medicine. 2008;358(23):2482-2494.
  4. ACOG Practice Bulletin No. 153: Nausea and Vomiting of Pregnancy. Obstetrics & Gynecology. 2015;126(3):e12-24.
  5. Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clinic Proceedings. 2012;87(2):114-119.
  6. Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron and the role of serotonin in cisplatin-induced nausea and vomiting. New England Journal of Medicine. 1990;322(12):810-816.
  7. Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L. Clinical guideline: management of gastroparesis. American Journal of Gastroenterology. 2013;108(1):18-37.
  8. Niebyl JR. Nausea and vomiting in pregnancy. New England Journal of Medicine. 2010;363(16):1544-1550.
  9. Quigley EM, Hasler WL, Parkman HP. AGA technical review on nausea and vomiting. Gastroenterology. 2001;120(1):263-286.
  10. Smith LA, Azariah F, Lavender VT, Stoner NS, Bettiol S. Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy. Cochrane Database of Systematic Reviews. 2015;(11):CD009464.
  11. Tan S, De Aquino A. Topical capsaicin for the treatment of cannabinoid hyperemesis syndrome in the emergency department: a retrospective chart review. Journal of Medical Toxicology. 2018;14(3):234-239.
  12. Barnett J, Bhatta A. Wernicke's encephalopathy: causes and management. Practical Neurology. 2019;19(3):206-211.

PubMed Topic Searches

  1. Chemotherapy-induced nausea and vomiting prophylaxis
  2. Hyperemesis gravidarum treatment
  3. Cannabinoid hyperemesis syndrome
  4. Gastroparesis diagnosis and management
  5. Nausea pathophysiology area postrema
  6. Pyloric stenosis infantile vomiting

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