What Is Perflutren and Why Is It Used?
Perflutren is a type of ultrasound contrast agent (UCA), marketed under brand names like Definity® and Optison™, that is used to enhance images during an echocardiogram. The agent consists of tiny, gas-filled microspheres that are injected into a vein. These microspheres reflect sound waves differently than blood, creating a clearer picture of the left ventricular chamber and improving the delineation of the endocardial border. This improved visualization is particularly helpful when a patient’s standard echocardiogram images are of suboptimal quality due to factors like obesity or lung disease. The use of UCAs allows clinicians to make more accurate diagnoses of heart conditions by providing a better view of the heart's function and structure.
Serious Risks and FDA Warnings
While perflutren offers significant diagnostic benefits, its use is associated with a boxed warning from the U.S. Food and Drug Administration (FDA) regarding serious cardiopulmonary reactions. These reactions, which can include fatalities, occur uncommonly but often within 30 minutes of administration. The risk is elevated for patients with unstable cardiopulmonary conditions. Healthcare facilities must have cardiopulmonary resuscitation equipment and trained personnel readily available whenever perflutren is administered due to these risks. Close patient monitoring is mandatory for at least 30 minutes following the injection to watch for any adverse reactions.
Contraindications and Safety Precautions
Not all patients are candidates for perflutren. Before receiving the contrast agent, all patients must be assessed for any conditions that would preclude its use. Key contraindications and safety considerations include:
- Known Hypersensitivity: Patients with a known or suspected allergy to perflutren, its components, or excipients like polyethylene glycol (PEG) should not receive the drug. Serious allergic reactions, including anaphylaxis, can occur even in patients with no prior exposure.
- Cardiac Shunts: Patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts are at risk for microvascular embolization, as the microspheres can bypass the lungs and enter arterial circulation.
- Ultrasound Settings: A high ultrasound mechanical index (MI) can cause the microspheres to rupture and has been reported to induce ventricular arrhythmias. The safety of perflutren at MI values greater than 0.8 has not been evaluated, and lower settings are often recommended.
- Albumin-Containing Products: Some formulations, like Optison, contain human albumin. While donor screening reduces the risk of viral transmission, it's a consideration for patients with hypersensitivity to albumin.
- Sickle Cell Disease: Patients with sickle cell disease have experienced pain episodes, including vaso-occlusive crises, after administration. Discontinuation is recommended if new or worsening pain occurs.
Comparison: Patient Safety with Perflutren
To better understand the risk profile, it is helpful to compare the general safety of perflutren in healthy individuals versus those with pre-existing cardiopulmonary conditions.
| Aspect | Generally Healthy Patients | Patients with Unstable Cardiopulmonary Conditions | Patient Monitoring and Precautions |
|---|---|---|---|
| Incidence of Serious Adverse Events | Low | Uncommonly high | Mandatory close monitoring for at least 30 minutes post-injection. Resuscitation equipment must be ready. |
| Common Adverse Reactions | Headache, dizziness, flushing, nausea, back pain, injection site pain. | Same common reactions, but with higher risk for serious cardiopulmonary events. | Thorough pre-screening for contraindications and risk factors is critical. |
| Risk of Anaphylaxis | Very rare, but possible. | Possible, potentially increased in patients with prior PEG hypersensitivity. | History of allergies, particularly to PEG, must be carefully reviewed. |
| Drug Interactions | Not extensively studied, but interactions with other medications are possible. | Potential for increased risk in patients on various medications. | Patient's full medication list must be reviewed before administration. |
Common and Serious Side Effects
Beyond the rare but severe cardiopulmonary and anaphylactic reactions, patients may experience more common side effects:
- Common Side Effects: Headache, flushing (warmth, redness), dizziness, nausea, chest pain, and pain or irritation at the injection site.
- Less Common Side Effects: Nausea, back pain, feeling of warmth, and redness of the face or neck.
- Signs of a Serious Reaction: Patients should immediately inform their healthcare provider if they experience severe dizziness, chest pain, wheezing, shortness of breath, or an irregular heartbeat.
Conclusion
So, is perflutren safe? For the vast majority of patients without significant cardiopulmonary instability or specific allergies, perflutren is a safe and highly effective diagnostic tool when administered by trained personnel under close observation. The FDA's boxed warning serves as a crucial reminder of the potential for rare but serious adverse events, particularly in high-risk populations. The key to ensuring safety lies in careful patient screening, adherence to contraindications, and vigilant monitoring during and after administration.
Clinicians can refer to the {Link: FDA website https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021064s017lbl.pdf} for more detailed prescribing information and risk assessments.
