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Ondansetron (Zofran)

Anesthesia Implications

Updated On: July 10, 2026

Classification:
Selective serotonin receptor (5-HT3) antagonist
Therapeutic Effects:
PONV prophylaxis, Reducing Spinal anesthesia induced hypotension
Time to Onset:

< 30 minutes

Time to Peak Effects:

Variable

Duration:

12-24 hours

Primary Considerations:

Slow Push - The most common side effect of this drug is a headache, which has been associated with a rapid bolus. Ideally, Zofran should be given over 2-5 minutes. In any case, Zofran should NOT be given over less than 30 seconds. Coadministration - Zofran by itself will reduce PONV by up to 33%. Coadministration of dexamethasone (Decadron) or methylprednisolone will have additive affects. OB - Zofran DOES cross the placenta AND also into breast milk. Use with caution in the parturient and breastfeeding mothers. Dysrhythmias - Zofran can cause dysrhythmias, specifically when combined with metoclopramide. Tramadol - Ondansetron reduces the analgesic affects of tramadol.

IV push dose:

Adult and pediatric PONV prophylaxis: 0.10 - 0.15 mg/kg Reducing Spinal anesthesia induced hypotension: 4-8 mg IV just prior to LA in the intrathecal space

Method of Action:

Serotonin (5-HT3) receptors can be found peripherally on vagal nerves as well as centrally in the chemoreceptor trigger zone (CTZ). Zofran is a serotonin antagonist at both of these sites, which helps to eliminate/reduce the emetic effects that serotonin would produce. Zofran is also useful to treat spinal anesthesia induced hypotension.  In this case, ondansetron is believed to inhibit the reflexive drop in heart rate as a result of spinal anesthesia (otherwise known as the Benzold-Jarisch reflex)

Metabolism:

Hepatic

Additional Notes:

Some studies show that Zofran is more effective at preventing vomiting versus nausea.


Reference

Omoigui. Sota Omoigui's anesthesia drugs handbook. Fourth edition. 2012.p. 376-379
Nagelhout. Nurse anesthesia. 6th edition. 2018.p. 1027
Zhang. Effect of ondansetron in preventing postoperative nausea and vomiting under different conditions of general anesthesia: A preliminary, randomized, controlled study. 2013
Cruz. Timing of ondansetron administration to prevent postoperative nausea and vomiting. 2008
Norred. Antiemetic prophylaxis: Pharmacology and therapeutics. AANA Journal. 2003
Zofran (ondansetron) FDA label. 2025.link
Griddine A, Bush JS. Ondansetron. StatPearls. Updated 2023.link
Ondansetron for spinal hypotension: meta-analysis. 2022.link