What is the use of Perflutren (Definity, generic name: perflutren lipid microspheres)?

From the Guidelines

Perflutren, specifically Definity, is a suitable ultrasound contrast agent for enhancing drug delivery to the eye, particularly when used in conjunction with focused ultrasound application. The use of perflutren in ultrasound-mediated drug delivery to the eye has been explored in various studies, including a systematic review published in 2023 1. This review highlights the potential of commercial microbubbles, such as Definity, in facilitating drug delivery to the eye. Definity microbubbles have been used in studies involving systemic injection in small rodents, with doses ranging from 20 μL/kg to 200 μL/kg, followed by focused ultrasound application to regions of the retina. Some key points to consider when using perflutren for this purpose include:

• The microbubble size and composition, with Definity microbubbles relying on a phospholipid shell containing C3F8 and featuring PEGylated phospholipids for improved circulation and reduced immunogenicity 1.
• The method of administration, which can include peripheral intravenous injection or direct intravitreal injection, with varying doses used in different studies 1.
• The importance of monitoring for potential hypersensitivity reactions and avoiding use in patients with certain conditions, such as right-to-left cardiac shunts or severe pulmonary hypertension. Overall, perflutren, particularly Definity, appears to be a promising agent for enhancing drug delivery to the eye, and its use in this context warrants further exploration and consideration.

From the FDA Drug Label

DEFINITY is an ultrasound contrast agent indicated, after activation, for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border (1)

• Indications for use:
  • Adult and pediatric patients with suboptimal echocardiograms
  • To opacify the left ventricular chamber
  • To improve the delineation of the left ventricular endocardial border
• Administration:
  • Adult Patients: Bolus or infusion
  • Pediatric Patients: Bolus
• Dosage:
  • Adult Patients: 10 microL/kg intravenously over 30 seconds to 60 seconds
  • Pediatric Patients: 3 microL/kg over 30 seconds to 60 seconds
• Contraindications:
  • Known or suspected hypersensitivity to perflutren lipid microsphere or its components
• Warnings and Precautions:
  • Serious cardiopulmonary reactions
  • Hypersensitivity reactions
  • Pain episodes in patients with sickle cell disease The use of perflutren is indicated for patients with suboptimal echocardiograms to improve the visualization of the left ventricular chamber and endocardial border 2.

From the Research

Perflutren Use

• Perflutren is an ultrasound contrast agent used to enhance the visibility of ultrasound images, particularly in the detection of right-to-left shunts 3.
• It is often used in conjunction with transcranial Doppler sonography to detect right-to-left shunts, which can be a cause of refractory hypoxia in critically ill patients 3, 4.
• The use of perflutren with ultrasound contrast agent and transcranial Doppler sonography has been standardized, with recommendations for examination technique and categorization of microbubble count 3.
• Perflutren can also be used with point-of-care echocardiography to evaluate right-to-left cardiopulmonary shunts, allowing for early diagnosis and expedited therapy 4.
• However, there are potential pitfalls to consider when using perflutren, including false-positive and false-negative studies, which can be due to various factors such as congenital abnormalities, mischaracterization of shunts, or pathophysiologic states 4.

Detection of Right-to-Left Shunts

• Right-to-left shunts can be detected using various methods, including transthoracic contrast echocardiography 5, 6, transesophageal echocardiography 3, and point-of-care echocardiography 4.
• The detection of right-to-left shunts is important in the diagnosis and management of pulmonary hypertension, as it can be a cause of hypoxemia and refractory hypoxia 5, 6.
• The use of perflutren with these methods can enhance the visibility of ultrasound images and improve the detection of right-to-left shunts 3, 4.

Pulmonary Hypertension

• Pulmonary hypertension is a condition characterized by elevated mean pulmonary arterial pressure and pulmonary vascular resistance 7.
• It can be associated with various conditions, including congenital heart disease, Eisenmenger syndrome, and pulmonary arteriovenous malformations 7, 5, 6.
• The detection of right-to-left shunts is important in the diagnosis and management of pulmonary hypertension, as it can be a cause of hypoxemia and refractory hypoxia 5, 6.