All Pharmacy Pearls

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

Pharmacology of antiemetic agents used for nausea and vomiting in the adult ED — receptor targets, dosing by route, administration considerations, pharmacokinetics, and characteristic adverse effects.

Agent (Receptor)Ondansetron (5-HT3)Metoclopramide (D2, 5-HT3)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
Administration• Via IV push• IV: ≤10 mg can be given IVP over 1–2 min; give doses >10 mg over at least 10 min• IV: max rate 5 mg/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

Overview of the evidence for antiemetic agents studied in the ED setting.

Author, YearDesign / Sample SizeIntervention & ComparisonOutcome
April, 2018RCT (n=122)Inhaled isopropyl alcohol + ondansetron PO vs inhaled isopropyl alcohol + placebo PO vs 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 nausea• Symptom 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 −23 mm) 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 defects• No 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 — though these findings may be due to chance
Culver, 2017RCT (n=133)Ondansetron + IV opioid vs IV opioid to prevent opioid-induced nausea• No 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 ED• Mean decrease in VAS score was 27 mm (95% CI 22–33 mm), 28 mm (95% CI 22–34 mm), and 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 ED• Similar 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 24 mm)

Conclusions

    (Amir Haddad & [email protected]

    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

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