Accidental adrenaline auto-injector-induced digital ischaemia: a proposed treatment algorithm

Abstract

Increased numbers of adrenaline auto-injectors (AAIs) are in circulation in the UK. The rate of accidental auto-injection injuries has increased during this time. Various treatment strategies are described in the literature. We present the case of a 32-year-old, right-hand-dominant man who sustained an unintentional AAI injury to the volar aspect of his right thumb. On presentation to the emergency department, the thumb was ischaemic. There was no improvement with simple conservative measures (warm soaks). The patient was referred to our tertiary hand surgery service and a digital block using 2% lidocaine promoted reversal of ischaemia within 2 hours with no long-term sequelae. Phentolamine rescue, on standby, was not necessary in this case. In this case report, we highlight the therapeutic challenges associated with managing AAI injury and propose an evidence-based treatment algorithm to prevent risk of severe adverse outcomes such as digital necrosis.

Background

Adrenaline is used in the treatment of anaphylaxis. Adrenaline auto-injectors (AAIs) are preloaded medical devices that can be used to discharge high-dose adrenaline quickly, via the intramuscular route, to terminate acute anaphylaxis. There are three AAIs available in the UK market: Emerade (Pharmaswiss; Czech Republic) EpiPen (Mylan; UK) and Jext (ALK-Abello; UK).¹ Typically, the standard dosing of preloaded adrenaline (1:1000) is 0.3 mg in adults and 0.15 mg in children.² The number of AAI prescriptions has risen 355% in general practice in the UK between 2000 and 2012.³ This has been associated with an increase in the numbers of reported accidental or unintentional AAI injuries. Digits are the most commonly reported site of injury.⁴ Sequelae of accidental AAI injury include pain, paraesthesia and ischaemia and may ultimately lead to necrosis.⁵ There have been two reported cases of digital amputation following accidental AAI injury.⁶ There are a variety of proposed treatment strategies for accidental AAI injury in the literature including warm soaks, nitroglycerine and phentolamine administration.⁷ We aim to raise awareness of accidental AAI injury to digits and provide a treatment algorithm for their management.

Case presentation

A 32-year-old right-hand-dominant man was referred to our tertiary hand surgery service after accidental injection of adrenaline (0.3 mg, 1:1000) from an Epipen (Mylan; UK) into the pulp of his dominant thumb. The patient had a previous medical history of asthma and gastro-oesophageal reflux disease and had no known drug allergies. He was a nonsmoker. He presented with pain, paraesthesia and pallor to the affected thumb. Capillary refill was prolonged at 6 s and the thumb was cold to touch. Ecchymosis was noted at the site of injection (figure 1). He did not display any symptoms or signs of adverse systemic effects. In order to avoid digital necrosis, urgent reversal of adrenaline effect was attempted.

Figure 1.

Appearance of thumb following accidental AAI injury. AAI, adrenaline auto-injector.

Investigations

His baseline observations were within normal limits. An ECG was undertaken to ensure no cardiac side effects from the adrenaline—this showed normal sinus rhythm.

Treatment

Initial treatment included the application of warm soaks to the thumb for 20 min with no therapeutic effect. Topical nitroglycerine was then applied to the thumb pulp and further warming was initiated through use of a Bair Hugger device (3M, USA). After a further 30 min, the thumb showed minimal improvement with a persistently pale, cold digit and sluggish capillary refill time. Early consultation was made with the on-call toxicology team regarding phentolamine rescue. Meanwhile a digital block was administered with 5 mL of 2% lidocaine in standard fashion at the base of the thumb while acquiring phentolamine. Further assessment of the thumb 30 min after administration of lidocaine showed signs of reperfusion with the thumb now appearing pink in colour, warm to touch and with a capillary refill time of 2 s (figure 2). Pain reported by the patient had also improved indicating reversal of tissue ischaemia.

Figure 2.

Appearance of thumb following treatment with 2% lidocaine digital block and warming.

Outcome and follow-up

The patient was observed and the digit warmed with a Bair Hugger warming blanket for further 2 hours after lidocaine administration. The digit remained warm, pink and perfused with a capillary refill time of 2 s. Injection of phentolamine was not required in this instance, and after an adequate period of observation, the patient was discharged. On review at 48 hours postinjury, the thumb had remained perfused with no tissue necrosis (figure 3). He was discharged to his general practitioner and has not reattended for clinical review.

Figure 3.

Appearance of thumb 48 hours postaccidental AAI injury. AAI, adrenaline auto-injectors.

Discussion

A number of methods have been described to reverse the effects of AAI injuries in digits. Given that the half-life of adrenaline is 43 min±15 min,⁸ several case reports describe a purely conservative approach to manage without any intervention, with the assumption being that the effects of adrenaline would wear off prior to the onset of permanent ischaemic damage.^9–11 However, we would argue that the high concentration of adrenaline found in AAIs may result in a prolonged period of ischaemic time increasing the risk of digital necrosis. Moreover, there are a significant number of patients who experience symptoms such as severe pain and anxiety regarding loss of digit. We would, therefore, advocate prompt intervention.

There is currently no consensus on management of digital ischaemia secondary to adrenaline injection, although phentolamine has been suggested as the treatment of choice in a recent systematic review.⁷ Initial treatment with warm water has been shown ineffective in restoring digital perfusion and similar outcomes were encountered in the case presented here.⁷ Topical nitrate application has been shown to have limited beneficial effect.⁷

Phentolamine is a competitive α-receptor blocker and is used clinically in the management of hypertension, phaeochromocytoma and in hypertensive crises secondary to clonidine withdrawal.¹² Initial work by Zucker showed the potential of phentolamine as an agent to reverse the effects of adrenaline.¹³ Phentolamine use has also been demonstrated to have good effect in the treatment of catecholamine extravasation injuries in an attempt to limit local tissue necrosis.¹⁴ When phentolamine is required for rescue of digital ischaemia, it is administered at a dose of 0.45–2 mg subcutaneously at the site of injury.¹⁵ Terbutaline, which is a beta-2 agonist, has also been reported in the literature; however, this is not widely used and the efficacy of phentolamine when available is superior.¹⁶

The literature supports the utilisation of phentolamine as the gold standard in treatment of digital ischaemia induced by adrenaline and has been shown to reliably reverse vasoconstriction.^{7 15 17} Knowledge about the effects of adrenaline and the appropriate management of digital ischaemia has increased greatly in recent years due to the widespread adoption of wide awake local anaesthesia no tourniquet (WALANT) techniques in hand surgery.¹⁵ This involves infiltration of local anaesthetics with adrenaline into the hand and digits to create a bloodless operating field without the requirement for a tourniquet. Lalonde et al report on 3100 cases of elective use of adrenaline in the hand. No cases required phentolamine rescue for reversal of ischaemia.¹⁸ This finding is also corroborated by Tang et al who report outcomes in over 5000 WALANT cases; none developed digital necrosis. This proves the safety of using local anaesthetics with adrenaline in the hand at appropriate concentrations.¹⁹ However, the concentration of adrenaline administered by an AAI is hundred times greater than the safe concentration recommended in WALANT, and, therefore, carries a much greater risk of adverse effects.¹⁵

Our evidence-based algorithm for AAI injury management proposes initial treatment with warming and early toxicology and tertiary hand surgery unit consultation. Phentolamine is a first-line treatment, however, in circumstances where this is not immediately obtainable, lidocaine may be administered (figure 4). Lidocaine is a safe medication used commonly in hand surgery and is readily available in the emergency department unlike phentolamine, which can be challenging to acquire in hospital, particularly in units less familiar with WALANT surgery. In the case presented here, treatment with a digital block using lidocaine was effective in rapid restoration of digital perfusion. While, in this case, lidocaine was administered as a digital block, quicker reversal may be seen by injection of lidocaine at the site of injury. Furthermore, the privileged vascular supply of the thumb, which has three perfusing digital vessels compared with two in the other digits, may have helped avoid phentolamine rescue in this case.²⁰ We, therefore, recommend phentolamine as first-line treatment. When phentolamine is not immediately available within a department or there are anticipated delays in acquiring it, lidocaine administration may be a reasonable alternative. Phentolamine should ideally be available on standby for refractory cases where lidocaine administration and warming fail to reverse ischaemia.

Figure 4.

Proposed treatment algorithm for management of accidental AAI induced digital ischaemia. AAI, adrenaline auto-injectors.

Learning points.

• Accidental adrenaline auto-injector (AAI) injury-induced digital ischaemia can have detrimental effects with severe pain, digital necrosis and amputation described in severe cases.

• There is a need for an evidenced-based treatment algorithm for the management of AAI injuries.

• Our evidence-based algorithm proposes warming and first-line treatment with phentolamine for AAI injuries, but when this is not immediately available, lidocaine administration can be considered.

• This algorithm should aid the emergency department clinician and hand surgeon in managing this increasingly common and potentially catastrophic injury safely and with confidence