Mixing Lidocaine with Benzathine Penicillin G: Dilution Recommendations
The mixture of 0.25 ml of lidocaine with BPG should NOT be further diluted with sterile water or any other solution—the lidocaine is directly mixed with the BPG powder or suspension as the diluent itself. 1, 2
Direct Mixing Protocol
Mix lidocaine directly with BPG without additional dilution. The lidocaine serves as the reconstitution diluent, replacing sterile water entirely 1, 2, 3
Use 1% lidocaine hydrochloride at doses of 0.2-0.4 mg/kg (typically 0.25-0.5 ml depending on patient size) mixed directly into the BPG vial 1, 2, 4
The total volume of lidocaine used should be sufficient to reconstitute the BPG powder to the appropriate concentration for injection—no additional sterile water is needed 2, 5
Evidence for Direct Mixing
Multiple randomized controlled trials demonstrate that lidocaine mixed directly with BPG (without additional dilution) significantly reduces immediate post-injection pain compared to BPG diluted with sterile water alone 1, 2, 3
A 2024 meta-analysis found that BPG diluted with lidocaine reduced immediate pain by a mean difference of -3.84 points on a 0-10 scale (moderate quality evidence) 3
Serum penicillin concentrations remain equivalent whether BPG is reconstituted with lidocaine or sterile water, confirming that direct lidocaine mixing does not compromise antibiotic efficacy 2
Alternative Local Anesthetics
Mepivacaine 1% (0.5 ml) can be used as an alternative to lidocaine, showing similar pain reduction when mixed directly with BPG 3, 5
Procaine mixed with BPG also demonstrates pain reduction, though the evidence quality is lower 3
Common Pitfall to Avoid
Do not add sterile water after mixing lidocaine with BPG. The lidocaine IS the diluent—adding sterile water would unnecessarily increase injection volume and potentially dilute the local anesthetic effect 1, 2
The only context where sterile water dilution is appropriate is when preparing oral sugar solutions for neonatal analgesia (an entirely different clinical scenario), not for parenteral medications like BPG 6
Clinical Impact
Pain reduction is most significant immediately after injection and at 5 minutes post-injection, with scores returning to baseline by 60 minutes 1, 4
No adverse events have been reported with lidocaine-BPG mixtures in multiple trials 1, 2, 3, 5
This approach improves adherence to long-term BPG prophylaxis regimens for rheumatic fever prevention 4