Ephedrine shows synergistic motor blockade when combined with bupivacaine or lidocaine for spinal anesthesia in a rat model

BACKGROUND: Ephedrine is a direct/indirect vasoactive drug. In addition, it also possesses intrinsic local anesthetic properties, mainly due to its sodium-channel blockage. We investigated whether ephedrine demonstrates a synergistic effect with bupivacaine and lidocaine when injected via a spinal catheter into the spinal space of rats. METHODS: Spinal catheters were surgically placed in 47 rats (n = 8 per group; 7 rats were excluded.) Bupivacaine, lidocaine, and ephedrine in various concentrations and constant volumes (60 μL) were injected into the spinal catheters to determine the equipotency of each drug. Ephedrine in combination with either bupivacaine or lidocaine was then injected into the spinal catheters. RESULTS: Ephedrine demonstrated statistically significant synergistic effects with bupivacaine as well as with lidocaine in fixed combinations. The combination index reflecting a synergistic effect was 0.792 (95% confidence interval: 0.665-0.919) for ephedrine + bupivacaine and 0.663 (95% confidence interval: 0.532-0.794) for ephedrine + lidocaine. CONCLUSION: Ephedrine combined with either bupivacaine or lidocaine acted synergistically to block motor function and has the potential to reduce the amount of local anesthetic needed for spinal block. The synergistic effect of ephedrine in combination with local anesthetics is an interesting pharmacological phenomenon that warrants further clinical evaluation.