A spokesman for the FDA said, “the letter has been received, and the agency is working on a response.” The agency had no further comment on the issue.
“The near-term result of this black box warning, in my opinion, will be a dramatic drop in the use of ultrasound contrast agents, and as a result, the quality of echocardiograms will go down until this scare wears off,” Dr. Peter S. Rahko said in an interview.
“The reaction of the FDA and the rules they imposed seem to be excessive,” said Dr. Rahko of the departments of medicine and public health and director of the adult echocardiography laboratory at the University of Wisconsin, Madison.
But Dr. Rahko does agree with the FDA's expressed concerns that an unknown proportion of patients may suffer allergic reactions to the microsphere contrast agents, which has occurred on a few occasions at Wisconsin.
When the black box warning was issued, the use of contrast-enhanced ultrasound ceased at the University of Wisconsin and other centers. The Wisconsin team developed a two-stage screening protocol for stable and critically ill patients (see box), said Dr. Rahko, who was one of the original investigators in the Definity trials but has no financial conflicts related to the topic.
Visualization of a left ventricular thrombus is clearer in an echocardiogram with contrast (right) than in a noncontrast image. IMAGES COURTESY DR. PETER S. RAHKO/UNIVERSITY OF WISCONSIN HOSPITAL
Adjusting to the Black Box Alert
After the FDA issued its warning on ultrasound contrast agents, Dr. Rahko and his colleagues at the University of Wisconsin halted their practice of automatically ordering contrast following a bad-quality echocardiogram.
Previously, “If the patient was appropriate, then the contrast could be administered in the intensive care unit with the assistance of nursing personnel and others taking care of the patient,” Dr. Rahko said.
The hospital now operates with a more costly and time-consuming two-tiered protocol that is tailored to stable and unstable patients undergoing echocardiography.
For an unstable hospitalized patient, the baseline sonogram is read by a cardiologist; if it's of poor quality and a redo with Definity seems appropriate, the cardiologist recommends that the study should be repeated with contrast. “The patient care team now becomes the responsible party ordering the contrast.”
The protocol for stable patients scheduled for echo in the inpatient or outpatient setting shifts responsibility for the final decision to the patient and includes screening for conditions that might contraindicate the use of the microspheres. “Our nurses—in the echo lab or at other sites—screen the patients using oxymetry to make sure that oxygen saturation levels are appropriate and that patients don't have significant hypoxia or lung disease,” Dr. Rahko explained.
Patients who are stable and cleared for a contrast injection are given an information sheet that explains the procedure, why it's being done, and the risks it poses. The patient then decides whether or not to proceed. And “we keep the patient under direct observation for 30 minutes, in case of an allergic reaction,” he said.