• The use of anti-emetics is ubiquitous in the emergency department (ED) however while many of the commonly used agents have been shown to be effective outside the ED (e.g. post-operative nausea or chemotherapy-induced nausea), there is a relative lack of evidence for their efficacy in an ED population.
• Always consider and treat the cause of the nausea/vomiting.
• Anti-emetics are not benign treatments and their side effects should be considered especially when combining multiple agents.
• Most nausea in the ED is self-limiting.

General Approach to Treatment of Nausea/Emesis in the Emergency Department

• 1st line: Isopropyl Alcohol Swabs
  • In the studies looking at this patients were typically given a few isopropyl alcohol swabs and were instructed to inhale with the swabs 1-2cm under their nose as open as necessary to provide relief from their nausea.
  • Multiple randomized controlled trials (RCTs) show efficacy vs placebo with good safety profile, cost-effective.
• 2nd line: Ondansetron SL/IV 4-8mg q8h
  • There are no good RCTs for ondansetron in the general ED population but there is good evidence outside ED as well as for specific disorder (e.g. paediatric gastroenteritis) and it has a good safety profile.
• 3rd line: Haloperidol PO/IV 0.5-1mg q6h
  • One small RCT showed improvement of nausea with Droperidol in the ED which is pharmacologically similar. It has more side effects in comparison to Ondansetron.
• If none of the above work other medications with little to no evidence in the ED can be considered (e.g. Olanzapine 2.5mg IV/IM) but one should be aware that many of the side effects can be additive (e.g. sedation, QT-prolongation) and multiple failed medications should be an alert to once again consider underlying cause (e.g. small bowel obstruction).
• Dimenhydrinate (50mg PO or IV q4h) deserves a special note as it is one of the most commonly used antiemetics but it has only been shown to be effective for a few specific indications (see below). Conversely, it can cause harm through sedation and increased rates of For these reasons it is likely overutilized in the emergency department for the treatment of nausea.
• Consider tailoring medication based off of specific clinical situation (see below), or to avoid specific side effects (see below).
• While there is no strong evidence that anti-emetics outperform placebo in the ED, it should be noted that this was not due to lack of a positive effect (but rather the placebo also performed well in most of these trials).
• Ensure you investigate and treat any underlying cause (e.g. pain, bowel obstruction).
• Ensure you consider and rule out serious complications of emesis (e.g. esophageal rupture, severe dehydration, etc.)

Situation Specific Approach

Pediatric Gastroenteritis

• 1st line: Ondansetron 4-8mg SL or IV q8h (multiple RCTs showed reduced admissions, decreased use of IV fluids, and decreased rates of emesis).

BPPV

• The best evidence is for Epley’s and Semont Maneuvers (NNT 2-3).
• If a patient is unable to tolerate Epley’s Maneuvers can consider using an antihistamine (e.g. dimenhydrinate 50mg PO or IV q4h).

Other Vertigo

• Antihistamines have been shown to have some benefit (e.g. dimenhydrinate 50mg PO or IV q4h or Betahistine 24mg PO BID).
• Note some experts reserve betahistine for Meniere’s disease but a Cochrane systematic review found evidence (low quality) for use in all comers with vertigo.

Nausea in pregnancy/hyperemesis gravidarum

• 1st line: Pyridoxine-Doxylamine 10mg-10mg PO (Diclectin) – supported by a Cochrane review of 41 trials.
  • Usually already undertaken prior to patients presenting to the ED.
  • Starts at 1 tab PO Maximum 4 tablets daily (1 morning, 1 afternoon, 2 evening).
• 2nd line: H1 antagonist g. Dimenhydrinate 50mg IV.
• 3rd line: Dopamine antagonist g. Metoclopramide 5-10mg PO/IM/IV q6h.
• 4th line: 5-HT3 antagonist g. Ondansetron 4-8mg SL/IV q8h.
• As outpatient consider ginger 250mg QID (one review of 12 RCTs found it effective compared to placebo).

Motion Sickness

• Scopolamine patch (1mg) applied for up to 72h.
• Antihistamines (e.g. dimenhydrinate 50mg PO or IV q4h).

Migraines

• Metoclopramide 5-10mg PO/IM/IV q6h.

 Cyclic Vomiting

• Prophylactic
  • 1st line: Amitriptyline 75-100mg PO daily.
  • 2nd line: Topirimate 100mg PO.
• Abortive
• • 1st line: Sumitriptan intranasal 20mg or subcutaneous 6mg.
  • 2nd line: Aprepitant 125mg PO.
• No good evidence for any of these recommendations are by expert opinion.

Cannabinoid Hyperemesis Syndrome

• Haloperidol 0.05 – 0.1mg/kg IV
  • Best evidence is from the HaVOC trial comparing Haloperidol with Ondansetron which showed Haloperidol as superior.
• Capsaicin Cream 0.075% applied topically q4h
  • Evidence is from 1 small RCT and meta-analyses of 7 retrospective studies which showed symptomatic relief and reduced LOS with use of capsaicin cream.
• Expert recommendation is 6 months OR 3 typical vomiting cycles of abstinence from cannabis.

Prophylaxis of Opioid-Induced Nausea and Vomiting

• No evidence for pre-treatment with an anti-emetic.
• Many of these patients are likely vomiting due to pain, EPs should focus on treating this prior to treating any nausea.

• Dexamethasone 8-12mg PO or 10mg IV (effective in post-operative nausea (PONV) and chemotherapy-induced nausea (CINV), not well studied in the ED).
• Olanzapine 5-10mg PO qdaily or 5mg IV/IM (effective in PONV and CINV, not well studied in the ED).
• Prochlorperazine 10mg PO q6h (evidence in PONV and CINV, no good evidence in the ED).
• Droperidol 2.5mg IV/IM. This is one of the few antiemetics that has some evidence for efficacy in the ED population however it was removed from the market many years ago due to a black box warning on QT prolongation, although there is no evidence that it prolongs QT any more than It has recently returned to the US market but it still isn’t available in Canada.
• NK-1 Receptor Antagonists: g. Aprepitant 125mg PO (shown to be very effective agents in CINV however very expensive and not studied or available in the ED).
• Palonosetron 25mg IV (2nd generation 5-HT3 Antagonist which doesn’t prolong QT. It is approved in Canada but rejected by the BC formulary, likely due to cost).

PONV = Post-Operative Nausea and Vomiting
CINV = Chemotherapy-Induced Nausea and Vomiting

Side Effects/Safety Issues

• Medications with dopamine Antagonism (e.g. haloperidol, droperidol, metoclopramide, promethazine, prochlorperazine).
  • All can cause extrapyramidal side effects (acute dystonia, tardive dyskinesia, etc.)
  • Metoclopramide also causes galactorrhea and anxiety.
  • Contraindicated in Parkinson’s disease and Lewy body dementia.
• Medications with H1 antagonism (e.g. dimenhydrinate, diphenhydramine, promethazine).
  • Cause sedation and can exacerbate delirium.
• Antimuscarinics (e.g. scopolamine).
  • Can cause dry mouth, blurry vision, and sedation.
• Medications 5-HT3 antagonism (e.g. ondansetron, palonosetron, metoclopramide).
  • Can cause headaches, dizziness, and constipation.

Anti-emetics with QT-prolongation

• Antihistamines
• Dopamine antagonists
  • Some sources recommend giving Haloperidol IV over 5 minutes to avoid significant QT prolongation.
• 5-HT3 antagonists (with the exception of palonosetron)
  • Some sources recommend giving ondansetron IV over 15 minutes to avoid significant QT prolongation.
• Cardiac monitoring recommended in high risk patients

1. Furyk, J. S., Meek, R. A., & Egerton-Warburton, D. (2015). Drugs for the treatment of nausea and vomiting in adults in the emergency department setting. Cochrane Database of Systematic Reviews, (9).

   
   

2. DeCamp, L. R., Byerley, J. S., Doshi, N., & Steiner, M. J. (2008). Use of antiemetic agents in acute gastroenteritis: a systematic review and meta-analysis. Archives of pediatrics & adolescent medicine, 162(9), 858-865.

   
   

3. Farkas, J. (2021, November 29). Nausea, emesis, and Antiemetics. EMCrit Project. Retrieved March 24, 2022, from https://emcrit.org/ibcc/antiemetic/

   
   

4. Hilton, M. P., & Pinder, D. K. (2014). The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo. Cochrane database of systematic reviews, (12).

   
   

5. Motamed H, Moezzi M, Rooyfard AD, Angali KA, Izadi Z. A Comparison of the Effects and Side Effects of Oral Betahistine with Injectable Promethazine in the Treatment of Acute Peripheral Vertigo in Emergency. Journal of clinical medicine research. 2017

   
   

6. Murdin, L., Hussain, K., & Schilder, A. G. (2016). Betahistine for symptoms of vertigo. Cochrane Database of Systematic Reviews, (6).

   
   

7. Das, J. K., Kumar, R., Salam, R. A., Freedman, S., & Bhutta, Z. A. (2013). The effect of antiemetics in childhood gastroenteritis. BMC Public Health, 13(3), 1-10.

   
   

8. Athavale, A., Athavale, T., & Roberts, D. M. (2020). Antiemetic drugs: what to prescribe and when. Australian Prescriber, 43(2), 49.

   
   

9. Herrstedt, J. (2018). The latest consensus on antiemetics. Current opinion in oncology, 30(4), 233-239

   
   

10. Flake, Z. A., Scalley, R., & Bailey, A. G. (2004). Practical selection of antiemetics. American family physician, 69(5), 1169-1174.

    
    

11. Hendren, G., Aponte-Feliciano, A., & Kovac, A. (2015). Safety and efficacy of commonly used antiemetics. Expert opinion on drug metabolism & toxicology, 11(11), 1753-1767

    
    

12. Skoetz, N., Haque, M., Weigl, A., Kuhr, K., Monsef, I., Becker, I., & Jordan, K. (2017). Antiemetics for adults for prevention of nausea and vomiting caused by moderately or highly emetogenic chemotherapy: a network meta-analysis. The Cochrane Database of Systematic Reviews, 2017(9).

    
    

13. April, M. D., Oliver, J. J., Davis, W. T., Ong, D., Simon, E. M., Ng, P. C., & Hunter, C. J. (2018). Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: a randomized controlled trial. Annals of emergency medicine, 72(2), 184-193.

    
    

14. Beadle, K. L., Helbling, A. R., Love, S. L., April, M. D., & Hunter, C. J. (2016). Isopropyl alcohol nasal inhalation for nausea in the emergency department: a randomized controlled trial. Annals of Emergency Medicine, 68(1), 1-9.

    
    

15. Sorensen, C. J., DeSanto, K., Borgelt, L., Phillips, K. T., & Monte, A. A. (2017). Cannabinoid hyperemesis syndrome: diagnosis, pathophysiology, and treatment—a systematic review. Journal of Medical Toxicology, 13(1), 71-87.

    
    

16. Venkatesan, T., Levinthal, D. J., Li, B. U., Tarbell, S. E., Adams, K. A., Issenman, R. M., … & Hasler, W. L. (2019). Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterology & Motility, 31, e13606.

    
    

17. Cruz, A., Paloucek, F. P., & Petzel, R. (2020). Topical capsaicin for cannabinoid hyperemesis syndrome. Clinical Toxicology (Philadelphia, Pa.), 58(9), 938-938.

    
    

18. Dida, J., & Walji, N. (2018). BET 1: Haloperidol in cannabinoid hyperemesis syndrome. Emergency Medicine Journal, 35(11), 711-712.

    
    

19. Ruberto, A. J., Sivilotti, M. L., Forrester, S., Hall, A. K., Crawford, F. M., & Day, A. G. (2021). Intravenous haloperidol versus ondansetron for cannabis hyperemesis syndrome (HaVOC): a randomized, controlled trial. Annals of Emergency Medicine, 77(6), 613-619.

    
    

20. Dean, D. J., Sabagha, N., Rose, K., Weiss, A., France, J., Asmar, T., … & Miller, J. (2020). A pilot trial of topical capsaicin cream for treatment of cannabinoid hyperemesis syndrome. Academic Emergency Medicine, 27(11), 1166-1172

    
    

21. Yusuf, H. M., Geier, C., Staidle, A., & Montoy, J. C. C. (2021). Efficacy of topical capsaicin for the treatment of cannabinoid hyperemesis syndrome: A retrospective cohort study. The American Journal of Emergency Medicine, 43, 142-148.

    
    

22. Meek, R., Mee, M. J., Egerton-Warburton, D., Graudins, A., Meyer, A., Pouryahya, P., … & Crow, S. (2019). Randomized Placebo-controlled Trial of Droperidol and Ondansetron for Adult Emergency Department Patients With Nausea. Academic Emergency Medicine, 26(8), 867-877.

    
    

23. 2019 Antiemetic Recommendations for Chemotherapy-Induced Nausea and Vomiting: A Clinical Practice Guideline (Cancer Care Ontario)

    
    

24. Cristofori, F., Thapar, N., Saliakellis, E., Kumaraguru, N., Elawad, M., Kiparissi, F., … & Borrelli, O. (2014). Efficacy of the neurokinin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome. Alimentary pharmacology & therapeutics, 40(3), 309-317.

    
    

25. Viljoen, E., Visser, J., Koen, N., & Musekiwa, A. (2014). A systematic review and meta- analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutrition journal, 13(1), 1-14.

    
    

26. Cyclic Vomiting Syndrome (Li et al. 2021, Uptodate)

    
    

27. Matthews, A., Haas, D. M., O’Mathúna, D. P., & Dowswell, T. (2015). Interventions for nausea and vomiting in early pregnancy. Cochrane Database of Systematic Reviews, (9)

    
    

28. Perisetti A, Gajendran M, Dasari CS, et al. Cannabis hyperemesis syndrome: an update on the pathophysiology and management. Ann Gastroeneterol 2020; 33:571.