♦️ Introduction
In the OR, moments before induction, a patient winces as propofol enters a small dorsal hand vein. This scene is common: approximately 60% of patients experience injection pain, with many rating it as severe. The good news: simple, evidence-based steps—optimal vein choice and appropriate lidocaine use—can cut the incidence to 14–30% and facilitate smoother induction.
♦️ Why Does Propofol Cause Injection Pain?
Propofol is a lipid emulsion whose phenolic structure directly irritates vascular endothelium while promoting bradykinin release. Small dorsal hand veins, with their slower flow, allow higher local drug concentrations that intensify nociceptor activation. In contrast, larger vessels with rapid flow quickly dilute the emulsion, minimizing endothelial contact and reducing pain signals.
♦️ What Is the Most Effective Single Intervention?
Choose the antecubital vein rather than hand veins whenever possible. Compared with dorsal hand placement, antecubital access reduces pain to approximately 14% (RR 0.14; ≈1 in 7 vs ≈3 in 5 patients). This dramatic improvement likely stems from the vessel’s larger diameter and the immediate dilution effect. When peripheral hand access cannot be avoided, reassess vein options during pre-induction assessment and secure the largest available vessel.
♦️ How Should Lidocaine Be Used for Maximum Benefit?
Administer 20–40 mg of lidocaine intravenously.
Both pretreatment (giving lidocaine just before propofol) and admixture (mixing lidocaine with propofol) demonstrate comparable efficacy (odds ratios 0.13–0.19), cutting the rate of severe pain from approximately 38% (≈2 in 5 patients) down to roughly 12% (≈1 in 8). For enhanced effect, combine lidocaine pretreatment with 30–60 seconds of venous occlusion using a tourniquet before propofol injection—this approach further lowers pain incidence (relative risk 0.29).
⚠️ Critical Safety Note: Mixing lidocaine with propofol increases lipid particle size and destabilizes the emulsion, raising theoretical concerns about embolism. Therefore:
- Prepare immediately before use
- Prefer pretreatment for safety
- If admixing, inject without delay and never store
💡 Understanding the Difference
Think of the two approaches like seasoning a dish: pretreatment is adding salt to prepare the palate (anesthetizing the vessel wall) before introducing the main ingredient (propofol).
Admixture is mixing the seasoning into the ingredient itself. While both methods work equally well for pain reduction, the admixture approach carries the additional concern of changing the “ingredient’s quality” (emulsion stability), which is why pretreatment is considered the safer standard procedure.
♦️ What Are the Alternatives When Lidocaine Cannot Be Used?
Several options provide moderate benefit when lidocaine is contraindicated:
🔹 Opioid Pretreatment:
A small dose of fentanyl or similar opioid administered before propofol can cut pain incidence roughly in half (relative risk 0.49). However, respiratory depression risk requires careful monitoring.
🔹 Ketamine Pretreatment:
Administering 0.1 mg/kg of ketamine demonstrates moderate effectiveness (relative risk 0.52).
🔹 Acetaminophen:
Intravenous acetaminophen shows pain-reducing effects, though evidence regarding its comparative effectiveness with lidocaine is mixed.
A 2025 randomized trial found no statistical difference in mean pain scores between acetaminophen, lidocaine, and fentanyl, while earlier meta-analyses suggested lidocaine was superior. Clinical significance remains uncertain.
📝 Take Home Messages
Summary: Propofol injection pain affects 60% of patients but can be reduced to 14–30% through evidence-based vein selection and lidocaine use, improving patient comfort and induction quality.
- ⭐ First-Line Approach: Use antecubital or other large veins when feasible (RR 0.14; reduces pain by ~85%)
- 💊 Lidocaine Administration: Give 20–40 mg by pretreatment (preferred for safety) or admixture (both equally effective for pain reduction)
- 📋 Maximum Effect Technique: Combine lidocaine pretreatment with 30–60 seconds of venous occlusion before propofol injection (RR 0.29)
- 🔄 Alternative Strategies: When lidocaine is contraindicated, consider low-dose opioid pretreatment or ketamine 0.1 mg/kg
- ⚠️ Safety Priority: Never store lidocaine-propofol admixtures; prepare and inject immediately; pretreatment avoids emulsion destabilization concerns
- 💡 Clinical Context: With remifentanil infusion during induction, pain is often minimal and specific interventions may be unnecessary
📚 References & Further reading
- Jalota L, et al. Prevention of pain on injection of propofol: systematic review. BMJ. 2011;342:d1110. doi:10.1136/bmj.d1110. Available from: https://www.bmj.com/content/342/bmj.d1110 [Open Access]
- Euasobhon P, et al. Lidocaine for reducing propofol-induced pain on induction. Mahidol Univ. 2016; [Open Access]
- Folino TB, et al. Propofol. StatPearls. 2023; Available [Open Access]
Nazemroaya B, et al. Preventive Effects of Lidocaine, Fentanyl, Acetaminophen on Propofol Injection Pain. Front Pharmacol. 2025; [Open Access].
🔗 Related articles
⚠️ Disclaimer
This article is provided for medical education purposes and is not a substitute for medical advice or treatment. Clinical decisions should be based on the latest guidelines, individual patient circumstances, and the judgment of the treating physician.
Contact: If you have any concerns about this content, please contact contact@classicanesthesia.com.