Extravasation occurs when an intravenously administered medication leaks from the vein into the surrounding tissue. When this happens with vasopressor drugs like norepinephrine (Levophed) and dopamine, the consequences can be severe due to their potent vasoconstrictive properties. These agents constrict blood vessels to increase blood pressure, and when they leak into the tissue, they cause localized ischemia (restricted blood supply) that can lead to tissue damage, necrosis (death), and skin sloughing. Understanding the proper antidote and management is critical for preventing permanent harm.
The Urgency of Vasopressor Extravasation
Norepinephrine and dopamine are catecholamine vasopressors used in critical care settings to treat life-threatening hypotension and shock. While highly effective, their potent vasoconstriction makes extravasation a medical emergency. Once the drug infiltrates the subcutaneous tissue, it triggers intense local vasoconstriction, causing the affected area to become pale, cold, and painful. If not treated promptly, the sustained lack of blood flow can cause irreversible tissue injury and necrosis.
Immediate Management Steps
Early recognition and intervention are the most important factors for a positive outcome. The moment extravasation is suspected, a standardized protocol should be followed immediately:
- Stop the Infusion: The first and most critical step is to immediately stop the infusion to prevent further leakage of the vesicant drug into the tissue.
- Do Not Remove the Catheter: Leave the intravenous catheter or access device in place temporarily.
- Aspirate the Drug: Using a small syringe, attempt to aspirate any remaining drug and blood from the catheter to remove as much of the extravasated fluid as possible.
- Administer Antidote: Following aspiration, administer the specific antidote through the remaining IV catheter or via multiple subcutaneous injections around the extravasation site.
- Elevate the Limb: Raise the affected limb above the level of the heart to help reduce swelling and decrease hydrostatic pressure, which promotes reabsorption of the fluid.
- Apply Warm Compresses: Apply dry warm compresses to the area. This is a crucial distinction, as cold compresses would worsen the vasoconstriction caused by these vasopressors. The heat promotes vasodilation, increasing local blood flow and helping disperse the medication.
Phentolamine: The Gold Standard Antidote
Phentolamine mesylate is the only FDA-approved pharmacological antidote for vasopressor extravasation, including that caused by norepinephrine and dopamine.
Mechanism of Action
Phentolamine is a non-selective, reversible alpha-adrenergic blocker. Its action directly opposes the vasoconstrictive effects of norepinephrine and dopamine, which are potent alpha-adrenergic agonists. By blocking the alpha-adrenergic receptors in the affected tissue, phentolamine causes local vasodilation and improves blood flow to the ischemic area, preventing or reducing tissue damage. Clinical signs of success often include the immediate return of a pink color to the previously blanched area and improved capillary refill.
Administration
For adults, the typical dose is 5 to 10 mg of phentolamine, diluted in 10 mL of normal saline. This solution is infiltrated into the extravasation site using a fine hypodermic needle via multiple small, subcutaneous injections. This should be done as soon as possible after extravasation is noted, and is most effective when administered within 12 hours. The phentolamine can be injected liberally throughout the blanched, ischemic area.
Alternatives to Phentolamine
Due to historical and recent shortages of phentolamine, alternative pharmacological options have emerged. While not universally considered standard-of-care, these alternatives can be life-saving when phentolamine is unavailable.
- Terbutaline: A selective $eta_2$-agonist, terbutaline stimulates vasodilation, indirectly counteracting the vasoconstriction caused by vasopressors. Some case reports suggest terbutaline injections lead to rapid symptom resolution for dopamine and dobutamine extravasation. A typical approach involves injecting diluted terbutaline (e.g., 1 mg in 10 mL saline) subcutaneously into the affected area.
- Topical Nitroglycerin Ointment: A 2% topical nitroglycerin ointment can be applied to the extravasation site. It releases nitric oxide, which causes local vasodilation in smooth muscles and can improve perfusion. While effective, case studies indicate it may take longer to resolve symptoms compared to phentolamine or terbutaline.
What Is Not Used for Vasopressor Extravasation
It is equally important to know what not to use in these situations, as certain antidotes are specific to other types of extravasation injuries.
- Hyaluronidase: This enzyme works by breaking down the hyaluronic acid in the connective tissue, which allows extravasated fluids to disperse more easily. While effective for substances like hyperosmolar solutions and certain chemotherapeutic agents, hyaluronidase is not recommended for vasopressor extravasation. Its use in this context is controversial, and some studies suggest it is ineffective for this specific type of injury.
- Cold Compresses: As mentioned, cold causes further vasoconstriction, which would exacerbate the effects of norepinephrine and dopamine extravasation. This is the opposite of the desired effect, which is vasodilation to restore blood flow.
Comparison of Pharmacological Antidotes
| Antidote | Mechanism of Action | Timing | Effectiveness | Comments |
|---|---|---|---|---|
| Phentolamine | Non-selective alpha-adrenergic blocker; causes direct vasodilation by blocking vasoconstriction. | Within 12 hours of extravasation. | High; FDA-approved and gold standard. | Administered via subcutaneous injection. May be subject to supply shortages. |
| Terbutaline | Selective $eta_2$-agonist; causes vasodilation. | Most effective if administered early (within 2 hours). | Variable; effective in many cases, especially when phentolamine is unavailable. | Administered via subcutaneous injection. Not first-line for all vasopressors due to limited data. |
| Topical Nitroglycerin | Releases nitric oxide, causing smooth muscle relaxation and local vasodilation. | Applied topically to affected area every 8 hours until symptoms resolve. | Slower onset of action compared to injection. Variable efficacy. | Less invasive. Can be used in neonates or as an adjunct. |
Post-Extravasation Monitoring and Follow-Up
After the initial emergency treatment, the patient requires close monitoring for 24 to 72 hours. Regular assessment of the site for changes in color, temperature, swelling, and sensation is necessary. In severe cases or if symptoms persist, a surgical consultation for possible debridement or other interventions may be required to address necrotic tissue. Documentation of the event is also critical, including the time, affected area, drug, estimated volume, and all management steps taken.
Conclusion
While prompt action following the immediate cessation of infusion is paramount, the definitive pharmacological treatment for extravasation of norepinephrine and dopamine is the local infiltration of phentolamine. This alpha-adrenergic blocker reverses the intense vasoconstriction and restores blood flow to the affected tissue. In situations where phentolamine is unavailable, alternative vasodilators such as terbutaline and topical nitroglycerin can be used, although they may have different mechanisms and efficacy. Combining immediate non-pharmacological interventions, such as elevating the limb and applying warm compresses, with the appropriate antidote is the cornerstone of managing this serious medical event and minimizing patient harm.
Alternative Pharmacological Management of Vasopressor Extravasation in the Absence of Phentolamine
