Reevaluating the epinephrine myth: A comprehensive review

Abstract

The combination of local anesthetic drugs with epinephrine has conventionally been contraindicated in acral regions due to concerns of potential necrosis caused by compromised blood flow. However, this belief has been challenged since 2001, when studies demonstrated the safety and effectiveness of the combination. This review aims to analyze reported cases of acral area necrosis following the use of local anesthesia with epinephrine since 2001. A thorough search was conducted on PubMed and Google Scholar using specific keywords to identify articles reporting acral area necrosis caused using local anesthesia and epinephrine. Our search yielded eight publications describing a total of 13 cases of ischemic events in acral areas. These cases involved finger necrosis (five cases), scrotal skin necrosis (two cases), and eyelid necrosis (six cases), following the injection of a combination of epinephrine and lignocaine. The majority of affected patients were female who underwent surgical intervention and reconstruction. The use of epinephrine in local anesthesia offers significant advantages and is generally safe for acral areas. However, the risk of necrosis cannot be entirely eliminated, particularly in patients with compromised vascular function. Adhering to proper guidelines and selecting suitable patients can help mitigate the risk. Phentolamine serves as a potential rescue agent if vascular compromise occurs. Precautionary measures must be taken when using this combination in high-risk patients.

Introduction

Local anesthesia has been a crucial tool for surgeons for over a century, offering versatility in various soft-tissue and bony procedures. The integration of a vasoconstrictor, like epinephrine, into an anesthetic drug has greatly improved the surgical experience for both surgeons and patients. The use of local anesthesia combined with a vasoconstrictor was initially documented in 1903.[1] However, concerns about the potential risk of necrosis in acral areas have cast doubt on its application in these regions. The widely taught medical dictum “Never inject epinephrine into fingers, toes, nose, pinna, and penis” reinforces this skepticism.[2,3,4,5,6,7]

In recent decades, there has been a notable increase in the utilization of the lidocaine–epinephrine combination in hand surgeries. A pivotal review article by Denkler in 2001[8] played a significant role in shifting the perception of this combination. Consequently, numerous studies have emerged advocating for its use across various surgical specialties. Our review article aims to investigate the reported cases of acral area ischemia since 2001 and explore the direct association with epinephrine, if any.

Materials and Methods

An in-depth analysis of the medical literature since 2001 was performed, encompassing case reports, reviews, and clinical trials involving the administration of epinephrine with local anesthesia in acral areas. A thorough search was performed on PubMed and Google Scholar using the keywords: epinephrine, local anesthesia, necrosis, fingers, ears, eyelids, and penis. Our search yielded eight publications that documented cases of acral area necrosis following the injection of a combination of lidocaine and epinephrine.

Results

Since the popularization of lidocaine as the preferred local anesthetic in 1948, only a small number of case reports have described ischemic events in acral areas following the injection of a lidocaine–epinephrine combination. Our review identified a total of 13 published cases of acral area ischemic events since 2001, as summarized in Table 1.

Table 1.

The reports of acral necrosis associated with the use of lidocaine and adrenaline since 2001

Year of publication	Author(s)	Number of cases	Age (years)/sex	Comorbidities	Area affected	Route of administration	Dosage	Procedure	Ischemic events	Outcome
2010	Mili-Boussen et al.[14]	2	74/female 81/female	None	Eyelid	Local infiltration	2% lidocaine + 1: 100,000 epinephrine	Lacrimal sac surgery	Necrosis	Healed by eschar formation
2011	Yakoubi et al.[15]	3	50/female 67/female 36/male	None	Eyelids	Local infiltration	2% lidocaine + 1: 100,000 epinephrine	Eyelid repair	Necrosis	Surgical debridement
2011	Yakoubi et al.[15]	1	5/female	None	Eyelids	Local infiltration	2% lidocaine + 1: 100,000 epinephrine	Temporal artery biopsy	Necrosis	Surgical debridement
2012	Ravindran and Rajendran[9]	1	19/female	Raynaud’s phenomenon	Finger	Ring block	1% lidocaine + 1: 100,000 epinephrine	Incision and drainage	Necrosis	Dry gangrene
2014	Ruiter et al.[10]	1	16/female	None	Finger	Ring block	Not mentioned	Wart excision	Necrosis	Amputation
2015	Hutting et al.[11]	1	70/female	Diabetes mellitus, atherosclerosis	Finger	Local infiltration	1% lidocaine + 1: 100,000 epinephrine	Trigger finger release	Gangrene	Surgical debridement
2015	Gul et al.[16]	2	2/male 1/male	None	Scrotum	Ring block penis	1% lidocaine + 1: 100,000 epinephrine	Circumcision	Necrosis	Soft-tissue reconstruction
2016	Zhang et al.[12]	1	63/female	Chronic smoker	Finger	Local infiltration	1% lidocaine + 1: 100,000 epinephrine	Trigger finger release	Gangrene	Amputation
2017	Zhu et al.[13]	1	65/female	Raynaud’s phenomenon, coronary artery disease	Finger	Local infiltration	1% lidocaine + 0.25% bupivacaine + 1: 100,000 epinephrine	Carpal tunnel syndrome and trigger finger release	Delayed ischemic change	Recovered completely by phentolamine rescue

In 2012, Ravindran and Rajendran[9] described a case of fingertip necrosis in a 19-year-old female who underwent surgical drainage for paronychia. The procedure involved an infiltration of a lidocaine–epinephrine combination (1% lidocaine–1:100,000 epinephrine). She had undiagnosed Raynaud’s phenomenon, and necrosis occurred 4 days after the procedure, progressing to dry gangrene. The condition eventually healed with conservative measures, and no phentolamine, a reversal agent, was used.

In 2014, Ruiter et al.[10] documented a case of a 16-year-old otherwise healthy girl who underwent surgical excision of a wart. A digital block with lidocaine and epinephrine was administered at the level of the middle phalanx, although the specific concentration and dose of epinephrine were not specified. The finger subsequently displayed signs of devascularization and necrosis over several days. The patient required surgical debridement and amputation. The authors expressed uncertainty regarding the direct attribution of the necrosis to epinephrine, but they noted that the timely administration of phentolamine could have potentially prevented the necrotic outcome.

In 2015, Hutting et al.[11] described a case of digital necrosis in a 70-year-old woman with diabetes mellitus. The patient had undergone trigger finger release treatment with 1% lidocaine supplemented with 1:100,000 epinephrine. When ischemic symptoms developed, attempts were made to manage them with nadroparin (antithrombotic) and nifedipine (vasodilator). However, the patient ultimately progressed to gangrene. Further evaluation revealed severe atherosclerotic changes in the affected hand, suggesting underlying vascular pathology.

In 2017, Zhang et al.[12] presented a case involving a 63-year-old female, a chronic smoker, who experienced necrosis in three digits following the injection of a lidocaine–epinephrine combination (1% lidocaine and 1:100,000 epinephrine) at the subcutaneous fat and flexor sheath levels of the middle three fingers for the treatment of trigger finger. Due to a time delay of almost 24 h after surgery when she presented with fingertip blisters and evidence of tissue necrosis, phentolamine rescue was not attempted. The patient ultimately underwent amputation, which resulted in uneventful healing.

In 2017, Zhu et al.[13] reported a case of delayed ischemic signs in a finger following the administration of local anesthesia with epinephrine. The patient, a 65-year-old nonsmoker female with preexisting coronary artery disease, underwent release of the transverse carpal ligament and A1 pulley in the right hand. The surgical sites received a subcutaneous injection of 10 ml of 1% lidocaine and 10 ml of 0.25% bupivacaine added with 1:100,000 epinephrine. Although the patient was discharged 2 h after observing pink fingers, she returned 10 h postsurgery with a dusky, cold, and clammy middle finger. The finger was successfully revived after 1.5 h with an injection of 1.5 mg of phentolamine combined with 1 ml of 2% lidocaine at the base of the middle finger. The ischemia developed 2.5 h after the initial event and lasted even at the 10-h mark. This event can likely be attributed to the volume of the injection (8 ml at the level of the A1 pulley) and the cold weather conditions at the time, which may have induced a vasospastic response.

In 2010, Mili-Boussen et al.[14] reported two cases of eyelid necrosis occurring after lacrimal sac surgery, where a combination of 3 ml of 2% lignocaine with 1/100,000 epinephrine injection into the medial canthal region was used. Yakoubi et al.[15] documented four cases of eyelid necrosis in 2011. Three cases resulted from eyelid laceration repair, while one case followed a temporal artery biopsy. All cases developed secondary bacterial infections and tissue loss, which required surgical debridement and reconstruction.

In 2015, Gul et al.[16] from Turkey documented two cases of scrotal necrosis in children following subcutaneous ring block at the midshaft penis level for circumcision. The procedure utilized 1% lidocaine with 1:200,000 epinephrine. Both children presented with scrotal skin necrosis on the 5^th and 4^th postoperative days, respectively, and required surgical wound debridement. The authors attributed the necrotic outcomes to epinephrine in both cases.

Discussion

Epinephrine has been widely used as an adjunct to local anesthesia for more than a century due to its vasoconstrictive properties. Acting on alpha-1 and alpha-2 adrenergic receptors, epinephrine causes constriction of small blood vessels, enhancing the effects of local anesthesia by delaying its absorption. Its combination with local anesthetics was first introduced by Braun in 1903, when he added it to cocaine, referring to the mixture as a “chemical tourniquet.”[1] The benefits of combining epinephrine with local anesthesia are significant, including faster onset and longer duration of anesthesia, delayed systemic absorption, reduced toxicity, and the ability to use a higher volume of anesthetic while maintaining a bloodless surgical field.

The introduction of lidocaine in the 1940s revolutionized local anesthesia. Compared to the previously popular procaine, lidocaine offered advantages such as a longer duration of action and easier preparation. Procaine, an ester-based anesthetic, required fresh preparation with epinephrine before use, leading to longer preparation times and unstable solutions.[17] Since 1948, the lidocaine–epinephrine combination has become the most commonly used formulation, with lidocaine concentrations ranging from 0.5% to 2% and epinephrine concentrations ranging from 1:80,000 to 1:1,000,000. The recommended maximum safe dose of lidocaine when used with a vasoconstrictor is 7 mg/kg.[18,19] However, higher doses up to 35 mg/kg have been tolerated well in procedures such as automated tumescent local anesthesia for liposuction and skin tumor excisions.[20]

The burning sensation experienced during lidocaine injection has been attributed to its acidic pH. Plain lidocaine (pH approximately 6) becomes more acidic when supplemented with epinephrine (pH approximately 4). To establish a tissue pH of 7.3–7.6, it is recommended to mix 1 ml of 8.4% sodium bicarbonate with 10 ml of 1% lidocaine and 1:100,000 epinephrine. Sodium bicarbonate neutralizes the acidity, alleviating the burning sensation.[21,22,23] Complete restoration of vascularity typically takes around 30 min following epinephrine injection.[24]

Phentolamine, an epinephrine reversal agent, was introduced in 1957.[25] As a short-acting, nonselective alpha-adrenergic receptor antagonist, phentolamine competitively inhibits the action of epinephrine, causing vasodilation. Phentolamine can be administered in doses of 1–2 mg diluted in 1–5 ml of normal saline at sites where epinephrine has been instilled. Reversal of vasoconstriction usually occurs within approximately 85 min.[26] Care should be taken to use small volumes to avoid compromising blood flow further. Multiple injections may be required due to its short duration of action (20–30 min).[27] Successful reversal resulting in restoration of circulation has been reported even with significant time delays of up to 13 h. Although there are potential risks of hypotension (due to peripheral vasodilation) and tachycardia with the use of phentolamine, no severe adverse effects have been reported.[28]

The Surgical Tradition Revisited: Epinephrine in the Acral Areas

Despite concerns and reservations expressed in various textbooks, studies have provided evidence supporting the safe use of epinephrine in acral areas such as the fingers, toes, ears, nose, eyelids, and penis. The first significant study in this regard was conducted by Steinberg and Block in 1971, where they observed no cases of necrosis or gangrene in over 200,000 patients undergoing forefoot and toe surgeries with the combination of local anesthesia and epinephrine (1:100,000–1:200,000).[29]

In 2001, Denkler conducted a comprehensive review of the literature on digital necrosis following local anesthesia and found only 48 reported cases worldwide over 120 years, with epinephrine implicated in 21 cases. Various factors were identified as potential causes, such as unstandardized preparation, larger volumes, postoperative hot soaks, inappropriate tourniquet application, and infection. Interestingly, almost all the reported cases were associated with procaine, a few with cocaine, and a few with unknown drug, but not with lidocaine and epinephrine.[8,30]

A review by Krunic et al. highlighted the inadequately documented nature of most reports on finger necrosis, often lacking details such as the actual dose or the route of epinephrine administration.[31]

In 2005, a large multicenter prospective study published by Lalonde et al. reported no cases of ischemia in patients who underwent hand surgeries using the combination of bupivacaine or lidocaine with epinephrine in ratios of 1:100,000 or less.[32] Similarly, a retrospective study by Firoz et al. in 2009, involving 63 cases of Mohs micrographic surgery for skin tumors, found no instances of digital necrosis.[33] However, it is worth noting that this study focused on infiltration anesthesia at the tumor site rather than digital block and hence may be biased.

Subsequent studies by Sardenberg et al. in 2018 and Lalchandani et al. in 2019 further supported the safe outcomes of hand surgeries with local anesthesia and epinephrine combination, with no recorded cases of digital necrosis.[34,35]

The presence of protective mechanisms in digits, such as vasodilator beta-adrenergic receptors or transient hyperemic responses, has been proposed to explain the prevention of total ischemia in these areas.[36,37] Studies by Sönmez et al. in 2008 and Green et al. in 1992 demonstrated that even during maximal vasoconstriction induced by epinephrine, digital perfusion is not completely interrupted, and circulation is maintained.[38,39] These findings challenge the notion of irreversible vasoconstriction caused by epinephrine in digits.

Regarding the usage of epinephrine in the nose and ears, limited studies have been conducted. However, a study by Häfner et al. in 2004 reported no significant necrosis of the ear, nose, or flaps in over 10,000 cases using epinephrine-supplemented lidocaine for skin tumor removal and flap surgeries. The study included patients with medical comorbidities such as diabetes mellitus, coronary artery disease, and hypertension, indicating that epinephrine supplementation did not introduce complications in these individuals and may even enhance tissue healing by reducing the need for electrocautery.[40]

In a retrospective analysis carried out by Schnabl et al. in 2014, the use of local anesthesia with epinephrine in penile root block for circumcision was found to be safe. They studied 95 patients ranging in age from 3 to 87 years and reported no cases of necrosis. The authors reviewed the vascular anatomy of the penis, highlighting its highly vascular nature with rich anastomosis and no end arteries, which supports the safety of subcutaneous infiltration anesthesia with the lidocaine–ropivacaine–epinephrine combination.[41]

In a comparative research conducted by Alizadeh et al. in 2016, the use of diluted epinephrine (1:100,000) for hemostasis in hypospadias surgery was found to be safe and effective in controlling blood loss. The study reported favorable outcomes with epinephrine injection.[42]

A survey conducted in 2017 among dermatologists and venereologists in the United Kingdom by Wernham and Shim focused on the technique of penile biopsy, the use of epinephrine during the procedure, and the complications noted. None of the physicians who responded reported penile necrosis after the injection of epinephrine. It is important to note that the response rate in the survey was limited to 4.4% of the concerned physicians, making it a relatively small sample size.[43]

Regarding accidental injections of 1:1000 epinephrine, which is available in auto-injector pens for the treatment of acute anaphylactic reactions, numerous cases have been reported since 1989.[44] Despite concerns about irreversible vasoconstriction and ischemia, no incidents of digital necrosis have been documented. Fitzcharles-Bowe et al., researchers in the field, have personally injected high doses of epinephrine in their fingers and have shown the spontaneous reversal of effects without any intervention. Treatment options for accidental injections include conservative measures such as warm soaks, topical nitroglycerin paste, and digital block with phentolamine.[45]

The safety record of lidocaine–epinephrine combination in over half a million reported operations on the acral areas without resulting necrosis further supports the conclusion that epinephrine is safe to be injected in these areas. In cases where vascular compromise is suspected, it can be safely reversed with phentolamine.[46] This ability to use local anesthetic with epinephrine in the acral areas has significant therapeutic implications, making hand surgeries easier, more cost-effective, and safer. The avoidance of tourniquets and reduced dependence on sedation/anesthesia also benefit the patients.[44]

Several critical considerations must be taken into account during the drug design process for compounds intended for combination with epinephrine, as outlined in Table 2. To assist researchers in addressing these factors, a variety of pharmacokinetic tools [Table 3] and docking softwares [Table 4] are accessible, facilitating comprehensive investigations in this domain. Furthermore, a deeper understanding of the physicochemical, pharmacokinetic, and receptor functions of epinephrine can be quite useful in this regard [Table 5].

Table 2.

Points to be remembered about epinephrine while designing new drugs

Effect	Comments
Dosage and concentration	Very high concentration can lead to adverse effects such as tachycardia, hypertension, and anxiety.
Cardiovascular effects	Stimulation of beta-1 adrenergic receptors in the heart increases the heart rate and force of contraction It can also cause vasoconstriction, leading to increased blood pressure.
Respiratory effects	Epinephrine can dilate the airways by acting on beta-2 adrenergic receptors. However, excessive use can lead to bronchoconstriction, so balancing these effects is important.
Vasoconstriction and blood flow	Epinephrine’s vasoconstrictive effects can impact blood flow to different organs and tissues. Its effect on oxygen and nutrient delivery has to be considered when designing drugs.
Anxiety and nervous system effects	Epinephrine can induce feelings of anxiety, restlessness, and even tremors. These effects need to be carefully managed, especially in drugs intended for systemic use.
Metabolic effects	Epinephrine can increase blood glucose levels by promoting glycogen breakdown. This effect can be useful in certain medical situations but can also lead to hyperglycemia if not controlled.
Drug interactions	Epinephrine can interact with a variety of other medications. When designing new drugs, it is crucial to consider potential interactions that could amplify or negate the effects of epinephrine.
Delivery mechanism	The most appropriate delivery mechanism for the drug has to be considered. Epinephrine can be administered through injection, inhalation, or topical application, each with its own set of considerations and challenges.
Targeted applications	The specific medical conditions the new drug aims to address and how epinephrine’s properties can be harnessed to achieve the desired therapeutic outcomes have to be determined.
Side effects and adverse reactions	Potential side effects and adverse reactions associated with the use of epinephrine have to be carefully assessed. This includes monitoring for allergic reactions, arrhythmias, and hypertensive crises.
Regulatory approval	Epinephrine is a controlled substance, and drugs involving its use may require regulatory approval. Compliance with regulatory agencies and guidelines has to be ensured.
Demographics of the patient population	Sensitivity to epinephrine can vary among individuals, so dosage adjustments might be necessary.

Table 3.

Some pharmacokinetic and pharmacodynamic software tools available for predicting drug interactions and receptor actions

Software	Function	Use
SwissADME	Supports drug discovery	To evaluate the pharmacokinetics, drug-likeness, and medicinal chemistry-friendliness of minute molecules
GastroPlus® PBBM/PBPK	Focuses on predicting oral drug absorption, pharmacokinetics, and pharmacodynamics	To study the impact of formulation changes, food effects, and drug interactions on drug behavior
Simcyp™ PBPK simulator	It simulates the ADME processes of drugs in various populations	For dosing, clinical study design optimization, evaluation of new drug formulations, dose setting in untested populations, performing virtual bioequivalence analyses, and drug–drug interaction prediction
PK-SIM® AND MOBI® FOR PBPK	PK-Sim is the software for modeling and simulating physiological and pharmacokinetic processes. MoBi is a complementary tool that focuses on graphical modeling of pharmacodynamics	To simulate the entire drug development process, including drug interactions and receptor actions
ADMET Predictor®	Predicts various ADME properties of drugs, including absorption, distribution, metabolism, and excretion	Provides utility for data analysis, metabolism prediction, and AI-driven drug design
MedChem Studio™	Advanced cheminformatics platform for lead identification, data mining, and drug design It is a module in ADMET Predictor®	For drug discovery, lead identification, de novo design, scaffold hopping, and lead optimization
DILIsym®	For predicting drug-induced liver injury	While its main focus is on hepatotoxicity, it also considers drug interactions and receptor actions that may contribute to adverse effects
ACD/Percepta (ACD, Inc., Pharma Algorithms, Inc.)	Comprehensive tools for the prediction of basic physicochemical properties, ADME, and toxicity endpoints	By reviewing chemicals that are similar to the target from the training set, along with literature data and references, it enables the evaluation of the prediction’s consistency
NONMEM	It is especially powerful in the context of population pharmacokinetics, pharmacometrics, and pharmacokinetic/pharmacodynamic models	Helps modelers maintain their files, track the progress of their models, and perform goodness-of-fit tests

ADME=Absorption, distribution, metabolism, and excretion, DILI=Drug-induced liver injury, ADMET=Absorption, distribution, metabolism, excretion, and toxicity, AI=Artificial intelligence, PBBM/PBPK=Physiologically Based Biopharmaceutics Modeling/Physiologically Based Biopharmaceutics Modeling, NONMEM=Nonlinear mixed-effects modeling, ACD=Advanced Chemistry Development

Table 4.

Some molecular docking software tools that are used to predict how drugs interact with receptors and proteins

Software	Uses
AutoDock	Molecular modeling simulation software
AutoDock Vina	Faster than AutoDock with improved accuracy
iGEMDOCK	For understanding the ligand-binding mechanisms and discovering lead compounds
Molegro Virtual Docker	Protein–ligand docking simulation program that helps in docking simulations in a fully integrated computational package
Schrodinger Suite	Virtual screening software for computational drug discovery
MOE	Combines method development, modeling, and visualization into a single package
PyRx	To check libraries of compounds against possible therapeutic targets
Gold	Explores the complete spectrum of ligand conformational flexibility with partial flexibility of the protein
FlexX	A high-throughput, structure-based virtual screening
HADDOCK	Information-based flexible docking approach
CDOCKER	MD simulated-annealing-based algorithm

MD=Molecular dynamics, MOE=Molecular Operating Environment, HADDOCK=High Ambiguity Driven biomolecular DOCKing, Gold=Genetic Optimization for Ligand Docking

Table 5.

Properties of epinephrine[47,48]

Molecular formula	C9H13NO3
Physical structure	Microcrystalline powder or granules
Color	White - changes to brown on exposure to light
Odor	None
Taste	Bitter, numbing
Melting point	211.5°C
Solubility	Insoluble in ethanol; soluble in acetic acid
Plasma half-life	2–3 min
Site of production	Adrenal medulla
Site of metabolism	Liver
Enzymes involved in metabolism	COMT and MAO
Metabolic products	Metanephrine and 3-methoxy-4-hydroxymandelic acid, VMA
Receptors	Adrenergic receptors
	Alpha-1: Alpha-1A, alpha-1B, alpha-1D
	Alpha-2: Alpha-2A, alpha-2B, alpha-2C
	Beta: Beta-1, beta-2, beta-3
	Adrenaline acts specifically on
	Alpha-1 receptors
	Increased vascular smooth muscle contraction
	Pupillary dilator muscle contraction
	Vasoconstriction
	Intestinal sphincter muscle contraction
	Beta-1 receptors
	Increased heart rate
	Increased myocardial contractility
	Renin release
	Beta-2 receptors
	Bronchodilation
	Peripheral vasodilation
	Increased aqueous humor production
Site of excretion	Kidneys

COMT=Catechol-O-methyltransferase, MAO=Monoamine oxidase, VMA=Vanillylmandelic acid

Recommendations

To summarize the recommendations and considerations for the safe administration of lidocaine with epinephrine in the acral areas:

1. The usage of 2% lidocaine (7 mg/kg) with epinephrine (1:100,000 or less) is considered safe for the acral areas.

2. The injection should be given along the subcutaneous fat in the base of fingers or along the mid phalanx using the WALANT technique proposed by Lalonde et al.[49] Digital nerves and tendon sheaths should be avoided.

3. Adequate vasoconstriction should be allowed by waiting for a minimum of 30 min before starting the surgery.

4. Patients should be monitored for a minimum duration of 6 h to ensure the return of perfusion.

5. In case of persistent vascular compromise, injection of phentolamine at the sites of epinephrine injection should be considered. Multiple doses may be necessary, and administration should be done under cardiac monitoring.

6. Patient selection is crucial for successful administration. High-risk patients with conditions such as diabetes, peripheral occlusive vascular disease, Raynaud’s phenomenon, prior digit reimplantation, a history of tissue necrosis, or smokers should be avoided.

While the combination of local anesthetic and epinephrine has shown success in a majority of cases and has broader indications in different areas, there is still a risk of necrosis in the acral areas. Surgeons should exercise caution, especially when treating high-risk patients, to prevent potential legal issues. Although the legal implications of acral necrosis following the use of epinephrine in such areas are not clearly defined, the safe usage of the combination as supported by recent literature and textbooks provides legal validity. Nonetheless, appropriate precautions should be taken in the high-risk populations mentioned above.[49,50,51,52]

Conclusion

Surgeries in the acral areas, including fingers, toes, ears, nose, and penis, can generally be safely performed under local anesthesia with epinephrine supplementation. There is no evidence of digital necrosis directly caused by epinephrine, whether in digital nerve blocks (at concentrations of 1:80,000 or less) or accidental high-dose injections (at a concentration of 1:1000). The risk of complications in patients with preexisting poor circulation is uncertain and lacks definitive scientific evidence. Proper patient selection and careful injection techniques are crucial for successful local anesthesia administration. Precautionary measures should be taken when using local anesthesia with epinephrine in high-risk patients. Familiarity with the pharmacokinetics of phentolamine can prove advantageous in managing vascular compromise should it arise.

Overall, while the use of local anesthesia with epinephrine in acral areas is generally safe, caution and appropriate measures should be taken to ensure patient safety, especially in high-risk cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.