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Contrast Media Use in High-Risk Patients
Contrast-induced nephropathy (CIN) has traditionally been somewhat ignored. Only in the last few years has there been some light shed on this complication. We knew as early as 10 years ago, when the first published literature came out on CIN in the percutaneous coronary intervention (PCI) population, that the incidence of CIN after receiving contrast media was somewhere around 14-15% of the PCI population in the contemporary cath lab setting. Unfortunately, it really wasn’t until about 5 years ago that we really began to pay a great deal of attention. Now, as you know, it’s become a very important topic, because CIN is an important complication. It could be as high as 50% of the population if diabetes and chronic kidney disease are present, and it could be as low as 1–2% if there are few to no risk factors. If we look at a cross-section of the PCI population, the rate of CIN falls somewhere between 14–16%.
What about acute myocardial infarction patients?
In an acute myocardial infarction (MI) setting, we don’t know the patient’s baseline creatinine, so it’s very difficult to ascertain their risk profile. We have developed a risk score that helps to identify patients at risk (Figure 1), but if someone comes in with an acute MI, it’s difficult to fill in all of the integers, because you don’t know their baseline creatinine and their creatinine clearances, and they are just going directly into the cath lab. A paper was published by Dr. Bartorelli’s group in Italy, where they gave the patient intravenous doses of N-acetylcysteine in acute MI (1200 mg IV bolus). They administered it twice daily and those patients actually did quite well,1 but it’s a small study.
In an acute MI setting, the most important thing is to assume that everyone is at risk for CIN. Try to limit patient contrast media exposure. Be very judicious about treating patients; really, that should hold for every case. We should be trying to give as little contrast media as possible to our patients. In addition, we need to keep patients as well-hydrated as they can stand both during and after the procedure, because hydration is the one element that we know helps these patients. helps to identify patients at risk (Figure 1), but if someone comes in with an acute MI, it’s difficult to fill in all of the integers, because you don’t know their baseline creatinine and their creatinine clearances, and they are just going directly into the cath lab. A paper was published by Dr. Bartorelli’s group in Italy, where they gave the patient intravenous doses of N-acetylcysteine in acute MI (1200 mg IV bolus). They administered it twice daily and those patients actually did quite well,1 but it’s a small study. In an acute MI setting, the most important thing is to assume that everyone is at risk for CIN. Try to limit patient contrast media exposure. Be very judicious about treating patients; really, that should hold for every case. We should be trying to give as little contrast media as possible to our patients. In addition, we need to keep patients as well-hydrated as they can stand both during and after the procedure, because hydration is the one element that we know helps these patients.
What is the difference between low-osmolar and iso-osmolar contrast media?
Contrast media can be difficult to understand. The compounds have multiple characteristics and one important characteristic is the osmolality. The label “low-osmolar” leads many to assume it must be the lowest osmolality, but in fact “iso-osmolar” media are the lowest osmolality. High-osmolar compounds, with an osmolality over 1200, like HiPeg, no longer even exist. Most of our contrast media are actually low-osmolar compounds, but they are still at twice the osmolality of the iso-osmolar compound. The single iso-osmolar agent we have is Visipaque (iodixanol). It is iso-osmolar to blood, about 297 or 300 milliosmoles.
Differences between contrast media are also attributable to their chemical properties. Compounds are differentiated by ionicity and whether they are monometer or dimer, which has to do with the number of benzene rings. Ionicity is related to the carboxyl group. So, it is not just osmolality that differentiates a certain contrast media. Viscosity (thickness) is another important quality that is not widely discussed. Ultimately, when studying contrast media, one needs to take into consideration all of these qualities, not just the osmolality.
How does the viscosity of a contrast agent affect the body?
The most viscous compound available is the iso-osmolar non-ionic agent, which is iodixanol. That agent, while having the lowest osmolality, has the highest viscosity. There have been some studies that have shown that viscosity may be actually more detrimental to the kidneys than osmolality. In the Cardiac Angiography in Renally Impaired Patients (CARE) trial, which compared low-osmolar contrast agents iopamidol (Isovue) and ioxaglate (Hexabrix) with iodixanol (Visipaque) in 414 high-risk patients undergoing angiography, there was actually a trend toward a benefit for the low-osmolar compound as opposed to (iso-osmolar) iodixanol. In fact, in diabetic patients, that trend was even stronger. So I think viscosity does make a difference.
Having said that, we also need to consider that iodixanol has been studied in the Contrast Media Utilization in High Risk PTCA (COURT) trial, in close to a thousand patients. Investigators looked at ischemic components and major adverse cardiac events (MACE), which is actually a very strange endpoint — a mishmosh and the kitchen sink, I call it, since MACE is not really just death, MI and revascularization, but a lot of other things. The data showed that iodixanol was better for that major composite endpoint in large numbers of patients. However, this trial did not look at CIN. It was published in 2000 and there was not the focus on contrast nephropathy at that time.
How should the CARE trial affect clinical practice?
We have a major problem on our hands, which is that right now, in the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for acute coronary syndromes, we are told to use Visipaque (iodixanol) for PCI. Having this specific recommendation, when clinicians are very much guideline-oriented these days, means that the CARE trial results may not be properly integrated into actual practice. The CARE trial now gives us a large enough data set to say that perhaps the clinical difference between the iso-osmolar and the low-osmolar agents doesn’t exist. Iodixanol (Visipaque) may not be superior for the prevention of contrast nephropathy. That’s an important statement. The trial results do not claim superiority for any one agent. The CARE trial shows only that low-osmolar agents are not worse and that there is probably no clinical significance between the two types in the prevention of contrast-induced nephropathy, given the small sample size of the CARE trial.
In your own practice, how have the recent CARE trial results and other data affected your decisions about contrast media?
I am now convinced that the low-osmolar compounds may be just as effective as iso-osmolar compounds in prevention of CIN.
Can you talk more about the dangers of high contrast volumes?
I think the volume of contrast media is one of the most important considerations in avoiding CIN, maybe even more important than the type of contrast media utilized. Ask yourself: Did we hydrate the patient? Did we assess their risk? Did we take all of the integers in Figure 1 into consideration? Look at the patient as a whole and then do everything you possibly can to protect them from CIN by hydrating, assessing risk, not giving too much contrast volume and so on. In every presentation I make, I stress these points.
What are some of the typical concerns brought up when you speak about this issue?
There are a lot of people who truly believe that the iso-osmolar compound is superior to the low-osmolar. There are a lot of people who believe that N-acetylcysteine works. There are many who believe that bicarbonate hydration works. Finally, there are those of us who believe that none of these things make that much of a difference. It’s great that we have all of these data, but the most effective thing we can do is go back to the basics and look at the patient, assess their risk, hydrate them when we can and use as little contrast media as possible.
What have you found to be an effective method to reduce contrast volume use?
We have made a big impact simply by having people recognize CIN as an important complication and also hydrating the patients. The rates of contrast nephropathy have decreased tremendously in our own institution. We are now at about 7%, and we used to be at 16%. The one thing we have done is to pay a lot of attention to patient risk and hydration. We bring high-risk patients in the night before, keep them an extra day post procedure to make sure they are well-hydrated and watch their creatinine levels.
What needs to be done to answer some of the remaining questions about contrast media and CIN?
I would like to see a larger trial. Unfortunately, no one is going after the large trials. Of all of the trials we are seeing, the biggest problem is that they are quite small. Larger trials with real answers would be great.
Dr. Roxana Mehran can be contacted at rmehran@crf.org
