Debating Mixing Local Anesthetics: Best of Both Worlds or Playing With Fire?

Originally published by our sister publication Anesthesiology News

ORLANDO, Fla.—Should anesthesiologists mix local anesthetics for peripheral nerve blocks (PNBs)? The complicated, often contentious issue was debated during a session at the American Society of Regional Anesthesia and Pain Medicine 2025 annual spring meeting.

During the discussion, experts weighed in on which approach maximizes anesthetic benefits while ensuring patient safety.

Best of Both Worlds

In essence, the argument for mixing local anesthetics centers around the ability to utilize the characteristics of individual medications in order to layer them in ways that build on the strengths of each drug.

“Essentially, we want to try to harness the pharmacokinetic and pharmacodynamic advantages of each of the local anesthetics which are being combined together,” said Ellen M. Soffin, MD, PhD, an associate professor of anesthesiology and the vice chief of clinical affairs at the Hospital for Special Surgery, in New York City.

“It’s like the tortoise and the hare,” she said. “The hare takes off pretty quickly—this is what gets your block set—then the tortoise takes over and steadily runs the race. Ideally, you want both to cross the finish line together, resulting in better outcomes for patients.”

Yet, in recent years, mixing local anesthetics for PNBs has largely fallen from favor.

“It was perceived wisdom for how we did our upper extremity blocks when I was a fellow,” Soffin said. “However, there is a lot of data that suggests we shouldn’t be doing this.”

That said, she highlighted that there are certain conditions where mixing local anesthetics is advantageous and should be encouraged. “It’s an exciting time to be thinking about this, as the evidence is evolving and developing.”

A recent systematic review and meta-analysis of 19 randomly controlled trials, which included a total of 1,060 participants, found that mixed local anesthetics resulted in an 8.4-minute reduction in surgical block latency (Braz J Anesthesiol 2025;75[3]:844617). A much more meaningful reduction in latency—nearly 15 minutes—also was demonstrated for lower extremity blocks.

“The study found faster latency for mixed blocks or lower extremity blocks, and that overall—irrespective of block location or technique—your block will set up faster if you mix your locals,” Soffin said.

Mixing local anesthetics can also be useful for situations when performing blocks with a nerve stimulator, when ultrasound is either unavailable or unfavorable, or when working with trainees and novice practitioners.

In certain cases, mixing may allow for the creation of a tailored block duration.

“We have plenty of literature that shows that when we mix our locals we sacrifice the duration of our blocks,” Soffin said. “This is usually presented as a negative, but in the right patient or procedure, tailoring an intermediate duration block may be beneficial.”

No matter the approach, she noted the importance of ensuring that complex calculations involving dosage and toxicity be conducted carefully, ideally with the use of a guide such as the SafeLocal app, which was developed by a team at Johns Hopkins University.

Playing With Fire

In his counterargument, Michael R. Fettiplace, MD, PhD, an assistant professor at the University of Illinois Chicago, stressed that data—in this case, the majority of which does not support mixing local anesthetics—should guide clinical decisions.

“If we are going to do something, we should be using evidence in order to drive it,” he said.

And where the data do show potential benefits for mixing, the advantages are very small and come with accompanying risks.

A recent study found minimal shortening of sensory and motor block onset when local anesthetic mixtures were used, yet found that the duration of the blocks could be shortened (Reg Anesth Pain Med 2025 Jan 8. doi:10.1136/rapm-2024-106104).

Such small differences are unlikely to play a meaningful role in the workloads of all but a selected few medical centers.

“If you are in a high-production center where you are running back and forth between your pre-op and OR and you really need a few extra minutes of time, then there may be some benefit,” Fettiplace said.

Yet, the potential benefit comes with a considerable downside via a substantial reduction in overall block time of approximately 25%.

While the idea of layering local anesthetics to establish an initial fast block, then have persistent pain controlled once the initial anesthetic is eliminated may make sense, he said, the reality is far more complex.

“You have multiple drug states—a resting state, an open state and an inactive state—where the drugs will bind at very different rates,” Fettiplace said. As drug concentrations drop and a drug such as lidocaine unbinds from sodium channels, instances of breakthrough pain can occur.

He also mentioned that since toxicity is likely additive, mixing local anesthetics can greatly increase the risk for adverse interactions.

“There are years and years of data—both older and more recent—which demonstrate that you anticipate additive interactions between these drugs,” Fettiplace said. “If people are giving full doses of each of the anesthetics with no accounting for mixing, it will result in a problem.”

—By Ethan Covey

Fettiplace and Soffin reported no relevant financial disclosures.