Fluorescein is a fluorescent dye primarily utilized in ophthalmic procedures, like fluorescein angiography, to visualize blood vessels in the retina and iris. It is also used topically to detect corneal abrasions. While it is generally considered safe, a range of adverse events can occur, from mild, transient effects to severe, life-threatening complications. The type and severity of the hazard largely depend on the route of administration and the patient's individual risk factors.
Common Adverse Reactions
Following the intravenous injection of fluorescein, patients often experience several temporary side effects. The most frequently reported are gastrointestinal issues and aesthetic changes.
- Nausea and vomiting: Occurring in 1% to 10% of patients, this is the most common adverse reaction, typically subsiding within 10 minutes. Pre-treatment with anti-nausea medication can help for those with a history of this side effect.
- Metallic taste: A peculiar or strong taste in the mouth is a common experience after intravenous administration.
- Skin and urine discoloration: The dye causes a temporary yellowish discoloration of the skin, which usually fades within 6 to 12 hours. The urine will appear bright yellow for 24 to 36 hours as the dye is eliminated by the kidneys.
- Other symptoms: Patients might also experience headache, abdominal pain, or diarrhea.
Severe and Rare Systemic Hazards
Though rare, severe systemic reactions to fluorescein are well-documented and require immediate medical attention. These are most often associated with intravenous injection.
- Anaphylaxis: The most serious hazard is an unpredictable, severe allergic reaction known as anaphylaxis. Symptoms can include hives, itching, swelling of the face, lips, or tongue (angioedema), and severe difficulty breathing. In very rare cases, anaphylactic shock has led to cardiac arrest and death.
- Cardiopulmonary reactions: These can include severe hypotension (low blood pressure), chest pain, irregular or fast heartbeat, pulmonary edema, and cardiac arrest.
- Neurological events: Rare neurological hazards include seizures (convulsions), syncope (fainting), and confusion.
- Exacerbated reactions: Patients with a history of allergies, asthma, or previous adverse reactions are at a higher risk of experiencing a severe reaction.
The Danger of Extravasation
Extravasation occurs when the fluorescein solution leaks from the intended intravenous injection site into the surrounding soft tissue. This is a particularly painful and potentially damaging local complication.
- Intense pain: Leakage of the dye causes intense, burning pain at the injection site that can radiate up the arm.
- Tissue damage: Because of its high pH, fluorescein can cause significant local tissue damage. Complications reported from extravasation include skin sloughing, tissue necrosis, superficial phlebitis, and subcutaneous granulomas.
- Nerve injury: Toxic neuritis, or inflammation of a nerve, along the median nerve in the antecubital area has also been reported following extravasation.
- Prevention: The risk of extravasation is mitigated by using careful injection techniques and monitoring the injection site closely.
Comparison of Fluorescein Administration Routes
While the hazards of fluorescein are most pronounced with intravenous use, adverse reactions can occur with other methods as well. The following table summarizes the typical risk profile for the three main routes.
| Route | Common Side Effects | Risk of Anaphylaxis | Local Complications |
|---|---|---|---|
| Intravenous (IV) | Nausea, vomiting, metallic taste, skin/urine discoloration | Low but documented risk of severe, potentially fatal anaphylaxis | Extravasation causing severe pain, tissue damage, and necrosis |
| Oral | Similar systemic reactions, including nausea and vomiting | Possible but likely lower than IV | No specific local risk at injection site; bitter taste |
| Topical (Eye Drops) | Ocular irritation and stinging | Extremely rare but cases of systemic anaphylaxis have been reported | Mild conjunctival chemosis and irritation |
Precautions and Contraindications
To ensure patient safety, healthcare providers must be aware of certain precautions and contraindications associated with fluorescein use.
- History of hypersensitivity: Any known history of allergic reactions to fluorescein, no matter how mild, is a significant risk factor. A history of severe anaphylaxis is an absolute contraindication to re-administration.
- Asthma and allergies: Patients with a history of allergies, especially severe asthma, are at a higher risk for adverse reactions. Pre-treatment with antihistamines or corticosteroids may be considered for high-risk individuals.
- Pregnancy and breastfeeding: Fluorescein is a Category C drug, and due to a lack of controlled studies, it is typically avoided in pregnant women, especially during the first trimester. Fluorescein is excreted in breast milk, so nursing mothers may be advised to suspend breastfeeding for a few days after administration.
- Cardiovascular and renal disease: While not an absolute contraindication, the healthcare team should be aware of a patient's history of cardiovascular or renal issues to manage potential allergic reactions effectively.
- Emergency preparedness: Facilities administering intravenous fluorescein should have emergency equipment and trained staff ready to manage anaphylaxis or other severe reactions.
Drug Interactions to Monitor
While fluorescein is not known for frequent drug interactions, there are a few considerations to note.
- Interference with lab tests: The dye can interfere with the results of certain blood and urine tests for up to three to four days after administration.
- Organic anion transporters: Fluorescein is eliminated via organic anion transporters, and other drugs that inhibit or compete for this transport, such as probenecid, may increase its systemic half-life.
- Beta-blockers and ACE inhibitors: Patients on beta-blockers may have a blunted response to epinephrine, complicating the management of anaphylaxis. Patients on ACE inhibitors also face an increased risk of adverse reactions.
Conclusion
Fluorescein is an invaluable diagnostic agent, particularly in ophthalmology. However, it is not without hazards. While most side effects are mild and transient, such as nausea and discoloration, there are also rare but severe risks, including anaphylaxis and tissue-damaging extravasation. The route of administration, whether intravenous, oral, or topical, influences the risk profile, with IV injection carrying the highest potential for systemic complications. Careful patient screening, awareness of contraindications and potential drug interactions, and appropriate emergency preparedness are essential for mitigating these risks and ensuring safe administration.
For more detailed information on fluorescein, particularly its pharmacological properties and administration guidelines, refer to reputable resources like the National Institutes of Health (NIH) or specific product information sheets.
Final Thoughts on Safety
Clinicians should always weigh the diagnostic benefits against the potential hazards, especially in high-risk patients. For those with a history of prior reactions or significant allergies, alternative diagnostic methods, or appropriate premedication protocols, should be considered. Open communication with patients about potential side effects, like temporary discoloration and nausea, can also help manage expectations and reduce anxiety during a procedure.
