Background:  Nausea and vomiting (N&V) are distinct but usually overlapping symptoms which impact quality and quantity of life for patients with serious illness (1).  The array of available anti-emetics can make it difficult to determine the best management approach. This Fast Fact offers a framework for identifying common causes and for targeting anti-emetic management.

Definitions: It is important to determine if the patient is experiencing nausea, vomiting, or both, as patients may vomit without preceding nausea or experience nausea without vomiting. Nausea is an unpleasant feeling causing the desire to vomit (2). Vomiting is the contraction of abdominal and diaphragmatic muscles triggering the expulsion of stomach contents (3). 

Common etiologies of N&V in patients with serious illness (4-8):

• Malignant bowel obstruction (MBO): See Fast Facts #45 and 119 for more specifics.
• Infections: generalized (sepsis, pneumonia, coronavirus) or more localized infectious processes (viral gastroenteritis, cholecystitis, bacterial peritonitis, clostridium difficile).  
• Medications: Effects on the chemoreceptor trigger zone (CTZ) or sampling port near the blood brain barrier are thought to be the primary etiology. Collaborate with a pharmacist to examine medications and supplements for emetogenic agents. Common culprits: a) antibiotics; b) opioid-induced nausea (OIN); c) chemotherapy induced nausea and vomiting (CINV); d) antidepressants. 
• Intracranial issues (e.g., brain metastases, increase in intracranial pressure, subarachnoid hemorrhage): address the underlying cause as feasible. Dexamethasone may be beneficial.
• Vestibular: when vertigo is present, patients typically describe an experience of the room spinning without much prompting from the clinician. Benign positional vertigo, vestibulitis, and Schwannomas are common vestibular etiologies for N&V.
• Other causes or factors: post-operative nausea and vomiting (PONV), dehydration, migraine, pregnancy, cannabis hyperemesis syndrome, food poisoning. 
• Of note, constipation, anxiety, or emotional distress may compound N&V of any cause.  

If no obvious cause, or if symptoms ongoing, some experts recommend the following approach based on anecdotal experience (4-5):

• If predominantly nausea, consider a trial of an antidopaminergic medication.
• If predominantly vomiting, consider trial of 5HT3 antagonist such as ondansetron. 
• If symptoms are refractory, consider a different medication class and/or additional workup.

Anti-emetic Groups for N&V (4-9). Asterisk (*) indicates a risk for QTc prolongation.

Group 1: Antidopaminergics (D2 antagonists): recommended for nausea related to medications (e.g., OIN) and other perceived toxins including PONV and CINV.  Acute motor symptoms such as dystonic reactions are possible.  Three categories of antidopaminergics have been described:

• 1A — more potent and longer acting: examples include haloperidol* (though IV formulations maybe less likely to prolong QTc than oral formulations), olanzapine (see Fast Fact #315), chlorpromazine (not a first-line agent per many experts due to risk of sedation). There is little evidence to titrate beyond the recommended dose of haloperidol (1-2 mg/day) and olanzapine (10 mg per day). Controlled data support the use of olanzapine both for CINV and cancer related nausea and vomiting.  
• 1B –weaker/shorter acting:  examples include prochlorperazine*, trimethobenzamide.  
• 1C: Promotility: in addition to antidopaminergic effects, metoclopramide* is a promotility agent for gastroparesis. Use of metoclopramide for 3 months or more is associated with a risk for tardive dyskinesia, particularly in patients with renal/hepatic impairment, diabetes, or who are older than 70.

Group 2: 5HT3 Antagonists:  Ondansetron* is the most prescribed antiemetic in this group.  Beyond their role for CINV, they are preferred anti-emetic options in patients with Parkinson’s, Lewy Body Dementia, or restless leg syndrome, because of lack of effects on the dopamine receptor. 

Group 3: Antihistamines and Anticholinergics: Antihistamines with anti-emetic properties include promethazine*, meclizine, diphenhydramine*. Scopolamine is an anticholinergic with anti-emetic properties. Group 3 anti-emetics are most utilized for vertigo-related nausea.  While they are commonly prescribed for other types of nausea (e.g., scopolamine to reduce GI secretions from an MBO), they should be used with caution in elderly populations due to their risk for delirium.  Parenteral promethazine and diphenhydramine have been associated with misuse from temporary euphoric feelings caution.  Of note, promethazine and prochlorperazine (an antidopaminergic) are very different drugs.

Group 4: Miscellaneous 

• NK1 antagonists (e.g., arepiptant): primarily used for CINV due to cost and administration issues. 
• Dexamethasone has been described as an anti-emetic for CINV, MBO, PONV, and increased intracranial pressure. 
• Cannabinoids: prescription agents such as dronabinol (FDA approved for PONV and CINV) and nabilone (FDA approved for CINV) have shown effectiveness in some published trials.  Cannabis might provide benefit but needs further research. See Fast Facts #93, 279, & 370. 
• Inhaled isopropyl alcohol:  controlled trials suggest effectiveness for PONV and gastroenteritis (9-12).
• Ginger: systematic reviews have shown anti-emetic effect over placebo for PONV and pregnancy (12,13). There are insufficient data regarding its role for CINV and other types of nausea (15).
• Lorazepam: antiemetic role is limited to anticipatory nausea and vomiting (anxiety) (16).

References

1. Hassan BA, Yusof ZB.  Negative impact of chemotherapy on breast cancer patients quality of life – utility of antiemetic treatment guidelines and the role of race
2. Camp-Sorrell D.  Chemotherapy toxicities and management. F.M.H. Yarbro Ed, Cancer Nursing: Principles and Practice (6^thEd), Jones and Bartlett Publishers, Sudbury MA 2005:425-426.
3. Baker PD, Morzorati SL, Ellett ML.  The pathophysiology of chemotherapy-induced nausea and vomiting. Gastroenterol Nurs 2005; 28(6):469-480.
4. Glare, Paul, et al. “Treating nausea and vomiting in palliative care: a review.” Clinical interventions in aging 6 (2011): 243.
5. Becker, Daniel E. “Nausea, vomiting, and hiccups: a review of mechanisms and treatment.” Anesthesia progress 57.4 (2010): 150-157.
6. Saudemont G, Prod’Homme C, Da Silva A, et al. The use of olanzapine as an antiemetic in palliative medicine: a systematic review of the literature. BMC Palliat Care. 2020;19(1):56. Published 2020 Apr 22. doi:10.1186/s12904-020-00559-4
7. Hocking CM, Kichenadasse G.  Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review.  Support Care Cancer 2014; 22:1143-1151.
8. Navari, Rudolph M. “Managing nausea and vomiting in patients with cancer: what works.” Oncology 32.3 (2018).
9. Beadle KL, Helbling AR, et al.  Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial.  Annals of Emergency Medicine 2016; 68(1):1-9,e1.
10. April MD, Oliver JJ, Davis WT, Ong D, Simon EM, Ng PC, et al. Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: a randomized controlled trial. Ann Emerg Med 2018; 72(2):184-193.
11. Pellegrini J, DeLoge LTJ, et al.  Comparison of inhalation of isopropyl alcohol vs promethazine in the treatment of postoperative nausea and vomiting (PONV) in patients identified as at high risk for developing PONV. AANA Journal 2009; 77(4):293-299
12. Verma DK, Bansa S, et al.  Control of postoperative nausea and vomiting in oral and maxillofacial surgery patients with isopropyl alcohol: a prospective randomized controlled trial.  Journal of Maxillofacial and Oral Surgery 2018; 17:576-581.
13. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, Leeprakobboon K, Leelasettagool C. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a meta-analysis. Am J Obstet Gynecol. 2006;194:95–9.
14. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003;(4):CD000145.
15. Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth. 2000;84:367–71.
16. Aapro MS, Molassiotis A, Olver I.  Anticipatory nausea and vomiting.  Support Care in Cancer 2005; 13:117-121.

Version History:  This Fast Fact was originally edited by David E Weissman MD.  2^nd Edition published July 2005; 3^rd Edition May 2015. In September 2021 it underwent a substantial update by Andrew Kammell MD and Sean Marks MD.