In this study, researchers determined the effect of bupivacaine alone and in combination with the adjuncts epinephrine or clonidine on nerve blood flow and tissue oximetry in a large animal model, simulating human conditions. Local anesthetics and epinephrine, used as an adjunct, are known to have a negative impact on nerve blood flow.

Nerve blood flow has a critical role in acute and chronic pathologies in peripheral nerves. Influences of local anesthetics and adjuvants on tissue perfusion and oxygenation are deemed as relevant factors for nerve damage after peripheral regional anesthesia. The link between low tissue perfusion due to local anesthetics and resulting tissue oxygenation is unclear.

The blood supply to peripheral nerves is delivered by two integrated, but functionally independent, vascular systems. Extrinsic and intrinsic vessels form anastomoses at the level of the epineurium. Alterations in blood flow are important for peripheral nerve pathology in acute and chronic disease. Our results showed that the application of local anesthetics alone, such as bupivacaine, resulted in relevant nerve blood flow reductions at T30 and T60, as shown in previous studies.

However, no significant difference for tissue oximetry between bupivacaine versus saline or versus bupivacaine in combination with clonidine or epinephrine was observed. Moreover, the addition of epinephrine or clonidine did not result in any significant alterations of nerve blood flow or tissue oximetry (SO2), compared with the bupivacaine standard group.

Epinephrine enhances nerve block duration, mostly due to reduction of local tissue clearance and prolonged concentration of the local anesthetic in the nerve and perineural tissue. It is regularly used as an adjunct for local anesthetics to reduce systemic absorption and consecutive toxic phenomena of the injected local anesthetic.

Furthermore, many clinicians assume a shortened nerve block onset time and prolonged anesthetic nerve blockade when epinephrine is used. Neurotoxicity of local anesthetics is not caused solely by ischemia as a result of reduced tissue perfusion. Bupivacaine was shown to be a weak uncoupler of mitochondrial oxidative phosphorylation resulting in apoptosis in neural cells.

In conclusion, study examined that a bupivacaine does show a relevant depression of nerve blood flow without resulting in severe nerve tissue ischemia. Thus, impairment of nerve blood flow by bupivacaine alone is not modified in a relevant way by the combination of bupivacaine with clonidine.

Ischemia as a consequence of the use of bupivacaine alone or in combination with epinephrine or clonidine was a rare event in our experimental study. Thus, ischemia is not a potential clinical relevant risk factor of peripheral nerve damage resulting from the administration of the aforementioned drugs.