PONV Prophylaxis: Serotonin Antagonists

Serotonin (5-hydroxytryptamine) receptor antagonists, particularly the 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, play a crucial role in preventing and managing postoperative nausea and vomiting (PONV). Their distinct advantage lies in their lack of sedative effects during the postoperative period. Consequently, some practitioners opt to reserve these drugs for potential use in the post-anesthesia care unit (PACU), avoiding their intraoperative administration.

First-generation serotonin antagonists: This category includes ondansetron, granisetron, dolasetron, and tropisetron. At equipotent doses, these medications demonstrate comparable efficacy in reducing PONV. Ondansetron, in particular, is widely utilized due to its cost-effectiveness and favorable side effect profile. However, it's crucial to note that all these drugs carry the potential to prolong electrocardiogram intervals, notably the QT interval. Thus, caution is warranted in patients predisposed to QTc prolongation or already taking medications that may exacerbate this risk. The US Food and Drug Administration (FDA) mandated a label update for ondansetron in 2021. These agents are typically administered as a single intravenous (IV) dose at the conclusion of surgery. Ondansetron is also available in orally disintegrating formulations, which can be administered at double the IV dose, proving equally effective when given 30 to 60 minutes preoperatively. The orally disintegrating tablet (ODT) form of ondansetron is particularly convenient for post-discharge use and may be suitable for children aged five and above.

Dosages:

• Ondansetron: Adults - 4 mg IV or 8 mg orally preoperatively; Children - 0.1 mg/kg IV, maximum 4 mg.
• Granisetron: Adults - 0.35 to 3 mg IV; Children - 40 mcg/kg IV, maximum 0.6 mg.
• Dolasetron: Adults - 12.5 mg IV; Children - 0.35 mg/kg IV, maximum 12.5 mg. Notably, dolasetron is contraindicated at higher doses previously used for preventing chemotherapy-induced nausea and vomiting (CINV) due to QTc prolongation risk.
• Tropisetron: Adults - 2 mg IV at surgery's end.

Second-generation serotonin antagonist:

• Palonosetron: Distinguished as a second-generation serotonin antagonist, palonosetron offers higher receptor binding affinity and an extended half-life of 40 hours compared to first-generation counterparts. It demonstrates similar efficacy in PONV prevention and is particularly beneficial for late or post-discharge nausea and vomiting (PDNV) owing to its prolonged action. Importantly, palonosetron does not appear to affect the QT interval. Its 0.075 mg IV dose at anesthesia induction is more efficacious in preventing PONV compared to several other antiemetics.

Dosage:

• Palonosetron: Adults - 0.075 mg IV at anesthesia induction; Children - 0.5 to 1.5 mcg/kg IV.