Chapter 99: Anti-Emetics and Aspiration Prophylaxis

INTRODUCTION

Several agents administered in the perioperative period (particularly anesthetics and analgesics) contribute to the potential for patients to develop postoperative nausea and vomiting (PONV). One measure to objectively assess and treat PONV is the Apfel score—1 point each for female gender, non-smoking status, history of PONV, and use of postoperative opioids. The score will dictate which combination of antiemetics could benefit the patient of that risk score. PONV may sound innocuous, but it can lead to pulmonary complications such as perioperative pulmonary aspiration, aspiration pneumonia, and related pulmonary compromise. Because of this, institutions have integrated antiemetics into their enhanced recovery after surgery (ERAS) protocols.

ANTIEMETICS

Dopaminergic Antagonists

• Phenothiazines: These widely used heterocyclic compounds, which contain nitrogen and sulfur, achieve antiemetic effects by antagonizing dopamine-2 (D₂) receptors clustered within the brain stem’s chemoreceptor trigger zone. The most used phenothiazines are promethazine (12.5–25 mg) and prochlorperazine (5–10 mg). Side effects include sedation secondary to histaminergic blockade and extrapyramidal reactions secondary to dopaminergic blockade. Children less than 2 years of age should not receive promethazine due to the risk of respiratory depression. Due to hepatic metabolism and biliary excretion, these drugs may also rarely cause liver injury (presenting in a cholestatic pattern). Extravasation of promethazine may potentially cause significant tissue injury such as gangrene. Although phenothiazines principally block central dopamine receptors, they also have mild antimuscarinic and antiadrenergic peripheral effects.

• Butyrophenones: Butyrophenones contain ketones with a phenyl ring and butyl chain. Droperidol is the principal antiemetic within this group. Droperidol primarily acts as a D₂ receptor antagonist but also has mild antihistamine, anti-serotonin, and anti-adrenergic activity. With its short half-life of 3 hours, droperidol is often part of ERAS protocols for patients with at least two risk factors for PONV. It can also be used as rescue therapy in the postoperative care unit. Since 2001, droperidol carries an FDA “black box” warning due to its potential for QT interval prolongation and risk of torsades de pointes. However, this risk is much lower when given in its lowest effective dose (0.625 mg).

• Benzamides: The principal benzamide antiemetic is metoclopramide. Its antiemetic effect is primarily achieved through central dopamine D₂-receptor blockade (along with lesser serotonin 5-HT₃ antagonism). In addition, metoclopramide also has peripheral pro-kinetic effects which add to its antiemetic properties. In the bowel, metoclopramide increases motility and peristalsis by stimulating peripheral D₂, 5-HT₄, and muscarinic acetylcholine receptors. It also increases lower esophageal sphincter tone. Metoclopramide may facilitate gastric emptying for patients that have gastroparesis, inadequate fasting status, and acid reflux disease—all conditions which incur risk for perioperative aspiration. Metoclopramide is contraindicated for patients with Parkinson’s disease, bowel obstruction, or pheochromocytomas. It crosses the blood-brain barrier and may cause extrapyramidal side effects secondary to dopaminergic blockade. It may also inhibit plasma cholinesterase. The muscarinic effects of metoclopramide on the bowel may ...