Is It True That Epinephrine Can Cause Necrosis in Areas of End-Arterial Circulation?

“Fingers, toes, ears, and nose are places where epinephrine never goes.” That is an adage I heard during podiatry school, my clerkships, and from various attendings throughout my training. The theory is that those are end-arterial circulation areas and epinephrine could cause necrosis by sudden vasoconstriction. The idea makes sense, which is likely why the concept has persisted in emergency medicine, orthopedics, and podiatry.

However, as I will discuss, this has been proven a myth time and time again. I have observed epinephrine’s continued use in end-arterial circulation areas at many levels and in many geographic areas.

The theory is based on preclinical science, but once you dive deeper into the literature, nothing holds up. There have been many studies with hundreds of thousands of patients who have undergone injections with epinephrine into their digits without issue.¹

Let’s look at why this myth took hold. Before the standardization of local anesthetic with epinephrine (typically with concentrations of 1:100,000 or 1:200,000), Heinrich Braun, MD, in 1903 pioneered the “pharmacological tourniquet,” which consisted of cocaine mixed with epinephrine.² Doctors replaced cocaine with procaine shortly after. Due to the inadequate measuring capabilities of that time, physicians would manually titrate their concoction by estimating the number of drops of epinephrine just prior to use, leading to large inconsistencies with their injectables.²

In a literature review from 1880–2000, there were only 48 reported patients who received epinephrine and/or procaine who developed digital necrosis, all prior to the 1950s.² Twenty-one of these patients had epinephrine mixed with procaine, while the remaining 27 consisted of procaine alone. Due to the fact that there were more cases of necrosis solely with procaine, the United States Food and Drug Administration (FDA) performed an investigation. The FDA found procaine was the agent responsible for the ischemia because of its low pH, which became more acidic as it aged, with some vials found to have a pH of 1.^3,4

The data regarding epinephrine’s effect on transient vasoconstriction and reduction in blood flow is very clear. Multiple studies using a variety of methods determined that while there is a temporary decrease in blood flow, it typically returns to normal after 48–180 minutes.^5-7 Somnez and colleagues showed that compared to plain anesthetic, epinephrine did not alter capillary blood gas values, but did prolong the hypoesthesia by three hours.⁸ Hafner and team showed a decrease in digital perfusion levels with epinephrine using laser Doppler flowmetry. This was reversed after 24 minutes and the vasoconstrictive effect was undetectable 48 minutes later.⁵ Schnabl compared skin perfusion of fingers utilizing anesthetic with a tourniquet versus local with epinephrine and the levels were similar; however, there were more complications in the tourniquet group.⁹

The literature has demonstrated time and time again that these injections are safe and have significant benefits compared to plain local anesthesia (with tourniquet). Steinberg and Block performed a comprehensive literature review with over 260,000 injections of lidocaine with epinephrine, with many given into the toes and forefoot.¹ There were no reports of necrosis or tissue damage. Since the commercial introduction of lidocaine with epinephrine in 1948, there have been zero case reports of digital gangrene in the toes, and one in the middle finger in 2014. In the single case report of necrosis of the middle finger, the authors had no explanation for the necrosis, but postulated it could have been from hot water immersion. They also noted that use of phentolamine as a rescue agent could have saved that patient’s finger.^2,10

Denkler evaluated the treatment of Dupuytren’s contracture with plain versus local anesthetic with epinephrine and found no difference in rate of complications and no cases of digital necrosis or signs of ischemia during any of the procedures.¹¹ Andrades and colleagues evaluated patients in the emergency department who had digital lesions and compared plain versus local anesthetic with epinephrine. They found the epinephrine group needed significantly fewer injections, less local anesthetic, experienced a longer lasting effect, and related decreased pain visual analog scores (VAS).¹²

As previously mentioned, the typical concentration of epinephrine used in digital blocks is 1:100,000 or 1:200,000. Even accidental injections with a very high concentration of epinephrine (1:1,000), found in EpiPen^Ⓡ autoinjectors, have been documented with no cases of necrosis. There are hundreds of instances of auto-injections into thumbs and fingers in the literature.^13-15 There were no cases of necrosis in any of these, and only approximately 25 percent of patients received any pharmacological intervention.

Lastly, while epinephrine does theoretically pose some risk, when used it offers significant benefits as well. It is important to understand that tourniquets are not without untoward reactions. There are multiple reports of digital necrosis from use of tourniquets, usually due to failure to remove tourniquets after the procedure.^16-19 Altinyazar in 2010 found that in ingrown nail procedures, patients who received 2% lidocaine with 1:100,000 epinephrine (versus plain 2% lidocaine) took about 8 fewer days to heal peripheral tissue and alleviate drainage.²⁰ There was also significantly less anesthetic needed, which can alleviate volume-related concerns.

Similarly, Cordoba-Fernández and colleagues compared plain mepivacaine with tourniquet and mepivacaine with 1:100,000 epinephrine, and the addition of epinephrine caused significantly less bleeding and a greater anesthetic effect.²¹ Problems with tourniquets include significant reactive hyperemia, which can lead to a diminished anesthetic effect, hematoma formation, nerve or vessel damage, and edema due to lymphatic obstruction. Tourniquets are not without risks including potential muscle, vessel, or nerve injury, risks of using systemic anesthesia, necrosis, reperfusion injuries, and requiring increased amounts of local anesthesia.¹⁹

Evidence-based medicine should be the cornerstone of practice, and this topic is a good example of following dogma that has been disproven in many instances. Although local anesthetic with epinephrine is likely not right for every patient, I think it is important to teach future generations of physicians that it is a viable option with and there are hundreds of thousands of cases in the literature supporting epinephrine’s safety.

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.

Disclaimer: The views and opinions expressed are those of the author(s) and do not necessarily reflect the official policy or position of Podiatry Today or HMP Global, their employees and affiliates. Any content provided by our bloggers or authors are of their opinion and are not intended to malign any religion, ethnic group, club, association, organization, company, individual, anyone or anything.

References

1)    Steinberg MD, Block P. The use and abuse of epinephrine in local anesthetics. J Am Podiatry Assoc. 1971; 61(9):341–343.

2)    Denkler K. A comprehensive review of epinephrine in the finger: to do or not to do. Plast Reconstr Surg. 2001;108(1):114-124. doi: 10.1097/00006534-200107000-00017. PMID: 11420511.

3)    Food and Drug Administration. Warning--procaine solution. JAMA. 1948;138:599.

4)    Thomson CJ, Lalonde DH, Denkler KA, Feicht AJ. A critical look at the evidence for and against elective epinephrine use in the finger. Plast Reconstr Surg. 2007;119(1):260-266. doi: 10.1097/01.prs.0000237039.71227.11. PMID: 17255681.

5)    Hafner HM, Schmid U, Moehrle M, Strolin A, Breuninger H. Changes in acral blood flux under local application of ropivacaine and lidocaine with and without an adrenaline additive: A double-blind, randomized, placebo-controlled study. Clin Hemorheology and Microcirc. 2008;38:279-288.

6)    Altinyazar HC, Ozdemir H, Koca R, Hoşnuter M, Demirel CB, Gündoğdu S. Epinephrine in digital block: color Doppler flow imaging. Dermatol Surg. 2004;30(4 Pt 1):508-511. doi: 10.1111/j.1524-4725.2004.30165.x. PMID: 15056139.

7)    Denkler KA. Epinephrine in the digits. Plast Reconstr Surg. 2011;128(2):598-599. doi: 10.1097/PRS.0b013e31821eef8f. PMID: 21788871.

8)    Sönmez A, Yaman M, Ersoy B, Numanodlu A. Digital blocks with and without adrenalin: a randomised-controlled study of capillary blood parameters. J Hand Surg Eur Vol. 2008;33(4):515-8. doi: 10.1177/1753193408090143. PMID: 18687842.

9)    Schnabl S, Unglaub F, Leitz Z, Breuninger H, Hafner HM. Skin perfusion and pain evaluation with different local anesthetics in a double blind randomized study following digital nerve block anesthesia. Clin Hemorheology Microcirc. 2013;55:241-253.

10) Ruiter T, Harter T, Miladore N, Neafus A, Kasdan M. Finger amputation after injection with lidocaine and epinephrine. Eplasty. 2014;14:ic43. PMID: 25404956; PMCID: PMC4226048.

11) Denkler K. Dupuytren's fasciectomies in 60 consecutive digits using lidocaine with epinephrine and no tourniquet. Plast Reconstr Surg. 2005;115(3):802-810. doi: 10.1097/01.prs.0000152420.64842.b6. PMID: 15731682.

12) Andrades PR, Olguin FA, Calderón W. Digital blocks with or without epinephrine. Plast Reconstr Surg. 2003;111(5):1769-1770. doi: 10.1097/00006534-200304150-00040. PMID: 12655238.

13) Muck AE, Bebarta VS, Borys DJ, Morgan DL: Six years of epinephrine digital injections: Absence of significant local or systemic effects. Ann Emerg Med. 2010;56:270-274,

14) Fitzcharles-Bowe C, Denkler K, Lalonde D: Finger injection with high-dose (1:1,000) epinephrine: Does it cause finger necrosis and should it be treated? Hand (NY). 2007;2:5-11

15) Mrvos R, Anderson BD, Krenzelok EP. Accidental injection of epinephrine from an autoinjector: Invasive treatment not always required. South Med J. 2002; 95(3): 318-320.

16) Becerro de Bengoa Vallejo R, Losa Iglesias ME, López DL, Posada-Moreno P, López PP, Rodriguez MF, Crespo AS. Effects of digital tourniquet ischemia: a single center study. Dermatol Surg. 2013;39(4):584-592. doi: 10.1111/dsu.12115.  PMID: 23331994.

17) Pietiläinen S, Truong A, Bindra R. Case series of: Iatrogenic digital compression ischaemic injury in the emergency department. Am J Emerg Med. 2021;50:602-605. doi: 10.1016/j.ajem.2021.09.052. PMID: 34592568.

18) Manske C. Nothing called small surgery. Patient Safety Network. Available at:  https://psnet.ahrq.gov/web-mm/nothing-called-small-surgery . Accessed September 29, 2022.

19) Lahham S, Tu K, Ni M, Tran V, Lotfipour S, Anderson CL, Fox JC. Comparison of pressures applied by digital tourniquets in the emergency department. West J Emerg Med. 2011 May;12(2):242-9. PMID: 21691536; PMCID: PMC3099617.

20) Altinyazar HC, Demirel CB, Koca R, Hosnuter M. Digital block with and without epinephrine during chemical matricectomy with phenol. Dermatol Surg. 2010;36(10):1568-1571. doi: 10.1111/j.1524-4725.2010.01681.x. PMID: 20698866.

21) Córdoba-Fernández A, Rodríguez-Delgado FJ. Anaesthetic digital block with epinephrine vs. tourniquet in ingrown toenail surgery: a clinical trial on efficacy. J Eur Acad Dermatol Venereol. 2015;29(5):985-990. doi: 10.1111/jdv.12746. PMID: 25284453.