UMEM Educational Pearls

Category: Pharmacology & Therapeutics

Title: A "Stick-y" Situation: Treatment of Epinephrine Autoinjector-Induced Digital Ischemia

Keywords: epinephrine, anaphylaxis, allergy, digital ischemia, phentolamine, nitroglycerin ointment, terbutaline (PubMed Search)

Posted: 10/12/2023 by Alicia Pycraft
Click here to contact Alicia Pycraft

Background: It is estimated that nearly 6% of U.S. adults and children report having a food allergy.1,2 Epinephrine autoinjectors are used to provide life-saving pre-hospital treatment for patients experiencing anaphylaxis in the community, but can have serious consequences if administered incorrectly. Accidental finger-stick injuries with epinephrine auto-injector can result in significant pain and ischemia due to vasoconstriction and decreased blood flow to the digit. Treatments for digital epinephrine injection include supportive care, topical vasodilators, and injectable vasodilators.3

Supportive care3,4:

  • Warm compresses are preferred to increase local blood flow and enhance removal of the drug. Cold compresses may result in worsening ischemia. 
  • Apply for 15 minutes every 6 hours
Topical nitroglycerin3-6:
  • Increases production of nitric oxide which relaxes smooth muscles and causes vasodilation
  • Literature shows variable symptomatic improvement for adults and neonates, but safe use as an adjunct to injectable vasodilators or as monotherapy.
  • Apply a 1-inch strip of nitroglycerin 2% ointment over the affected area and repeat every 8 hours until symptoms resolve
  • Patients should be monitored for hypotension after application, as topical nitroglycerin is systemically absorbed.
Phentolamine4, 7-9:
  • Alpha-1 adrenergic antagonist that competitively blocks alpha-adrenergic receptors to produce brief antagonism of circulating epinephrine and norepinephrine. Phentolamine also promotes vasodilation and increases capillary blood flow. 
  • Evidence for use after accidental injection of epinephrine autoinjector is mostly described in case reports, but one study showed that phentolamine was more effective at vasodilation than either nitroglycerin or sodium nitroprusside for treatment of digital norepinephrine injection. In another study of epinephrine-injected patients, subjects reported normal fingertip sensation in an average of 120 minutes after injection of phentolamine compared to 549 minutes after injection of saline. It took an average of 85 minutes for the epinephrine-injected digits to return to normal color after phentolamine injection compared to an average of 320 minutes after injection with saline.
  • Preparation/application: Dilute 5 mg of phentolamine in 10 mL of 0.9% sodium chloride. Inject small amounts subcutaneously into the affected area.
  • Beta-2 adrenergic agonist that causes vasodilation and attenuates the effect of alpha adrenoreceptor-mediated vasoconstriction.
  • Evidence shows that terbutaline has resulted in immediate and complete resolution of symptoms following accidental digital epinephrine injections if administered within 2 hours of the incident and it may be considered if phentolamine is not available.
  • Preparation/application: Dilute 1 mg of terbutaline with 1 mL of 0.9% sodium chloride and inject subcutaneously into the affected area.
  • May cause elevations in heart rate and blood pressure, as well as ECG changes. Terbutaline should be used cautiously in patients with cardiovascular disease.
Bottom line: Most cases of epinephrine autoinjector-induced digital ischemia can be conservatively managed with warm compresses and topical nitroglycerin, but phentolamine should be considered for patients with refractory pain or tissue ischemia. Terbutaline should be considered in the event of phentolamine shortage.


  1. Zablotsky B, Black LI, Akinbami LJ. Diagnosed allergic conditions in children aged 0–17 years: United States, 2021. NCHS Data Brief, no 459. Hyattsville, MD: National Center for Health Statistics. 2023.
  2. Ng AE, Boersma P. Diagnosed allergic conditions in adults: United States, 2021. NCHS Data Brief, no 460. Hyattsville, MD: National Center for Health Statistics. 2023.
  3. Stefanos S, Kiser T, MacLaren R, Mueller S, Reynolds P et al. Management of noncytotoxic extravasation injuries: update on medications, treatment strategies, and peripheral administration of vasopressors and hypertonic saline. Pharmacotherapy. 2023; 43:321-337.
  4. UMMC Adult Extravasation and Infiltration Guidelines – Updated October 2020.
  5. Plum M and Moukhachen O. P and T. Alternative pharmacological management of vasopressor extravasation in the absence of phentolamine. 2017; 42(9). 581-585, 592.
  6. NITRO-BID (nitroglycerin ointment 2%) [prescribing information]. Melville, NY: Savage Laboratories; Aug 2021.
  7. Phentolamine mesylate [prescribing information]. West-Ward Pharmaceuticals: Eatontown, NJ; Dec 2018.
  8. Coffmen J and Cohen R. Intra-arterial vasodilator agents to reverse human finger vasoconstriction. Clin Pharm Therap. 1987; 41(5):574-579.
  9. Nodwell T, Lalonde D. How long does it take phentolamine to reverse adrenaline-induced vasoconstriction in the finger and hand? A prospective, randomized, blinded study: the Dalhousie project experimental phase. Can J Plast Surg. 2003; 11(4):187-90.
  10. Terbutaline sulfate injection [prescribing information]. Hikma Pharmaceuticals Inc: Berkley Heights, NJ; May 2022.