Antidote for Norepinephrine Infiltration
Phentolamine 5-10 mg diluted in 10-15 mL of saline should be infiltrated intradermally into the extravasation site as soon as possible, ideally within 12 hours, to prevent tissue necrosis. 1
Immediate Management Protocol
Phentolamine Administration
- Inject 5-10 mg of phentolamine diluted in 10-15 mL of saline solution directly into the area of extravasation within 12 hours of occurrence 2, 1
- For pediatric patients, use 0.1-0.2 mg/kg up to a maximum of 10 mg diluted in 10 mL of 0.9% sodium chloride 2
- The injection should be intradermal at the site to counteract dermal vasoconstriction 2
- Administer as soon as extravasation is recognized—do not delay treatment 2, 1
Mechanism of Action
- Phentolamine is an alpha-adrenergic blocking agent that reverses the intense vasoconstriction caused by norepinephrine extravasation 1
- By blocking alpha-1 receptors, it restores blood flow to the affected tissue and prevents ischemic necrosis 2
Prevention Strategies
Prophylactic Phentolamine Use
- For high-risk situations, 10 mg of phentolamine can be added to each liter of norepinephrine solution as a preventive measure 1
- This prophylactic addition does not affect the pressor effect of norepinephrine 1
Optimal Administration Practices
- Central venous access is strongly preferred for norepinephrine administration to minimize extravasation risk 2, 3
- If peripheral administration is necessary, use 16-20 gauge catheters in the mid-to-upper arm (avoid hand sites) 2, 4
- Limit peripheral infusion to low doses (<0.25 mcg/kg/min) and short duration (<24 hours) 2, 5
- Monitor IV sites every 2 hours during infusion for signs of infiltration 5
Clinical Outcomes and Safety Data
Evidence for Phentolamine Efficacy
- The FDA explicitly recommends phentolamine as the treatment for norepinephrine extravasation to prevent tissue death and sloughing 1
- When administered promptly, phentolamine effectively prevents the dermal necrosis that would otherwise occur from norepinephrine-induced vasoconstriction 2, 1
Peripheral Norepinephrine Safety Profile
- Recent observational studies show low complication rates (3-5.45%) with peripheral norepinephrine administration when protocols are followed 6, 5
- In a study of 98 patients receiving peripheral norepinephrine, only 3 developed complications (all minor: 2 local extravasations, 1 thrombophlebitis), and none required medical or surgical intervention 6
- No significant tissue injury occurred in 124 patients across multiple studies when appropriate monitoring was maintained 4
Critical Pitfalls to Avoid
- Do not delay phentolamine administration—the 12-hour window is critical, but earlier treatment is better 1
- Do not use inadequate dilution—always dilute phentolamine in 10-15 mL of saline to ensure proper tissue distribution 2, 1
- Avoid hand sites for peripheral norepinephrine infusion—complications are more common in distal extremities 6
- Do not continue infusion through a suspected infiltrated line—stop immediately and assess 5
- Ensure adequate volume resuscitation before starting norepinephrine to optimize cardiac output and minimize the need for high doses that increase extravasation risk 7, 3