Perioperative Antiemetics

Perioperative antiemetics prevent and treat postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting. PONV occurs in about 30% of surgical patients and 80% of those at highest risk, delays discharge, and can cause dehydration, wound dehiscence, aspiration and electrolyte disturbance. Prophylaxis is directed by individual risk, and rescue uses a different class from the prophylactic drug.

Risk assessment. The Apfel score counts four factors: female sex, non-smoking status, previous PONV or motion sickness, and expected postoperative opioids. With 0, 1, 2, 3 or 4 factors the risk is about 10%, 20%, 40%, 60% and 80%. Procedure type (laparoscopic, gynaecological, strabismus, middle ear), volatile anaesthesia, nitrous oxide and longer surgery add risk.

Mechanism and classes.

• 5-HT3 antagonists (ondansetron, granisetron, palonosetron): block serotonin receptors in the gut and brainstem.
• Corticosteroid (dexamethasone): antiemetic mechanism uncertain, with added analgesic effect.
• Dopamine D2 antagonists (droperidol, haloperidol, amisulpride, metoclopramide).
• Antihistamines and anticholinergics (cyclizine, promethazine, hyoscine).
• NK1 antagonists (aprepitant, fosaprepitant).
• Propofol-based anaesthesia, which has an antiemetic effect.

Pharmacokinetics. Ondansetron half-life 3 to 4 hours; granisetron 9 hours; palonosetron 40 hours; dexamethasone effect lasts 24 hours or longer; hyoscine patch 72 hours; aprepitant 9 to 13 hours.

Children. Ondansetron 0.1 mg/kg (maximum 4 mg); dexamethasone 0.15 mg/kg (maximum 5 mg); droperidol 10 to 15 micrograms/kg.

Rescue. Use a drug from a different class from the one already given, and do not repeat a 5-HT3 antagonist within 6 hours or repeat dexamethasone; cyclizine 50 mg, haloperidol 0.5 to 1 mg or amisulpride 10 mg are typical choices.

• First-line. Dexamethasone at induction plus ondansetron at the end of surgery for patients at moderate risk.
• Alternative. Cyclizine, droperidol, haloperidol or amisulpride as the second or third agent; hyoscine patch where oral and injectable drugs are limited.
• Specialist. Aprepitant or fosaprepitant for high risk, and total intravenous anaesthesia with propofol; palonosetron for prolonged protection.
• Emergency. Treatment of established vomiting after surgery with a different class; hospital review for bowel obstruction or ileus.

Risk-based strategy.

• Apfel 0 to 1 and low-risk surgery: none or one drug.
• Apfel 2: two drugs from different classes.
• Apfel 3 to 4 or high-risk surgery: two to three drugs plus propofol anaesthesia, avoidance of volatile agents and nitrous oxide, adequate hydration and opioid-sparing analgesia.

Reduce baseline risk. Use regional anaesthesia where possible, minimise opioids, give intravenous fluids, avoid nitrous oxide.

Contraindications.

• 5-HT3 antagonists: hypersensitivity; congenital long QT syndrome; apomorphine use.
• Droperidol, haloperidol, amisulpride: prolonged QT, hypokalaemia, hypomagnesaemia, Parkinson disease (for droperidol and haloperidol), phaeochromocytoma.
• Cyclizine: severe heart failure, raised intracranial pressure, mechanical obstruction.
• Hyoscine: narrow-angle glaucoma, urinary retention, paralytic ileus.
• Metoclopramide: gastrointestinal obstruction, perforation or haemorrhage; phaeochromocytoma.
• Aprepitant: concurrent pimozide.

Serious adverse effects. QT prolongation and torsades de pointes (droperidol with boxed-warning-level concern, haloperidol, ondansetron, amisulpride at higher doses); extrapyramidal reactions and dystonia (dopamine antagonists); hyperglycaemia (dexamethasone); sedation and anticholinergic effects (cyclizine, promethazine, hyoscine); constipation and headache (5-HT3 antagonists); serotonin syndrome is rare.

Major interactions. QT-prolonging drugs (macrolides, fluoroquinolones, antipsychotics, methadone, class III antiarrhythmics) add risk; aprepitant raises dexamethasone exposure and lowers warfarin and hormonal contraceptive effect; CYP3A4 inducers lower aprepitant; apomorphine with ondansetron causes profound hypotension; levodopa antagonised by dopamine blockers.

Common prescribing errors.

• Giving the same class twice for rescue.
• Ignoring the QT interval and electrolytes.
• Cyclizine in heart failure.
• Dexamethasone in uncontrolled diabetes without glucose monitoring.
• Droperidol or haloperidol in Parkinson disease.
• Treating established vomiting with no assessment for obstruction.

Special groups.

• Pregnancy: ondansetron has a small possible first-trimester association with oral clefts, so use after the first trimester or when benefit outweighs risk; cyclizine and metoclopramide acceptable; hyoscine and promethazine sedating.
• Breastfeeding: ondansetron, cyclizine and metoclopramide are compatible with usual doses.
• Children: weight-based dosing; avoid promethazine under 2 years (respiratory depression) and metoclopramide in young children (dystonia).
• Older adults: avoid hyoscine patch and promethazine where possible because of confusion.
• Kidney: no adjustment for ondansetron; cyclizine caution.
• Liver: ondansetron maximum 8 mg daily in severe impairment; droperidol caution.
• East Africa: ondansetron and dexamethasone are widely available; droperidol, amisulpride and aprepitant often are not, so plan combinations from ondansetron, dexamethasone and cyclizine or haloperidol.

Monitoring. ECG and electrolytes in patients on QT-prolonging drugs; blood glucose after dexamethasone in diabetes; nausea and vomiting score for the first 24 hours; hydration and oral intake.

Referral and escalation. Persistent vomiting beyond 24 hours; bowel obstruction or ileus; torsades de pointes (magnesium sulphate 2 g intravenously and urgent cardiology input); dystonic reaction (procyclidine 5 mg intravenously or benzatropine); suspected raised intracranial pressure.

Comparison with alternative classes. Antiemetics from different classes act additively, so combining two or three gives greater reduction than increasing one dose. Nonpharmacological measures (propofol anaesthesia, hydration, avoiding nitrous oxide and opioids) are as effective as a single drug.