Prevention of Radiographic-Contrast-Agent–Induced Reductions in Renal Function by Acetylcysteine
This review may be edited
Posted By: A Delaney
Posted Date: 23/5/02
Title: Prevention of Radiographic-Contrast-Agent–Induced Reductions in Renal Function by Acetylcysteine
Authors: Martin Tepel, M.D., Marcus van der Giet, M.D., Carola Schwarzfeld, Ulf Laufer, M.D., Dieter Liermann, M.D., and Walter Zidek, M.D.
Reference: NEJM 2000;343:180-184
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: Background Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown.
Methods We prospectively studied 83 patients with chronic renal insufficiency (mean [±SD] serum creatinine concentration, 2.4±1.3 mg per deciliter [216± 116 µmol per liter]) who were undergoing computed tomography with iopromide, a nonionic, low-osmolality contrast agent. Patients were randomly assigned either to receive the antioxidant acetylcysteine (600 mg orally twice daily) and 0.45 percent saline intravenously, before and after administration of the contrast agent, or to receive placebo and saline.
Results Ten of the 83 patients (12 percent) had an increase of at least 0.5 mg per deciliter (44 µmol per liter) in the serum creatinine concentration 48 hours after administration of the contrast agent: 1 of the 41 patients in the acetylcysteine group (2 percent) and 9 of the 42 patients in the control group (21 percent; P=0.01; relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). In the acetylcysteine group, the mean serum creatinine concentration decreased significantly (P<0.001), from 2.5±1.3 to 2.1±1.3 mg per deciliter (220±118 to 186±112 µmol per liter) 48 hours after the administration of the contrast medium, whereas in the control group, the mean serum creatinine concentration increased nonsignificantly (P=0.18), from 2.4±1.3 to 2.6±1.5 mg per deciliter (212±114 to 226± 133 µmol per liter) (P<0.001 for the comparison between groups).
Conclusions Prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, prevents the reduction in renal function induced by iopromide, a nonionic, low-osmolality contrast agent, in patients with chronic renal insufficiency.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
The authors state that the patients were randomly assigned, but no details of the method of randomisation or the concealment of randomisation is given.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
All 83 patients appear to have been followed up for 48 hours. The data for the 6 day follow up is not fully presented.
2b. Were patients analyzed in the groups to which they were randomized?
Yes, the analysis was done on an intention-to-treat basis.
3. Were patients, health workers, and study personnel blind to treatment?
There is no mention of blinding in the trial. Acetylcysteine has a distinctive odour, so it is unlikely that the patients were blinded, unless the placebo group were given a medication that smelled of rotten eggs!
4. Were the groups similar at the start of the trial?
There were no statistically significent differences in the two groups at baseline.
5. Aside from the experimental intervention, were the groups treated equally?
Yes. Both groups received the same dose of contrast and the same regime of iv fluids. However oral fluid intake was not controlled for.
What are the Results?
1. How large was the treatment effect?
The end point measured was a decline in renal function defined as a rise in serum creatinine of 0.5mg/dL (44micromol/L). A decline in renal function occured in 9/42 (21%) in the control group and 1/41 (2%) of the treatment group.This difference was statistically sigificant P= 0.01 This gives a relative risk reduction of 90%, an absolute risk reduction of 19% and the NNT would be 5.
2. How precise was the estimate of the treatment effect?
The 95% CI for the ARR range from 6% to 32% and so the NNT would be from 3 to 17 patients to prevent one episode of decline in renal function.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
The study population were people with mildly elevated serum creatinine levels which were stable, who required elective CT scanning. There are many patients to whom this could apply. It should be pointed out that patients at risk of acute renal failure (hypotensive, septic etc) were not included and so this data could not yet be extrapolated to an acutley ill population of patients. Only one radiographic contrast agent was used in the trial, and so the results may not be generalisable to all types of radiographic contrast. In order for the results to apply to your patients they would also need to be able to be in hospital for 24 hours for intravenous saline to be administered.
2. Were all clinically important outcomes considered?
I don't think so. A small change in serum creatinine is a surrogate marker for outcome. The patients were not followed to see whether this decline in renal function was sustained past 6 days or lead to the commencement of dialysis at an earlier stage. The decline in renal function as defined was statistically significant, but probably was not clinincally significant. Of note is the fact that no patient required dialysis as a result of reduced renal function. There was no discussion of the cost of admitting all patients at risk of this decline in renal function for at least 24 hours for the intravenous saline administration.
3. Are the likely treatment benefits worth the potential harms and costs?
The reported adverse effects appeared to be similar in both groups, and were relatively mild. At this stage oral acetylcysteine, when used in combination with 24 hours of intravenous saline and liberal oral fluids, in patients with chronic, stable, mildly elevated serum creatinine levels, appears to prevent a decline (in the short term) in renal function associated with the use of a radiographic contrast agent. It would be premature to judge the likely cost-benefit ratio until it can be ascertained that this change in serum creatinine is a marker for a more sigificant clinical outcome. Further study to determine whether this therapy could be used to prevent acute renal failure in an at risk population (hypotensive, septic ...) and to follow-up patients for a longer period to determine whether the decline in renal function is sustained may shed further light onto the clinical utility of this therapy.

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