Product safety compromises patient safety (an unjustified black box warning on ultrasound contrast agents by the Food and Drug Administration).

摘要

In October 2007, the United States Food and Drug Administration (FDA) issued an alert requesting "black-box" warnings on the perflutren-based ultrasound contrast agents Definity (Bristol-Myers Squibb Medical Imaging, North Billerica, Massachusetts) and Optison (Amersham Health, Amersham, UK). Additionally, the FDA recommended that these agents "be contraindicated in patients with unstable cardiopulmonary status, including patients with unstable angina, acute myocardial infarction (MI), respiratory failure, or recent worsening congestive heart failure." According to the FDA's Web site, there have been postmarketing reports of 10 deaths after the administration of Definity and 1 after the administration of Optison. At least 6 of these occurred 1 to 12 hours after dosing and were attributed to serious underlying conditions and/or other medications. Four fatal cases, however, occurred <30 minutes after the administration of Definity: 1 after a stress test, 2 in patients with severe heart failure, and 1 in a ventilated patient with severe respiratory failure, sepsis, and multiple pulmonary emboli. These 4 deaths occurred over a 6-year period. During that period, >2 million doses were administered (Bristol-Myers Squibb Medical Imaging, personal communication). Thus, the fatal event rate was approximately 1 in 500,000. This rate is far less than the fatal event rate of a treadmill exercise test (1 in 2,500) or a transesophageal echocardiogram (1 in 10,000). In fact, this extremely low event rate testifies to the safety of these agents, considering that they are frequently used in critically ill patients. It is almost certain that the 4 fatal cases were consequences of severe underlying cardiovascular disease and were not caused by the contrast agent.