Management of Norepinephrine (Levophed) Infiltration
If norepinephrine extravasation occurs, immediately infiltrate the affected area with 5-10 mg of phentolamine diluted in 10-15 mL of normal saline as soon as possible to prevent tissue necrosis and sloughing 1.
Immediate Actions
When you recognize norepinephrine infiltration, take these steps in rapid sequence:
1. Stop the Infusion and Assess
- Immediately discontinue the norepinephrine infusion
- Keep the IV access patent (do not remove the catheter yet)
- Assess the extent of extravasation by examining for blanching, swelling, or skin changes along the vein course
2. Administer Phentolamine (The Antidote)
This is the definitive treatment and should be given without delay:
- Dose: 5-10 mg of phentolamine 1, 2
- Dilution: Mix in 10-15 mL of 0.9% sodium chloride 1, 2
- Administration: Inject intradermally/subcutaneously at multiple sites throughout the extravasation area in small aliquots 2, 3
- Pediatric dose: 0.1-0.2 mg/kg (maximum 10 mg) 2
The mechanism is straightforward: phentolamine is an alpha-adrenergic antagonist that directly counteracts norepinephrine's vasoconstrictive effects on the dermal vasculature 2. Clinical response is often dramatic—you may see the blanched area turn pink within minutes to hours 3.
3. Supportive Measures
After phentolamine administration:
- Apply warm compresses to the affected area to promote vasodilation 4
- Elevate the extremity if feasible
- Document thoroughly: time of extravasation recognition, estimated volume extravasated, interventions performed, and serial assessments of the site
Critical Prevention Strategies
The FDA label and AHA guidelines emphasize prevention 5, 1:
Preferred IV Access Sites
- First choice: Large antecubital veins 5
- Acceptable alternative: Femoral vein 5
- Avoid: Lower extremity veins, especially in elderly patients or those with peripheral vascular disease (atherosclerosis, diabetes, Buerger's disease) 5
- Never use: Ankle veins—gangrene has been reported 5
Monitoring Requirements
- Check the infusion site frequently for free flow 5
- Use a central line whenever possible 1, 5
- If using peripheral access, employ strict protocols with dilute concentrations 6
- Avoid catheter tie-in techniques that promote stasis 5
Important Caveats
Blanching without obvious extravasation can occur due to vasa vasorum constriction, which increases vein wall permeability and allows drug leakage 5. This may progress to superficial slough, particularly in leg veins of elderly or vascular disease patients. If blanching occurs, strongly consider changing the infusion site even without frank extravasation 5.
Hyaluronidase is NOT indicated for norepinephrine extravasation. While you mentioned it in your question, the evidence-based treatment is phentolamine, which directly antagonizes alpha-adrenergic receptors. Hyaluronidase is used for other types of extravasation injuries but has no role here.
Expected Outcomes
Recent evidence is reassuring when proper protocols are followed:
- Most extravasations cause minimal or no tissue injury with prompt phentolamine treatment 7
- In a large prospective study of 635 patients receiving peripheral norepinephrine, extravasation occurred in 35 patients (5.5%), but no patient required surgical intervention 7
- Case reports document complete healing within 7-10 days when phentolamine is administered promptly 3
- Tissue necrosis requiring surgical debridement is rare and typically occurs when treatment is delayed or phentolamine is unavailable 4
The key is early recognition and immediate phentolamine administration—delays increase the risk of permanent tissue damage.