Introduction

  • Nausea is a protective mechanism to warn the body of potential toxin ingestion; it may occur with or without emesis.
  • A common presenting complaint in emergency departments.
  • No widely accepted evidence-based guideline to optimize the use of antiemetic medications for N/V in the adult ED setting.
  • A broad list of possible causes; unique etiologies include cannabinoid hyperemesis and hyperemesis gravidarum of pregnancy.
  • Complex pathophysiology involving CNS, ANS, gastric dysrhythmias, and the endocrine system.

Clinical Detail

ParameterOndansetron
(5HT-3)		Metoclopramide
(D2, 5HT-3)		Prochlorperazine
(D2, M1, H1)		Promethazine
(D2, M1, H1)		Haloperidol
(D2)		Droperidol
(D2)
DoseOral, IM, IV: 4-8 mg as a single doseIV: 10-20 mg as a single dose
PO: 10 mg as a single dose		PO: 5-10 mg
IM: 5-10 mg; IV: 2.5-10 mg
PR: 25 mg		Oral, IM, IV, rectal: 12.5-25 mgIV/IM, PO: 0.5-2 mgIV/IM: 1.25-2.5 mg
Administrationvia IV pushIV: ≤10 mg can be given IVP over at least 2 min; give doses >10 mg over at least 10 min
IV: max rate 5mg/min
IV can cause hypotension
Do not give SC		Avoid SubQ formulations due to risk of severe tissue damage (ISMP 2018)
IM = preferred parenteral route		Can give the lactate injectable formulation IM or IV
Consider ECG monitoring prior and during IV administration for high-risk patients		IM, IV via slow IV push administration
Consider ECG monitoring prior and during IV administration for high-risk patients		 
PK/PDOnset: PO ~30 min
Peak: PO: ~2 hrs; ODT: ~1 hr		Onset: PO: 30-60 min; IV: 1-3 min; IM: 10-15 min
Peak: 1-2 hrs		Onset: 30-40 min; IM: 10-20 min; PR: ~60 min
Peak: IV: 30-60 min		Onset: PO, IM: ~20 min; IV: ~5 min
Peak: Oral: ~2.5 h; PR: ~8 hr		Onset: IM: ~28 min; IV: 3-20 min; PO: 60-90 min
Peak: IM: 20 min; IV: ~30 min; PO: 2-6 hrs		Onset:  
Peak: IV/IM: up to 30 min
Adverse EffectsQTc prolongation, HA, constipationQTc prolongation, EPS, diarrhea, somnolenceQTc prolongation, EPSQTc prolongation, EPS, sedation, phlebitisQTc prolongation, EPS, somnolenceQTc prolongation (box warning), EPS, orthostatic hypotension

Evidence

Author, yearDesign / sample sizeIntervention & ComparisonOutcome
April, 2018RCT (n=122)Inhaled isopropyl alcohol + ondansetron PO
Inhaled isopropyl alcohol + placebo PO
Inhaled placebo + ondansetron PO		Mean decrease in nausea VAS score was 30 mm (95% CI 22-37 mm) for group A, 32 mm (95% CI 25-39 mm) for group B, and 9 mm (95% CI 5-14 mm) for group C
No adverse events were reported in either arm
Aromatherapy with or without PO ondansetron provided greater relief than PO ondansetron alone
Meek, 2018RCT (n=215)Efficacy of droperidol (1.25 mg IV) vs ondansetron (8 mg IV) vs 0.9% saline placebo for adult ED nauseaSymptom improvement occurred in 75% (95% CI 64-85%) of droperidol participants, 80% (95% CI 69-89%) for ondansetron, and 76% (95% CI 64-85%) for placebo
Mean VAS score changes were -29 mm (95% CI -36 to -23mm) in droperidol, -34 mm (95% CI -41 to -28 mm) in ondansetron, and -24 mm (95% CI -29 to -19 mm) in placebo
Superiority was not demonstrated for droperidol or ondansetron vs placebo
Parker, 2018Retrospective review (n=35,824)Review of ondansetron use in first-trimester nausea and vomiting of pregnancy and incidence of major birth defectsNo association found with ondansetron use and increased risk of birth defects for most of the 51 defects groups
Modest increase in risk of cleft palate (adjusted OR 1.6, 95% CI 1.1-2.3) observed in NBDPS and renal agenesis-dysgenesis (adjusted OR 1.8, 95% CI 1.1-3.0) observed in BDS (adjusted OR 1.8, 95% CI 1.1-3.0) - though these findings may be due to chance
Culver, 2017RCT (n=133)Ondansetron + IV opioid vs IV opioid to prevent opioid-induced nauseaNo significant difference in nausea 5 min post opioid administration between ondansetron + opioid vs opioid monotherapy (7.2% vs. 12.5%; p=0.308)
No statistical difference in emesis, rescue antiemetic use, or nausea severity between treatment groups
Egerton-Warburton, 2014RCT (n=270)Efficacy of ondansetron (4 mg IV) vs metoclopramide (20 mg IV) vs placebo in nausea and vomiting reduction in the EDMean decrease in VAS score was 27 mm (95% CI 22-33 mm), 28 mm (95% CI 22-34 mm), 23 mm (95% CI 16-30 mm) for ondansetron, metoclopramide, and placebo, respectively
Differences in VAS score reduction of antiemetics vs placebo were not significant
Braude, 2008RCT (n=120)Promethazine (25 mg IV) vs ondansetron (4 mg IV) to treat undifferentiated nausea in the EDSimilar nausea reduction in visual analog scale (VAS) score (difference -2 mm; 95% CI = -13 to 8 mm)
Similar anxiety reduction in both groups (difference -1 mm; 95% CI=-10 to 10 mm)
Promethazine was associated with significantly more sedation than ondansetron (difference 14 mm; 95% CI= 5 to 24mm)

Conclusions

  • Antiemetic agents studied in the ED setting include ondansetron, promethazine, prochlorperazine, metoclopramide, and droperidol.
  • Clinicians should Optimize therapy based on efficacy, side effect profile, patient's preference, and cost in selection of agent.
  • May utilize IV Benadryl for EPS prevention of agents.

References

  • Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved Febuary 1, 2021, from
  • http://www.micromedexsolutions.com/
  • https://pubmed.ncbi.nlm.nih.gov/26411330/
  • https://pubmed.ncbi.nlm.nih.gov/18304050/
  • https://pubmed.ncbi.nlm.nih.gov/29995744/
  • https://pubmed.ncbi.nlm.nih.gov/24818542/
  • https://pubmed.ncbi.nlm.nih.gov/29449262/
  • https://pubmed.ncbi.nlm.nih.gov/29463461/
  • https://pubmed.ncbi.nlm.nih.gov/28987314/
  • https://pubmed.ncbi.nlm.nih.gov/30368981/
Tags:nausea vomiting antiemetics ondansetron