First line:

1. Apply 4 mm/kg of 2% nitroglycerine ointment to the affected area

First line:

1. Inject 0.5 mg of concentrated terbutaline (1 mg/10 mL) subcutaneously into the area of extravasation.
2. Apply enough 2% nitroglycerine ointment to cover the affected area.

First line:

1. Inject 0.5 mg of concentrated terbutaline (1 mg/10 mL) subcutaneously into the area of extravasation.
2. Apply enough 2% nitroglycerine ointment to cover the affected area.

If no improvement or residual symptoms:

• Reapply nitroglycerin ointment 8 hours after the first dose.

If improvement is seen, but residual symptoms persist after the second application: 

• Apply the same nitroglycerin dose q8h until symptoms fully resolve.

If inadequate or no improvement seen:

• Repeat terbutaline dose 15 mins later

If refractory to nitroglycerin:

• Administer 0.1 mg of diluted terbutaline (1 mg/10 mL) subcutaneously to the site of extravasation.

If improvement is seen, but residual symptoms remain:

• Reapply topical nitroglycerin 8 hours later. This may be reapplied q8h until symptoms resolve.

Once treatment success is achieved:

• Monitor for full symptom resolution, symptom worsening, or hemodynamic instability.
• The affected site should be routinely checked for erythema, blanching, necrosis, swelling, drainage, pain, or changes in temperature.

Accidental digital epinephrine injection: To treat or not to treat?

Design

Case Presentation

A 68-year-old male presented to the emergency department (ED) with a cold and pale thumb after accidentally injecting himself with his wife’s epinephrine autoinjector pen. The accidental injection occurred 20 minutes prior to arrival, and he reported injecting most of the epinephrine into the pulp of his thumb. Upon presentation, his thumb was cold, numb, and pale, and there was no capillary refill distally; an area extending proximally past the interphalangeal joint was insensible.

The thumb was soaked in warm water for 30 minutes with no change. Nitroglycerin paste (strength unspecified) was then applied. Sensation slowly began to return to the digit 45 minutes later. Within 2 hours, capillary refill had improved, but sensation remained diminished compared with the other digits. After 4 to 5 hours, the capillary refill had substantially improved; however, the sensation still had not fully returned to normal. There was no follow-up information on if the sensation returned to normal after discharge.

Study Author Conclusions

Accidental digital injection of epinephrine is an increasingly common occurrence and can be associated with profound ischemia of the affected digit. Choosing an appropriate management plan can be challenging because it is often difficult to assess the amount of epinephrine that has been injected into the digit. Although there is currently no clear treatment protocol for accidental digital epinephrine injection, conservative measures (e.g., warming, topical nitroglycerin) can safely be tried initially. If the digital ischemia does not respond, injection with phentolamine is advisable.

Two Cases of Accidental Epinephrine Injection into a Finger

Design

Case presentation

A 41-year-old female presented with an accidental epinephrine autoinjector (EpiPen) injection to her finger while attempting to administer the dose to her son; she injected a likely full 0.3-mg dose into her own thumb rather than her son’s thigh as intended. She reported significant pain, progressive pallor, and coldness extending proximally from the end of her thumb to her forearm over the next 30 minutes.

Two rounds of nitroglycerin paste were applied to the affected area over an hour at an emergency department. After no improvement, hot packs were applied and provided some benefit (approximately 2.5 hours after the accidental injection). The hot packs were continued for 1 hour before the patient was discharged home with instructions to continue warm water soaks for the rest of the evening. Full circulation returned the next morning.

Study Author Conclusions

Accidental epinephrine infection can be initially managed with warm soaks at home, referral to the emergency department for refractory cases, and additional therapy with topical nitroglycerin or phentolamine injection if tissue ischemia seems imminent.

Use of Subcutaneous Terbutaline to Reverse Peripheral Ischemia

Design

Case 1

A 65-year-old male with a history of congestive heart failure and renal failure was admitted to the intensive care unit for myocardial infarction and started on a dopamine and dobutamine infusion for hypotension. The dopamine infusion was promptly discontinued when the dorsum of the hand and wrist was noted to be pale and swollen. After discovering that there was no phentolamine available, the decision was made to try subcutaneous terbutaline after pharmacy and poison control consultation.

A solution containing 1 mg terbutaline in 10 mL normal saline was prepared, and 10 mL was infiltrated into the subcutaneous tissue of the blanched areas 1 hour after noticing the extravasation. Almost immediately, the infiltrated areas became hyperemic with a return of normal skin color. There were no untoward effects from the administration of terbutaline, and the hand was normal at the time of discharge from the hospital 12 days later.

Case 2

A 13-year-old girl presented to the emergency department (ED) approximately 20 minutes after accidentally discharging an epinephrine autoinjector into the pad of her right thumb. Her general physical examination was unremarkable; however, the patient's right thumb was cool, pale, and demonstrated decreased capillary refill to the nail bed. The finger had a diminished range of motion secondary to pain. Two-point discrimination and soft touch sensation were intact. There was severe local pain and pallor extending to the proximal wrist.

Since the hospital had no available phentolamine, the poison center suggested an injection of local subcutaneous terbutaline. Approximately 1.5 hours after the original injury, 3 mL of a solution of terbutaline (1 mg in 10 mL normal saline) was injected subcutaneously into the original puncture site. The thumb pad became progressively pink during injection, and within 2 to 3 minutes, an area of hyperemia developed around the injection site.

About 10 minutes later, nitroglycerin ointment was also applied over the entire digit. Significant symptomatic improvement and return of normal skin color had already occurred. Within 30 minutes the thumb had completely returned to normal color and warmth, and the patient was discharged with instructions to follow up with a hand surgeon. Telephone follow-up 1 month later found no adverse long-term sequelae.

Case 3

A 39-year-old woman presented to the ED after accidentally discharging an epinephrine autoinjector into the pad of her right thumb. Her general physical exam was unremarkable; however, the patient's right thumb was cool, pale, and demonstrated decreased capillary refill to the nail bed. There was also an area of blue discoloration on the thumb pad measuring approximately 0.25 cm in diameter. The patient complained of severe local pain at the injection site but maintained full range of motion.

Since there was no phentolamine available, this case was initially treated with topical nitroglycerin and a warm compress to the affected area. Two hours post-injection, there was no apparent resolution of symptoms. Subcutaneous terbutaline 0.5 mL (1 mg in 1 mL of normal saline) was administered into the original puncture site. Immediately after terbutaline administration, the blanching resolved, and there was return of the normal pink color of skin.

Second doses of terbutaline and nitroglycerin ointment were given, and the patient was discharged after one hour of observation. At the time of discharge, the thumb had normal color and warmth, but remained tender and had slightly decreased capillary refill (less than 3 seconds).

Case 4

A 31-year-old female presented to the ED approximately 6 hours after accidentally discharging an epinephrine autoinjector into the pad of her right thumb. Her right thumb was cool, pale, and demonstrated decreased capillary refill to the nail bed. There was a visible puncture site with a small area of surrounding ecchymosis on the volar aspect of the thumb, approximately 1 cm proximal to the tip.

A 1:1 dilution of terbutaline (0.5 mg/mL) was prepared in normal saline, and 1 mL was injected subcutaneously into the original puncture site. Within a few minutes, the patient reported minimal relief of pain and a slight improvement in sensation. A repeat dose of terbutaline was given 15 minutes after the initial dose. After 1 hour of observation, there were no signs of ischemic progress. A hand surgeon was contacted, and this patient was able to receive an injection of phentolamine via digital block. The patient was discharged 1 hour later with full recovery of sensation.

Study Author Conclusions

The current treatment of choice for peripheral ischemic events secondary to the extravasation or accidental injection of alpha-adrenergic agents is local infiltration with phentolamine. Alternative therapies when phentolamine is unavailable include warm water immersion, amyl nitrite inhalations, metacarpal nerve block, intravenous chlorpromazine, intravenous nitroprusside, and use of topical nitroglycerin paste.

This case series suggests that terbutaline may also be an effective alternative to phentolamine for vasopressor extravasation. A 1:10 dilution was recommended in the first case to provide the maximum recommended dose of terbutaline with enough diluent to cover the affected area with infiltration of the antidote adequately. However, more localized ischemia in distal extremities was treated with a smaller volume of 1:1 terbutaline.

Topical Nitroglycerin for Management of Peripheral Extravasation of Vasopressors: A Case Report

Design

Case presentation

A 72-year-old male presented to the hospital with fever, chills, cough, and chest pain. His total leukocytes were 37,100/mm^3, and chest radiography showed consolidation in the right lung. He was transferred to the intensive care unit (ICU) with a diagnosis of pneumonia with septic shock.

In the ICU, he was started on norepinephrine 0.1 mcg/kg/min via a peripherally placed 18G intravenous (IV) cannula, which was placed on the dorsum of the left hand. His blood pressure started to stabilize, and he started to be tapered off the vasopressor after about 2 hours of therapy. The next morning (about 12 hours after norepinephrine infusion), swelling over the dorsum of the left hand with purplish discoloration was noted.

Due to the suspected norepinephrine extravasation, topical nitroglycerin 2% was applied to the affected area and repeated every 4 hours. The hand was kept elevated, and heat was applied. Neither phentolamine nor terbutaline was available. With continued elevation, heat, and topical nitroglycerin, swelling and discoloration gradually improved without further damage to the surrounding tissues. The swelling subsided within 48 hours of topical nitroglycerin treatment, and the skin texture was near normal.

Study Author Conclusions

Phentolamine mesylate is the only pharmacological treatment for vasopressor extravasation approved by the Food and Drug Administration. However, phentolamine is not readily available and has become relatively obsolete. While other treatment options come from case reports, no randomized controlled trials exist about the management of extravasation injuries.

Topical nitroglycerin 2% along with phentolamine has been shown to initiate reperfusion in case reports of patients with norepinephrine extravasation. In this patient, topical nitroglycerin helped manage the extravasation along with nonpharmacologic measures (i.e., elevation, heat).