🤢 Designing an “Anti-Emetic Anesthetic”: How to Prevent Postoperative Nausea and Vomiting (PONV)

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Contents

♦️ Introduction

After anesthesia, when the surgery is over and everything seems fine, the patient suddenly murmurs,

“Ugh… I feel sick… I might throw up…”🤮

That distressing moment is PONV — postoperative nausea and vomiting.

Without prophylaxis, it occurs in about 30% of all surgical patients under general anesthesia,
and in up to 80% of high-risk patients.
It’s one of the leading causes of postoperative discomfort and dissatisfaction — along with shivering and pain.

The good news: with evidence-based prevention, PONV can be dramatically reduced.

♦️ Step1：Quantify the Risk — The Apfel Score

🔷 Apfel Score

Risk Factor	Description
👩 Female sex	About 2–3× higher risk than males
🚭 Non-smoker	Smoking appears to have a protective effect
🤢 History of PONV or motion sickness	Indicates individual susceptibility
💊 Postoperative opioid use	Potent trigger for nausea/vomiting

Total Apfel Score	Estimated PONV risk
0	≈10%
1	≈20%
2	≈40%
3	≈60%
4	≈80%

💡 Interpretation:

0–1 = low risk (single agent often sufficient)
2 = moderate risk (dual prophylaxis)
≥3 = high risk (multimodal approach: ≥3 agents)

The Apfel score remains the most widely used global standard and is reaffirmed in the Fourth Consensus Guidelines (Gan TJ et al., Anesth Analg 2020).

📖 Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N.
A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers.
Anesthesiology. 1999;91:693–700.

🔷 Pediatric Variant — The POVOC Score

Factor	Description
⏱ Surgery duration ≥ 30 min	Longer procedures raise risk
👦 Age ≥ 3 years	Older children more susceptible
👁 Strabismus surgery	High-risk category
👨‍👩‍👧 Family or patient history of PONV/motion sickness	Genetic tendency

📖 Eberhart LHJ et al. Anesth Analg. 2004;99:1630–1637.

♦️ Step 2: Lower the Baseline Risk — “Make the Anesthetic Less Emetic”

Before adding drugs, optimize the anesthetic technique itself:

🌿 Use total intravenous anesthesia (TIVA) with propofol → Reduces PONV 3–5-fold compared with volatile agents.
❌ Avoid nitrous oxide when possible.
💉 Minimize opioids (multimodal analgesia: acetaminophen, NSAIDs, regional blocks).
💧 Adequate IV hydration.
⚙️ Avoid large doses of neostigmine; consider sugammadex for reversal.

✅ These baseline adjustments often halve PONV incidence before pharmacologic prophylaxis.

💊 Step 3: Pharmacologic Prophylaxis — Evidence-Based Regimens

🌎 Global standard (per 2020 Consensus):

Combine drugs with different mechanisms for additive protection.
Base the number of agents on risk level (Apfel score).

Drug	Recommended Timing	Typical Dose	Notes
Dexamethasone	Induction	4–8 mg IV	Cornerstone agent; early administration more effective.
Ondansetron	End of surgery	4 mg IV	Most widely used 5-HT₃RA; 8 mg oral ODT also effective.
Granisetron	End of surgery	0.35–3 mg IV	Slightly longer half-life.
Palonosetron	End of surgery	0.075 mg IV	Long-acting; useful for PDNV prevention.
Droperidol	End of surgery	0.625 mg IV	Highly effective; monitor QTc.
Haloperidol	End of surgery	0.5–1 mg IV	Alternative when droperidol unavailable.
Aprepitant (NK₁RA)	Induction	40 mg PO	Long-acting; prevents vomiting > nausea.
Transdermal scopolamine	Evening before → 2 h preop	1 patch	FDA-approved; useful for outpatients.

💡 Preferred combinations

Moderate risk (2 factors): dexamethasone + 5-HT₃RA
High risk (≥3 factors): dexamethasone + 5-HT₃RA + NK₁RA or scopolamine or droperidol

🇯🇵 In Japan: ondansetron, granisetron, and palonosetron are now officially approved for PONV, whereas dexamethasone use remains off-label.

🚨 Step4：Rescue Treatment — If PONV Occurs

Even with optimal prophylaxis, breakthrough PONV can happen.
Key rule:

🔁 Choose a drug from a different pharmacologic class than what was used for prophylaxis.

If prophylaxis included a 5-HT₃RA → use droperidol, haloperidol, or promethazine.
If dexamethasone alone was given → use a 5-HT₃RA.
Re-dosing the same class within 6 hours is usually ineffective.

🇺🇸 In the U.S., amisulpride (Barhemsys) is now FDA-approved for both prophylaxis and rescue of PONV (5 mg IV for prevention, 10 mg IV for rescue), following failure of other classes.
(Not yet widely approved in Asia.)

🕒 Step 5：Don’t Forget PDNV — Post-Discharge Nausea and Vomiting

Especially relevant for ambulatory surgery. Five PDNV risk factors:

Female sex
Age < 50 years
Prior PONV or motion sickness
Nausea in PACU
Opioid use in PACU

PDNV score	Estimated incidence
0–1	10–20%
2–3	30–50%
4–5	60–80%

Use long-acting antiemetics (palonosetron, aprepitant, scopolamine TTS) when PDNV risk is high.
Outpatient follow-up instructions should include hydration and rescue antiemetic guidance.

📖 Apfel CC et al., Anesth Analg 2012.

📝 Summary: Take Home Points

✅ Quantify risk: Apfel (adults), POVOC (children), PDNV score (outpatients).
✅ TIVA + opioid-sparing + hydration = first-line risk reduction.
✅ Use multimodal prophylaxis — combine agents with different mechanisms.
✅ Dexamethasone (induction) + 5-HT₃RA (end of case) = evidence-based core.
✅ For high-risk patients, add NK₁RA, droperidol, or scopolamine.
✅ Rescue with a different class if symptoms occur within 6 hours.
✅ Plan for PDNV in outpatients with long-acting drugs.