Toxic effects of local anesthetics on rat fibroblasts: An in-vitro study

J Orthop Sci. 2024 Apr 25:S0949-2658(24)00060-5. doi: 10.1016/j.jos.2024.04.003. Online ahead of print.


Background: Infusion catheters facilitate a controlled infusion of local anesthetic (LA) for pain control after surgery. However, their potential effects on healing fibroblasts are unspecified.

Methods: Rat synovial fibroblasts were cultured in 12-well plates. Dilutions were prepared in a solution containing reduced-serum media and 0.9% sodium chloride in 1:1 concentration. Each well was treated with 500 μl of the appropriate LA dilution or normal saline for 15- or 30-min. LA dilutions included: 0.5% ropivacaine HCl, 0.2% ropivacaine HCl, 1% lidocaine HCl and epinephrine 1:100,000, 1% lidocaine HCl, 0.5% bupivacaine HCl and epinephrine 1:200,000, and 0.5% bupivacaine HCl. This was replicated three times. Dilution of each LA whereby 50% of the cells were unviable (Lethal dose 50 [LD50]) was analyzed.

Results: LD50 was reached for lidocaine and bupivacaine, but not ropivacaine. Lidocaine 1% with epinephrine is toxic at 30-min at 1/4 and 1/2 sample dilutions. Bupivacaine 0.5% was found to be toxic at 30-min at 1/2 sample dilution. Bupivacaine 0.5% with epinephrine was found to be toxic at 15- and 30-min at 1/4 sample dilution. Lidocaine 1% was found to be toxic at 15- and 30-min at 1/2 sample dilution. Ropivacaine 0.2% and 0.5% remained below LD50 at all time-points and concentrations, with 0.2% demonstrating the least cell death.

Conclusions: Though pain pumps are generally efficacious, LAs may inhibit fibroblasts, including perineural fibroblast and endoneurial fibroblast-like cells, which may contribute to persistent nerve deficits, delayed neurogenic pain, and negatively impact healing. Should a continuous infusion be used, our data supports ropivacaine 0.2%.

Level of evidence: Basic Science Study; Animal model.

Keywords: Anesthesia; Bupivacaine; Lidocaine; Ropivacaine; Rotator cuff; Shoulder.