What prophylactic antiemetic therapy is recommended for patients with a high Apfel (Apfel Simplified Risk Score) score indicating increased risk of postoperative nausea and vomiting (PONV)?

Prophylactic Antiemetic Therapy for High Apfel Score Patients

Patients with an Apfel score ≥2 should receive combination prophylaxis with 2-3 antiemetics from different drug classes, selecting from 5-HT₃ receptor antagonists (ondansetron 4-8 mg IV, granisetron 0.35-3 mg IV), corticosteroids (dexamethasone 4-8 mg IV), NK₁ receptor antagonists (aprepitant, fosaprepitant), or dopamine antagonists (droperidol 0.625-1.25 mg IV). 1, 2

Risk Stratification Using Apfel Score

The Apfel simplified risk score assigns one point for each of four independent risk factors: 2

• Female gender
• Non-smoking status
• History of PONV or motion sickness
• Postoperative opioid use

Risk categories: 2, 3

• Low risk (0-1 factors): No routine prophylaxis needed
• Moderate risk (2 factors): 2 antiemetics from different classes
• High risk (3-4 factors): 2-3 antiemetics from different classes

First-Line Antiemetic Drug Selection

Most Effective Single Agents (High-Certainty Evidence)

NK₁ receptor antagonists (most effective drug class): 4

• Aprepitant: RR 0.26 for vomiting (ranked 3rd most effective single drug) 4
• Fosaprepitant 150 mg IV: RR 0.06 for vomiting (ranked 1st, moderate certainty) 4

5-HT₃ receptor antagonists: 1, 4

• Ramosetron: RR 0.44 for vomiting (ranked 5th) 4
• Granisetron: RR 0.45 for vomiting (ranked 6th), probably has no effect on adverse events 4
• Ondansetron 4-8 mg IV: RR 0.55 for vomiting (ranked 13th), FDA-approved for PONV prophylaxis in patients ≥1 month old 5, 4

Corticosteroids: 1, 4

• Dexamethasone 4-8 mg IV: RR 0.51 for vomiting (ranked 8th), reduces PONV up to 72 hours without increased adverse events in major GI surgery 1, 4

Dopamine antagonists: 1, 4

• Droperidol 0.625-1.25 mg IV: RR 0.61 for vomiting (ranked 20th, moderate certainty), may reduce serious adverse events and probably reduces headache 4

Dose-Response Considerations

Critical dosing thresholds for efficacy: 4

• Granisetron, dexamethasone, ondansetron, droperidol: Recommended and high doses show clinically important benefit; low doses do NOT show clinically important benefit
• Dexamethasone: 4-5 mg has similar efficacy to 8-10 mg for most outcomes 1
• Ondansetron: Recommended/high doses reduce sedation compared to placebo; 8 mg provides no additional benefit over 4 mg 5, 4

Combination Therapy Strategy

Drug combinations are generally more effective than single agents for preventing vomiting. 4 Each drug should reduce PONV risk by approximately 25% when given individually. 1

Recommended combinations for high-risk patients (Apfel ≥3): 1, 2

• 5-HT₃ antagonist + dexamethasone + NK₁ antagonist
• 5-HT₃ antagonist + dexamethasone + droperidol
• Any combination of 2-3 drugs from different classes

Adjunctive Risk Reduction Strategies

Non-pharmacologic interventions that reduce baseline PONV risk: 1, 2

• Total intravenous anesthesia (TIVA) with propofol instead of volatile anesthetics 1, 2
• Avoid nitrous oxide 1, 2
• Opioid-sparing multimodal analgesia (NSAIDs, acetaminophen, regional blocks) 1, 2
• Adequate hydration with mildly positive fluid balance 2
• Preoperative carbohydrate loading (400 mL with 50 g CHO, 2 hours before surgery) 1, 2

Rescue Therapy for Breakthrough PONV

If prophylaxis fails, administer a different drug class than what was used prophylactically—using the same class significantly reduces effectiveness. 1, 2 For patients who did not receive olanzapine prophylactically, it should be offered for breakthrough PONV. 1

Rescue options include: 1

• Different 5-HT₃ antagonist if not used prophylactically
• Dopamine antagonists (metoclopramide, though limited by side effects) 1, 6
• Antihistamines (promethazine—caution: sedation) 1
• Anticholinergics (scopolamine—caution: dry mouth, blurred vision) 1

Common Pitfalls to Avoid

Do not use routine prophylaxis in low-risk patients (Apfel 0-1) as the cost-benefit ratio does not support this approach, though some institutions are moving toward universal prophylaxis given low side-effect profiles. 1

Do not underdose antiemetics: Low doses of granisetron, dexamethasone, ondansetron, and droperidol lack clinically important benefit. 4

Do not repeat the same drug class for rescue therapy: This approach has significantly reduced effectiveness. 1, 2

Monitor for class-specific side effects: 4

• Ondansetron probably increases headache (RR 1.16) but reduces sedation
• Droperidol probably reduces headache (RR 0.76)
• Dexamethasone has no effect on sedation
• Long-term oncological effects of dexamethasone remain unknown 1

Safety Profile Summary

For the most effective antiemetics, safety evidence is limited: 4

• Serious adverse events: Very low to low certainty evidence for most drugs
• Granisetron probably has no effect on any adverse events (moderate certainty)
• Droperidol may reduce serious adverse events and any adverse events (low certainty)
• Dexamethasone and ondansetron may have little or no effect on any adverse events (low certainty)