Practice Perfect 732
Local Anesthetics Part 3: Should We Mix Anesthetics?

The last couple of Practice Perfect issues have focused on local anesthetics, specifically their history (Keeping it Local Part I: A History of Local Anesthetics) and clinical details (Keeping it Local Part 2: Anesthetic Details). I was going to move on to a new topic this week but couldn’t help throwing in one final topic to make this “Keeping It Local,” a trilogy if you will. Think of this common clinical scenario: You’re seeing a 16-year-old with an ingrown toenail, and you’re preparing to do a partial nail avulsion and matrixectomy. What local anesthetic are you going to use? Optimally, this would be one that has a rapid onset and is relatively long acting. Deciding to inject a combination of 1% lidocaine plain and 0.5% Marcaine® plain, you stop for a second and wonder, “Does it really matter if I inject a mix?” Let’s see if we can answer this clinical question.

Unfortunately, it will be difficult to provide a solid answer on this because the recent research is spartan, though its origins reach all the way back to the late 1950s. Let’s go high yield and show what the research has to say in a chart. For those who want to avoid the chart, skip down to the end.

Study Methodology Results Deficiencies For or Against Mixing
Defalque 19961 Epidurals in 12 dogs with combinations of lidocaine, tetracaine, and procaine.
  • Latencies between anesthetics and their combinations showed no differences.
  • Doubling concentrations of anesthetics had no effect on latency or duration of action.
  • Latency determined by fastest acting component.
  • Duration determined by most active component.
Epidurals in dogs not generalizable to locals in humans. For
Bromage 19722 183 patients, brachial plexus block w/ different combos of bupivacaine and lidocaine, alone, mixed, and with/without epi.
  • Latency time almost 4x faster with addition of lidocaine.
  • No difference in duration.
Lidocaine used was carbonated, not the HCl version used today.
No randomization
Cunningham 19743 Performed axillary blocks on 25 healthy patients w/either bupivacaine or combo w/ chloroprocaine.

Double blind RCT design.
  • Initial onset time shorter with lidocaine addition.
  • Time to max anesthesia significantly decreased with chloroprocaine addition.
  • Duration not affected by mixture versus alone.
Axillary block. For
Galindo 19804 36 rat sciatic nerve injections, bathed nerve in chloroprocaine, bupivacaine, or combo, looked at amplitude of action potential. Mixed injection behaved like chloroprocaine alone.

Long duration characteristic of bupivacaine not seen when mix injected.

Longer duration when pH of anesthetic increased.

Mix of injections didn’t behave according to individual properties.
Not generalizable to clinical practice. Against
Ribotsky 19965 Double blind, placebo controlled RCT of 12 subjects injected at 1st intermetatarsal space.

Used normal saline, lidocaine, bupivacaine, or mix.

Used other foot at saline injected control.

5.07 monofilament used to check sensation at 15, 25, 40, 60 and every 60 minutes until sensation returned.
Mix was 20 sec faster than bupivacaine alone (essentially no difference).

Significantly increased duration with bupivacaine alone versus mixed.
Not a standard block such as digital; researchers stopped testing subjects at 10 min and then made subjects responsible for testing themselves for sensation; after 60 minutes of anesthesia they then tested at 60 min intervals, which skews toward inaccurately greater measured duration Against
Cuvillon 20096 Double blind RCT design of sciatic & femoral blocks in 82 patients using bupivacaine, ropivacaine, or mixed, all with epi. Faster onset, shorter duration with mixture of anesthetics for sciatic-femoral blocks. Some issues with group allocation and reporting. For
Gadsden 20117 64 patients undergoing ultrasound-guided scalene block with bupivacaine, mepivacaine, or mix. Assessed time to block onset and duration No benefit to combination for duration if using bupivacaine Anesthetics used have very similar properties and pharmacology.

Didn’t use lidocaine.

Of the seven available studies, four are in support of mixing anesthetics and three argue against it. The major problem with this body of available research is the lack of generalizability to clinical practice for a variety of reasons (animal studies, nerve blocks in other parts of the body, and methodological flaws).

Desert Foot Online 2020

The two studies most applicable to podiatric practice, Ribotsky 1996 and Cuvillon 2009, make it a tie. Beware, though. Both have methodological issues that limit their applicability. So, as it stands now, the jury is out, and you can decide to mix your anesthetics or go solo. A properly powered randomized controlled trial using the hallux block comparing bupivacaine and bupivacaine + lidocaine (both without epinephrine) with careful monitoring of latency to onset of anesthesia and duration of action would help to put this issue to bed.

Best wishes.

Jarrod Shapiro, DPM
PRESENT Practice Perfect Editor
  1. Defalque RJ, Stoelting VK. Latency and duration of action of some local anesthetic mixtures. Anesth Analg. Jan-Feb 1966;45(1):106-116.
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  2. Bromage PR, Gertel M. Improved brachial plexus blockade with bupivacaine hydrochloride and carbonated lidocaine. Anesthesiology. 1972 May;36(5):479-487.
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  3. Cunningham NL, Kaplan JA. A rapid-onset, long-acting regional anesthetic technique. Anesthesiology. 1974 Nov;41(5):509-511.
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  4. Galindo A, Witcher T. Mixtures of local anesthetics: bupivacaine-chloroprocaine. Anesth Analg. 1980 Sep;59(9):683-685.
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  5. Ribotsky BM, Berkowitz KD, Montague JR. Local anesthetics. Is there an advantage to mixing solutions? J Am Podiatr Med Assoc. 1996 Oct;86(10):487-491.
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  6. Cuvillon P, Nouvellon E, Ripart J, Boyer JC, Dehour L, Mahamat A, L’hermite J, Boisson C, Vialles N, Lefrant JY, de La Coussaye JE. A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study. Anesth Analg. 2009 Feb;108(2):641-664.
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  7. Gadsden J, Hadzic A, Gandhi K, Shariat A, Xu D, Maliakal T, Patel V. The effect of mixing 1.5% mepivacaine and 0.5% bupivacaine on duration of analgesia and latency of block onset in ultrasound-guided interscalene block. Anesth Analg. 2011 Feb;112(2):471-447.
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