What medication should be administered for norepinephrine (Levophed) intravenous infiltration?

Treatment of Norepinephrine (Levophed) IV Infiltration

Phentolamine is the medication of choice for norepinephrine extravasation, administered as 5-10 mg diluted in 10-15 mL of saline, infiltrated intradermally at the site of extravasation as soon as possible to prevent tissue necrosis. 1

Immediate Management Protocol

Recognition and Initial Response

• Stop the norepinephrine infusion immediately but maintain IV access at the site 2
• Assess the extent of extravasation by examining for blanching, induration, erythema, or hematoma formation 3
• Document the estimated volume of extravasation and time of occurrence 3

Phentolamine Administration (First-Line Antidote)

Adult Dosing:

• Infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of 0.9% sodium chloride solution intradermally at the extravasation site 1, 4
• Inject the solution in a circumferential pattern around the affected area, using multiple small injections rather than a single bolus 1
• Administer as soon as possible after recognition—ideally within 10-12 hours of extravasation for maximum effectiveness 5, 6

Pediatric Dosing:

• Use 0.1-0.2 mg/kg of phentolamine (maximum 10 mg) diluted in 10 mL of 0.9% sodium chloride 1
• Follow the same intradermal infiltration technique as adults 1

Mechanism of Phentolamine Action

• Phentolamine is an alpha-adrenergic antagonist that reverses the intense vasoconstriction caused by norepinephrine extravasation 5, 6
• It prevents tissue necrosis by restoring blood flow to the affected area before irreversible ischemic damage occurs 5, 4
• Animal studies demonstrate that phentolamine is highly effective when administered within 10 minutes of extravasation, with clinical efficacy extending up to 12 hours 6

Adjunctive Supportive Measures

Topical Nitroglycerin Application

• Apply nitroglycerin paste topically to the affected area after phentolamine administration 4
• This provides additional vasodilation and may enhance tissue perfusion 4
• The combination of phentolamine injection plus topical nitroglycerin has been shown to prevent local ischemic injury in clinical practice 4

Monitoring and Follow-Up

• Evaluate the extravasation site every 2-4 hours for the first 24 hours, assessing for progression of tissue injury 3
• Watch for signs of worsening ischemia: increasing blanching, darkening of tissue, or development of blisters 3
• Most extravasations treated promptly with phentolamine result in no or minimal tissue injury 7, 4

Evidence Supporting Phentolamine Use

Clinical Efficacy Data

• A prospective study of 635 patients receiving peripheral norepinephrine found that extravasation occurred in 35 patients (75.8 events per 1,000 catheter-days), with no patient requiring surgical intervention when treated with the standard protocol 7
• In a medical ICU study of 734 patients, extravasation occurred in only 19 patients (2%), and all cases resolved without tissue injury following treatment with phentolamine and nitroglycerin 4
• Animal studies demonstrate that phentolamine prevents tissue necrosis from norepinephrine extravasation when administered within 10 minutes 6

Comparison to Other Agents

• Phentolamine is superior to labetalol for preventing tissue necrosis from catecholamine extravasation 5
• While terbutaline has been mentioned in some extravasation protocols, phentolamine remains the evidence-based first-line antidote specifically for norepinephrine 3

Critical Pitfalls to Avoid

Timing Errors

• Do not delay phentolamine administration waiting for surgical consultation—tissue necrosis can develop rapidly, and early intervention is critical 1, 5
• The window for maximum effectiveness is within the first 10-12 hours, though benefit may extend beyond this timeframe 5, 6

Technical Errors

• Do not inject phentolamine as a single bolus—use multiple small intradermal injections in a circumferential pattern to ensure adequate distribution 1
• Do not remove the IV catheter before administering phentolamine, as the catheter site helps identify the exact location of extravasation 2

Monitoring Failures

• Do not assume a single phentolamine dose is sufficient—reassess the site and consider repeat administration if ischemia persists or worsens 3
• Do not discharge patients immediately after treatment—observe for at least 24 hours to ensure no progression of tissue injury 2

Prevention Strategies

Preferred Administration Routes

• Central venous access is strongly preferred for norepinephrine administration to minimize extravasation risk 1, 8
• If peripheral administration is necessary, use large-bore catheters in proximal veins (antecubital fossa preferred over hand or wrist) 7, 4
• Implement strict monitoring protocols with hourly IV site checks when using peripheral access 7, 4

Early Recognition Systems

• Train nursing staff to recognize early signs of extravasation: pain at the IV site, blanching, swelling, or resistance to infusion 7, 4
• Consider using infusion pumps with pressure alarms to detect early infiltration 7
• Transition to central access as soon as practical if prolonged vasopressor therapy is anticipated 1, 8