Block-prolonging Effect of Epinephrine: Pharmacodynamic or Pharmacokinetic Mechanism? Bernards et al. (page 962)

Abstract

To determine whether epinephrine alters local clearance of lidocaine after peripheral nerve block in humans, Bernards et al. recruited eight volunteers. On the study day, the team inserted microdialysis probes in subjects’ left and right feet, adjacent to their superficial peroneal nerves. Then, either plain lidocaine (1%) or lidocaine with epinephrine (2.5 μg/ml) was injected along first one and then the other peroneal nerve in a double-blind, randomized fashion. The relative concentration of lidocaine in the tissue surrounding the microdialysis probe could then be assessed by measuring the drug in the dialysate fluid pumped through the catheter.Lidocaine concentration in the dialysate was measured at 5-min intervals, and cutaneous blood flow was assessed by laser Doppler at 10-min intervals for 5 h. The team then fit the lidocaine concentration-versus -time data to a two-compartment model using SAAM II modeling software.Pain, touch, and cold sensation were completely blocked in both groups after injection, but duration of the block was significantly longer for all three sensory modalities in the epinephrine group. All “plain lidocaine” blocks resolved before the end of the 5-h period, but touch, cold sensation, and pin prick were still blocked after 5 h in several subjects who had received epinephrine. The results suggested that epinephrine prolonged sensory block by decreasing local blood flow and slowing clearance. There was no evidence of any pharmacodynamic effects of epinephrine.