Clearing Up Common Misconceptions Regarding Local Anesthetics

For some reason, one of the topics in medicine that I find is ripe with misinformation is in the realm of local anesthetics, something that some podiatrists use on a daily basis. I have busted one of these myths before regarding the use of epinephrine.¹ However, this barely scratches the surface when it comes to misconceptions regarding anesthetics.

Should You Mix Your Local Anesthetics?

A semi-common practice in operating rooms that I’ve observed is mixing local anesthetics. An example is a short-acting, fast-onset anesthetic, like lidocaine, mixed with a long-acting, slow-onset anesthetic, like bupivacaine. Explanations that I have heard are that it gives the best of both worlds: a local anesthetic with a fast onset that is also very long-acting.
 
Well, like many things in medicine, the theory is sound, but what actually happens may surprise you. Turns out, mixing anesthetics has no benefit at all and actually decreases the duration compared to using bupivacaine alone while increasing the onset compared to using lidocaine alone.² So, not only does it not help, but mixing actually is not as efficacious as just using bupivacaine. This has been reproduced not only in the foot, but also several other anatomic areas.^3-5 The recommendation remains the same: do not mix your local anesthetics! If you want the longest onset, use bupivacaine with or without epinephrine. If you inject prior to surgical prep as well, there are several minutes of prepping, draping, timeouts, etc., before the procedure starts, leaving ample time for the bupivacaine to work.⁶

Is Bupivacaine Chondrotoxic?

A very widespread belief is that bupivacaine should not be used for intra-articular injections, as it has the potential to kill chondrocytes and damage cartilage. That idea is based on preclinical science and in vitro studies. While it is true that many local anesthetics have a dose/time dependent relationship with chondrocyte death and bupivacaine has been found to be chondrotoxic in several studies, this is likely only clinically relevant with continuous infusion catheters.^7-12 There is unlikely to be any harm with a single injection of bupivacaine (or any local anesthetic).¹³ Based on these data and findings, avoiding bupivacaine for therapeutic or diagnostic intra-articular injections because it is “chondrotoxic” is not supported by evidence.¹⁰ There is even some evidence to suggest that lidocaine may be more chondrotoxic than any local anesthetic alternative.¹⁴
 
Several in vitro studies have demonstrated that almost anything is chondrotoxic (lidocaine, bupivacaine, epinephrine, saline).^7,10,15 Because of this, it is also important to understand that the in vivo environment is considerably different than chondrocyte cells in a petri dish. Intact hyaline cartilage in human joints is protective, there is local absorption of the drug into various structures, dilution of drug by synovial fluid (and possible arthroscopic lavage fluid), and ongoing reparative processes.¹³ Protecting cartilage is of course important, but following available evidence, single injections into joints can be safely done with any local anesthetic of your choosing. However, long-term catheters and continuous intra-articular infusions should be avoided.

What About Liposomal Anesthetics?

There are several techniques to try to increase the rate of release of local anesthetics, making them incredibly long-acting compared to standard anesthetics used today. One of the more popular ones is a liposomal bupivacaine that claims to numb patients for up to 96 hours after their injection. However, a recent independent meta-analysis from 2021 demonstrated no clinically significant improvement with liposomal bupivacaine versus plain anesthetic in patients undergoing various orthopedic and general surgery procedures.¹⁶ A recent Cochrane Review also failed to demonstrate any benefit over plain anesthetic.¹⁷
 
Now, this may be one of the many cases in medicine where the theoretical mechanism of action is different from what actually happens in vivo (similar to the above myth of mixing local anesthetics). There are several plausible explanations for why liposomal bupivacaine is not demonstrating clear superiority. One of these is the pH disparity with liposomal bupivacaine, which remains extracellular and does not penetrate cells. This interrupts signal transmission and decreases efficacy. After injection of bupivacaine, there is a local inflammatory response, which decreases the local pH, thus impeding tissue penetration by the bupivacaine molecules from the lipid carriers. This may be one of the reasons why liposomal bupivacaine is not exhibiting higher clinical effectiveness than the plain anesthetic.¹⁶

In Conclusion

There is still much to learn regarding local anesthetics. However, based on available data, there is no need to mix your locals as it will decrease efficacy, bupivacaine is OK to inject intra-articularly as long as it is not an infusion catheter, and the literature on liposomal bupivacaine does not clearly support a contribution to better outcomes.
 
Dr. Ehlers is in private practice in Arvada, CO, and is an attending at the Highlands-Presbyterian/St. Luke’s Podiatric Residency Program. He finds interest in debunking medical myths and dogma.
 
References
1.    Ehlers T. Is it true that epinephrine can cause necrosis in areas of end-arterial circulation? Podiatry Today. Published Sept. 29, 2022.
2.    Ribotsky BM, Berkowitz KD, Montague JR. Local anesthetics. Is there an advantage to mixing solutions? J Am Podiatr Med Assoc. 1996 Oct;86(10):487-91. doi: 10.7547/87507315-86-10-487. PMID: 8918026.
3.    Vinycomb TI, Sahhar LJ. Comparison of local anesthetics for digital nerve blocks: a systematic review. J Hand Surg Am. 2014 Apr;39(4):744-751.e5. doi: 10.1016/j.jhsa.2014.01.017. Epub 2014 Mar 5. PMID: 24612831.
4.    Sepehripour S, Dheansa BS. Is there an advantage in onset of action with mixing lignocaine and bupivacaine? J Plast Reconstr Aesthet Surg. 2017 Dec;70(12):1782. doi: 10.1016/j.bjps.2017.06.009. Epub 2017 Jun 26. PMID: 28698059.
5.    Almasi R, Rezman B, Kriszta Z, et al. Onset times and duration of analgesic effect of various concentrations of local anesthetic solutions in standardized volume used for brachial plexus blocks. Heliyon. 2020 Sep 2;6(9):e04718. doi: 10.1016/j.heliyon.2020.e04718. PMID: 32944664; PMCID: PMC7481523.
6.    Taylor A, McLeod G. Basic pharmacology of local anaesthetics. BJA Educ. 2020 Feb;20(2):34-41. doi: 10.1016/j.bjae.2019.10.002. Epub 2019 Dec 4. Erratum in: BJA Educ. 2020 Apr;20(4):140. PMID: 33456928; PMCID: PMC7808030.
7.    Chu CR, Izzo NJ, Coyle CH, Papas NE, Logar A. The in vitro effects of bupivacaine on articular chondrocytes. J Bone Joint Surg Br. 2008 Jun;90(6):814-20. doi: 10.1302/0301-620X.90B6.20079. PMID: 18539679; PMCID: PMC6548455.
8.    Karpie JC, Chu CR. Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med. 2007 Oct;35(10):1621-7. doi: 10.1177/0363546507304719. Epub 2007 Jul 30. PMID: 17664340.
9.    Piper SL, Kim HT. Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am. 2008 May;90(5):986-91. doi: 10.2106/JBJS.G.01033. PMID: 18451389.
10. Dragoo JL, Korotkova T, Kanwar R, et al. The effect of local anesthetics administered via pain pump on chondrocyte viability. Am J Sports Med. 2008 Aug;36(8):1484-8. doi: 10.1177/0363546508318190. PMID: 18658020.
11. Gomoll AH, Kang RW, Williams JM, Bach BR, Cole BJ. Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy. 2006 Aug;22(8):813-9. doi: 10.1016/j.arthro.2006.06.006. PMID: 16904576.
12. Hansen BP, Beck CL, Beck EP, et al Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007 Oct;35(10):1628-34. doi: 10.1177/0363546507304136. Epub 2007 Jul 3. PMID: 17609526.
13. Webb ST, Ghosh S. Intra-articular bupivacaine: potentially chondrotoxic? Br J Anaesth. 2009 Apr;102(4):439-41. doi: 10.1093/bja/aep036. PMID: 19286766.
14. Kreuz PC, Steinwachs M, Angele P. Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature. Knee Surg Sports Traumatol Arthrosc. 2018 Mar;26(3):819-830. doi: 10.1007/s00167-017-4470-5. Epub 2017 Mar 13. PMID: 28289821.
15. Breu A, Rosenmeier K, Kujat R, et al. The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage. Anesth Analg. 2013 Aug;117(2):514-22. doi: 10.1213/ANE.0b013e31829481ed. Epub 2013 Jun 7. PMID: 23749443.
16. Hussain N, Brull R, Sheehy B, et al. Perineural liposomal bupivacaine is not superior to nonliposomal bupivacaine for peripheral nerve block analgesia. Anesthesiology. 2021 Feb 1;134(2):147-164. doi: 10.1097/ALN.0000000000003651. PMID: 33372953.
17. Hamilton TW, Athanassoglou V, Mellon S,et al. Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev. 2017 Feb 1;2(2):CD011419. doi: 10.1002/14651858.CD011419.pub2. PMID: 28146271; PMCID: PMC6464293.

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