Study of contrast-related adverse events leaves some questions lingering

Earlier this year, research in Annals of Emergency Medicine showed that patients who develop an acute kidney injury after contrast-enhanced CT are at an increased risk of major adverse effects within a year.

The findings could be substantial, but there are still too many questions to be sure, argues Richelle J. Cooper, MD, of the UCLA Emergency Medicine Center. 

“Despite a well-articulated rationale for the methods and citation of similar analyses of other data, there remains considerable uncertainty about the study results,” Cooper writes in an editorial, also published in Annals of Emergency Medicine.

In the original study, Alice M. Mitchell, MD, of the Indiana University School of Medicine in Indianapolis, and colleagues examined a year’s worth of patients who received contrast CT and compared the frequency of major adverse events in patients who had contrast-induced nephropathy with those who did not. Major adverse events were defined as, “the combined outcome of death (all causes), renal failure, myocardial infarction, and stroke or other arterial vascular events, in any anatomic territory, requiring invention.”

The authors found that 70 patients developed contrast-induced nephropathy, and 36% of those patients experienced major adverse events. Of the 561 patients who did not develop contrast-induced nephropathy, 12% experienced major adverse events.

“Patients who develop acute kidney injury after contrast-enhanced CT are at increased risk of major adverse events at 1 year,” Mitchell et al. wrote. “This finding supports the need for future studies to definitely determine the cause-and-effect relationship of contrast exposure from contrast-enhanced CT and acute kidney injury and underscores the importance of developing diagnostic imaging strategies that limit patient exposures to iodinated contrast media.”

In the editorial, Cooper details why this analysis resulted in more questions than answers. First, she writes, the design of the original study does not allow a random selection of patients to receive the contrast in question.

“Contrast studies are ordered for specific indications, and physicians often elect to avoid contrast for some patients for a variety of reasons,” writes Cooper.

This, according to Cooper, means the patients receiving contrast agents were believed to truly need the agent, and one can’t assume they are in the same situation as patients who don’t receive the agent.

In addition, Cooper writes that “contrast-induced nephropathy” has certain implications that don’t accurately summarize the situation. Technically, “contrast-associated creatinine-level change” is being studied, because there is a lack of definitive causation at this time.

Cooper also lists five “key questions” that must be answered.

• “When does a change in creatinine level after a contrast exposure merely represent random fluctuation?”
• “When does a change indicate true renal impairment?”
• “When renal impairment occurs, how often is it clinically important as opposed to a transient blip in a surrogate marker that is inconsequential to patient-oriented outcomes?”
• “How often does renal impairment lead to serious long-term adverse outcomes?”
• “If there is clinically apparent renal injury in a patient who receives contrast imaging, could it be that some factor other than the contrast exposure itself explains the renal impairment?”

Overall, Cooper writes, there are ways that this study could be improved, including a focus on more specific variables and a more complicated model.

She notes that the authors cited relevant sources and articulated their findings well, but she believes it is too early to take any definite opinions away from the research.

“Clearly, there is still a long way to go in determining how contrast imaging affects overall outcomes and the lives of the recipients,” Cooper writes.