A Patient Who Collapsed in Agony After Echocardiography

Catherine Divingian, MD, PhD; Valerie Gironda, MD; Francisco Torano, MD; Jeffrey Jordan, MD


May 19, 2022

UCAs enhance imaging in patients with poor echocardiographic studies, particularly if the left ventricles and apex need to be viewed. These agents are useful for visualization of the endocardium and measurement of the ejection fraction. Additionally, the small size of the microbubbles permits better image resolution compared with saline bubbles. For this reason, UCAs are often the preferred agents, particularly for delineating cardiac wall structures and detecting masses and thrombi, patent foramen ovale, and endocarditis. Visualization of abnormal wall motion is also improved.[1,3,4]

Off-label uses of UCAs have been noted. The gastrointestinal tract, liver, kidneys, spleen, urinary tract, and carotids have been visualized with these agents. Studies of endovascular repair describe the use of UCAs to detect leaks. Documentation has been developed to help clinicians best utilize these agents for alternative applications.[1,5]

In 2007, the risk for adverse cardiac, pulmonary, and allergic reactions to UCAs was first recognized. Most formulations are contraindicated in patients with bidirectional or right-to-left intracardiac shunts, as central nervous system or microvascular occlusions may occur, although they are rare. UCAs should be avoided in patients with acute respiratory distress syndrome or severe pulmonary hypertension. They are also not recommended for patients with hypertensive emergency or urgency. Additional contraindications include New York Heart Association class III or IV heart failure, acute endocarditis, prosthetic valves, and uncontrolled systolic blood pressure.[1,2,3,5]

Hypersensitivity reactions have also been reported; they typically result from a complement activation–related pseudoallergy (CARPA). Allergy and anaphylactoid events are rare but significant. Symptoms can include pruritus, urticaria, shortness of breath, wheezing, angioedema, headaches, nausea, hypotension, and ST-segment elevations secondary to myocardial infarction or coronary artery vasospasm.[1,2,5] These responses are thought to be mediated by mast cells and basophils, which release inflammatory markers; histamines and cytokines are most commonly cited in the literature.[3,5] The patient does not need to be presensitized to the agent to develop these reactions.[3] Additionally, allergies to polyethylene glycol can predispose patients to allergic reactions to some UCAs and are a contraindication to their use.[6]

Deaths have also occurred after the administration of UCAs; however, they were not directly ascribed to the use of contrast agents. Deaths attributed to UCAs remain much lower (4 per 10,000 patients) than those associated with coronary angiography (1 per 100 patients).[5] The US Food and Drug Administration required hazard warnings on the labels of UCAs, which have subsequently been revised as further research has been conducted.[1,2,3]

The safety of UCAs has not been studied in children. Similarly, data on pregnant women are sparse. For these reasons, contrast agents should generally be avoided in these populations whenever possible.[2,5]

The speed of administration may make a difference in the development of some reactions. Bolus administration has been found to result in worse pathophysiologic responses compared with slow infusion of solution, particularly if it has been diluted with water.[2]


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