What is the optimal approach to infiltration and extravasation of nonchemotherapy medications?

Abby Tarpey; Shraddha Narechania; Mark Malesker

doi:10.3949/ccjm.90a.22029

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TABLE 1

Grading the severity of extravasation damage

Grade	Presentation	Treatment
1	Minimal swelling, pain at infusion site	Stop infusion Remove cannula and tapes Elevate
2	Pain at infusion site, mild swelling, no skin-blanching, minimal redness, normal capillary refill time	Stop infusion Remove cannula and tapes Elevate
3	Pain at infusion site, swelling, skin-blanching with or without redness at the infusion site, sluggish capillary refill time, normal or decreased perfusion, hard to flush cannula	Stop infusion Leave cannula until reviewed by a doctor Photograph injury if this will not delay treatment Provider to commence irrigation procedure within 1 hour of extravasation by irrigating affected area using saline or appropriate antidote Apply nonocclusive dressing as advised Elevate limb Consider plastic surgery team consult Nursing staff to continue to observe the site hourly for the first 24 hours to monitor for adverse effects Provider should review the site 1–2 hours after antidote to assess effectiveness, and reviewed again in 24 hours
4	Pain at infusion site, marked swelling, skin-blanching, coolness, reduced capillary refill time, decreased perfusion, with or without arterial occlusion, with or without blistering	Stop infusion Leave cannula until reviewed by clinician Photograph injury if this will not delay treatment Commence irrigation procedure within 1 hour of extravasation by irrigating affected area using saline or appropriate antidote Apply nonocclusive dressing as advised Elevate limb Refer to plastic surgery team Nursing staff to continue to observe the site hourly for the first 24 hours to monitor for adverse effects Review the site 1–2 hours after antidote to assess effectiveness, and review again in 24 hours

Based on information in references 5 and 6.

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TABLE 2

Current antidotes for intravenous extravasation

Antidote	Mechanism and use	Preparation	Administration
Sodium thiosulfate^5–7	Neutralizes reactive species and reduces formation of hydroxyl radicals that can cause tissue injury Used as first line for most vesicants	From 25% sodium thiosulfate solution: mix 1.6 mL with 8.4 mL sterile water for injection From 10% sodium thiosulfate solution: mix 4 mL with 6 mL sterile water for injection	Use 2 mL of the prepared solution for each 1 mg of drug extravasated
Hyaluronidase⁷	Hydrolyzes hyaluronic acid in connective tissue, possibly leading to dilution and diffusion of extravasated drug Used as first line for most vesicants	To obtain a 15-unit/mL concentration, mix 0.1 mL (of 150 units/mL) with 0.9 mL of 0.9% sodium chloride in 1-mL syringe Usually dosed as 15 to 25 units intradermally over 5 injections	Ideally administer within 1 hour of the event
Phentolamine^5,7	Alpha-adrenergic antagonist that promotes vasodilation and capillary blood flow Used as preferred agent for vasopressors	5 to 10 mg in 10 to 20 mL of 0.9% sodium chloride	Administer within 12 to 13 hours of the injury
Nitroglycerin topical^5,7	Increases nitric oxide, promoting vasodilation Used for vasopressors (alternative to phentolamine	2% ointment: A half-inch of ointment equals 7.5 mg of nitroglycerin 5-mg/day transdermal patch	1-inch strip applied to site of ischemia; can re-dose every 8 hours as necessary 1 patch daily
Terbutaline^5,7	Alpha-adrenergic agonist that promotes vasodilation and capillary blood flow Used for vasopressors (alternative to phentolamine)	1 mg in 10 mL of 0.9% sodium chloride	Inject locally across symptomatic sites

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TABLE 3

Antidotes for nonchemotherapy drug extravasation

Extravasated drug	Classification: vesicant or irritant	Immediate topical treatment	Antidote
Acyclovir^2,5-7	Irritant or vesicant; alkaline agent (pH 11)	Cooling	Hyaluronidase
Aminophylline^2,4	Vesicant; alkaline agent (pH 8–10)	Warming	Hyaluronidase
Amiodarone^1,6,8	Vesicant; acidic agent (pH 3.5–4.5)	Warming	Hyaluronidase
Amphotericin B⁴	Vesicant; acidic agent (pH 5–7)	Cooling	Hyaluronidase; for liposomal, consider flushout instead
Ampicillin⁴	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Calcium chloride 10%^2,4	Vesicant; hyperosmolar agent	Warming	Early-onset: hyaluronidase Delayed-onset: sodium thiosulfate
Dantrolene⁴	Vesicant; alkaline agent (pH 9.5–10.3)	Warming	Hyaluronidase
Dextrose 10%–50%⁴	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Dobutamine^2,4	Vesicant; vasopressor	Warming	First-line: phentolamine Second-line: terbutaline/topical nitroglycerin
Dopamine^2,4	Vesicant; vasopressor	Warming	First-line: phentolamine Second-line: terbutaline/topical nitroglycerin
Doxycycline⁴	Vesicant; acidic agent (pH 1.8–3.3)	Warming	Hyaluronidase
Epinephrine^2,4	Vesicant; vasopressor	Warming	First-line: phentolamine Second-line: terbutaline/topical nitroglycerin
Esmolol⁴	Vesicant; acidic agent (pH 4.5–6.5)	Warming (no literature support)	Hyaluronidase
Etomidate^2,4	Irritant (rarely vesicant); hyperosmolar agent	Warming (no literature support)	Hyaluronidase
Lorazepam⁴	Vesicant; hyperosmolar agent	Warming (no literature support)	Hyaluronidase
Mannitol 20%⁴	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Metronidazole⁴	Vesicant; acidic agent (pH 5.5)	Warming (no literature support)	Hyaluronidase
Methylene blue⁴	Vesicant; vasopressor	Warming (no literature support)	First-line: topical nitroglycerin Second-line: phentolamine or terbutaline
Nafcilllin⁴	Vesicant or irritant	Warming	Hyaluronidase
Nitroglycerin²	Vesicant; hyperosmolar agent	Warming or cooling	Hyaluronidase
Norepinephrine^2,4	Vesicant; vasopressor	Warming	First-line: phentolamine Second-line: terbutaline/topical nitroglycerin
Parenteral nutrition^2,4	Vesicant; hyperosmolar agent	Warming	Hyaluronidase, nitroglycerin
Pentobarbital⁴	Vesicant; alkaline agent (pH 9–10.5)	Warming	Hyaluronidase
Phenobarbital^2,4	Vesicant; hyperosmolar agent	Warming (no literature support)	Hyaluronidase
Phenylephrine^2,4	Vesicant; vasopressor	Warming	First-line: phentolamine Second-line: topical nitroglycerin
Phenytoin and fosphenytoin^2,4	Vesicant; alkaline agent (pH 10–12)	Warming	Hyaluronidase or nitroglycerin
Potassium chloride^2,4	Irritant; hyperosmolar agent	Warming	Hyaluronidase
Potassium phosphate⁶	Irritant; hyperosmolar agent	Cooling	Hyaluronidase
Sodium bicarbonate 8.4%^2,4	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Sodium chloride (> 3%)^2,4	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Sodium phosphate⁴	Vesicant; hyperosmolar agent	Warming	Hyaluronidase
Penicillin⁴	Vesicant	Warming (no literature support)	Hyaluronidase
Valproate⁴	Vesicant	Cooling	Hyaluronidase with washout
Vancomycin⁴	Irritant or vesicant; acidic agent	Warming (no literature support)	Hyaluronidase
Vasopressin⁴	Vesicant; vasopressor	Warming	First-line: topical nitroglycerin Second-line: phentolamine or terbutaline