Anti-Emetic Tool Box

ICU Anti‑Emetic Toolbox

1. Dopamine‑2 Antagonists / Pro‑kinetics

Agent	Typical ICU Dose	Pearls & ICU Cautions
Metoclopramide	5–10 mg IV q6 h	Anti‑emetic & pro‑kinetic; risk of akathisia/dystonia; ↓dose if CrCl < 40 mL/min
Haloperidol	1–2 mg IV q4–6 h PRN	Useful when agitation co‑exists; monitor QTc
Droperidol	0.625–1.25 mg IV ×1 (may repeat ×1)	Rapid onset; torsades risk—use with continuous ECG
Prochlorperazine	5–10 mg IV q6 h	Potent; EPS common—consider diphenhydramine cover

2. 5‑HT₃ (Serotonin) Receptor Antagonists

Agent	Typical ICU Dose	Pearls & ICU Cautions
Ondansetron	4 mg IV q6 h PRN (up to 8 mg)	Minimal sedation; mild QT prolongation; limit dose in severe hepatic impairment
Granisetron	1 mg IV q12 h	Longer half‑life than ondansetron; option for refractory cases

3. Antihistamine / Anticholinergic

Agent	Typical ICU Dose	Pearls & ICU Cautions
Diphenhydramine	25–50 mg IV q6 h PRN	Helpful for vestibular or medication‑induced NV; sedation & anticholinergic delirium in elderly
Promethazine	12.5–25 mg IV q6 h (slow, diluted)	Potent; vesicant—use large IV line; hypotension and sedation common
Scopolamine patch	1 patch q72 h	Great for vestibular & opioid taper NV; mydriasis—avoid in narrow‑angle glaucoma

Practical ICU Tips

• Start with the likely mechanism: gastroparesis → metoclopramide; opioid withdrawal → haloperidol; vestibular → diphenhydramine.
• Watch the ECG: Many agents prolong QT; obtain baseline & 2–4 h post‑dose ECG when stacking risks.
• Use combination therapy (e.g., 5‑HT₃ + dexamethasone + haloperidol) for refractory cases.
• Adjust for organ dysfunction: reduce metoclopramide in renal failure; limit ondansetron in severe hepatic disease.
• Route matters: IV or transdermal if bowel not functioning; consider NG/OG formulations for long‑term ventilation.
• Re‑evaluate daily: Persistent NV may signal underlying pathology—treat the cause, not just the symptom.

4. Neurokinin‑1 (NK₁) Receptor Antagonists

Agent	Typical ICU Dose	Pearls & ICU Cautions
Fosaprepitant	150 mg IV ×1 (24 h coverage)	Synergistic with 5‑HT3 blockers & steroids; CYP interactions (warfarin, tacrolimus)

5. Corticosteroid

Agent	Typical ICU Dose	Pearls & ICU Cautions
Dexamethasone	4–8 mg IV ×1–2 day	Adjunct for peri‑op, ↑ICP, bowel‑wall edema; onset 2–4 h; monitor glucose/WBC

6. Atypical Antipsychotic

Agent	Typical ICU Dose	Pearls & ICU Cautions
Olanzapine	2.5–5 mg PO/ODT/NG q12–24 h	Refractory chemo‑induced & multifactorial NV; sedation & hypotension; monitor QT

7. Adjunct / Special‑Situation Agents

Situation	Useful Agent(s)	Rationale
Severe gastroparesis / ileus	Erythromycin 250 mg IV q6 h	Short‑term pro‑kinetic; tachyphylaxis in 48–72 h; QT risk
Migraine‑associated NV	IV prochlorperazine ± diphenhydramine	Targets dopaminergic pathway; add IV fluids & magnesium
Cannabinoid hyperemesis	Haloperidol or droperidol	Superior symptom control vs ondansetron in studies
Anxiety‑triggered NV	Lorazepam 0.5–1 mg IV q4 h PRN	Combine with primary anti‑emetic; avoid oversedation

Quick First‑Line Cheat Sheet

Scenario	Go‑to First Dose
Undifferentiated ICU NV	Ondansetron 4 mg IV
Gastroparesis / tube‑feed intolerance	Metoclopramide 10 mg IV
Post‑op NV resistant to ondansetron	Droperidol 0.625 mg IV
Opioid‑exposed, agitated	Haloperidol 1 mg IV
Refractory / high emetogenic chemo	Fosaprepitant 150 mg IV + Ondansetron 8 mg IV + Dexamethasone 8 mg IV

Cannabinoids as Anti‑Emetics

Cannabinoid agonists activate CB₁ receptors in the brainstem vomiting center and enteric plexus, dampening both nausea perception and the motor drive to vomit. They pre‑date modern 5‑HT₃/NK₁ regimens and remain a fallback when standard agents fail—particularly in highly emetogenic chemotherapy or stubborn, multifactorial nausea.

FDA‑Approved Products (United States)

Product (brand)	Formulation / Schedule	Usual Anti‑Emetic Dose*	Approved Indication†	Practical ICU / Bedside Notes
Dronabinol (Marinol®)	2.5 / 5 / 10 mg oral capsules Schedule III	5 mg/m2 PO 1–3 h before chemo; then q2‑4 h × 4–6 doses/day (max 15 mg/m2/day)	CINV after failure of conventional anti‑emetics; AIDS‑related anorexia	Swallow intact; onset 30–60 min—better for prophylaxis. Capsule can be opened for NG administration if needed.
Dronabinol (Syndros®)	5 mg/mL oral solution Schedule II	Same mg/m2 schedule as capsules (administer with calibrated oral syringe)	Same as Marinol®	Faster absorption; alcohol‑containing vehicle—caution with hepatic impairment or disulfiram use.
Nabilone (Cesamet®)	1 mg capsules Schedule II	1–2 mg PO BID; start 1–3 h before chemo, continue BID ≤ 48 h after last dose	CINV refractory to standard therapy	Longer half‑life than dronabinol; no renal adjustment; chiefly hepatic metabolism.

*Adult dosing—titrate to lowest effective dose to limit CNS effects.
†All require prior failure of first‑line anti‑emetics per FDA labeling.

Preparations Not FDA‑Approved for NV

• Nabiximols (Sativex®): 1:1 THC:CBD oromucosal spray approved in Canada/UK for MS spasticity; small trials suggest CINV benefit but not FDA‑approved.
• Whole‑plant medical cannabis: Inhaled or edible forms legal in some U.S. states; THC/CBD ratio and bioavailability vary—not advised in critical‑care settings.

Practical ICU Considerations

1. Reserve for refractory cases – Current NCCN/ASCO algorithms place cannabinoids after failure of 5‑HT₃ + dexamethasone ± NK₁ ± olanzapine.
2. Route limitations – All FDA‑approved products are oral; require functioning GI tract or enteral tube.
3. Adverse effects – Euphoria/dysphoria, sedation, tachycardia, orthostatic hypotension, potential delirium; start low, reassess frequently.
4. Drug interactions – CYP2C9/3A4 substrates; monitor when co‑administered with azoles, macrolides, ritonavir, warfarin, tacrolimus.
5. Legal & storage considerations – Controlled‑substance handling: Schedule II (Cesamet, Syndros) vs Schedule III (Marinol); observe unit storage policies.

Bottom line: Synthetic cannabinoid agents offer a legally sanctioned, evidence‑based fallback for chemotherapy‑related nausea unresponsive to modern first‑line regimens. In the ICU they remain third‑line tools because of psychoactive side‑effects and oral‑only administration, but can salvage otherwise intractable nausea when used judiciously.