Preventing Nephropathy Induced by Contrast Medium
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The article by Barrett and Parfrey (Jan. 26 issue)1 raises two clinically relevant points regarding the use of metformin in patients at risk for contrast-medium–induced nephropathy. First, the patient described in the vignette should not have been using metformin, because he already had decreased renal function (estimated glomerular filtration rate, 40 ml per minute per 1.73 m2 of body-surface area), which is a formal contraindication for this medication.2 Second, in patients who do use metformin, the pharmacokinetics of metformin and the clinical course of contrast-medium–induced nephropathy do not support the recommendation of the authors to withhold metformin for the 48 hours before administration of the contrast medium. Metformin has an estimated plasma half-life of 1.5 to 4.9 hours, and 90 percent is eliminated in 12 hours.2 The decrease in renal function does not occur immediately after the administration of contrast medium. Usually the serum creatinine level increases only after 24 to 48 hours and peaks on the second or third day after exposure to a contrast medium.3 On the basis of these data, it is safe to administer metformin until the night before the procedure, thus averting hyperglycemia.
Jorge L. Gross, M.D.
Rogerio Friedman, M.D.
Sandra P. Silveiro, M.D.
Hospital de Clínicas de Porto Alegre
90035-903 Porto Alegre RS, Brazil
jorgegross@terra.com.br
References
Barrett BJ, Parfrey PS. Preventing nephropathy induced by contrast medium. N Engl J Med 2006;354:379-386.
Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-579.
Waybill MM, Waybill PN. Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol 2001;12:3-9.
To the Editor: Barrett and Parfrey state that "it is not necessary to measure the serum creatinine levels of every patient before exposure to a contrast medium." However, looking at the serum creatinine level and the calculated creatinine clearance rate is probably the best clinical way to identify persons at risk for the development of contrast nephropathy. Given the gravity of this complication, it would seem reasonable to obtain these data for all patients before the administration of contrast medium.1
A second concern has to do with the recommendation of normal saline as the fluid of choice for volume expansion before exposure to contrast medium. This regimen, as studied by Mueller et al.,2 showed a low incidence of acute renal failure but an insufficient number of high-risk patients with clinically significant renal failure (i.e., baseline serum creatinine >1.6 mg per deciliter). Merten et al. showed that bicarbonate infusion was superior to normal saline in the prevention of contrast-medium–induced nephro-pathy.3 Clinical logic would favor bicarbonate infusion.4
Richard N. Hellman, M.D.
Indiana University School of Medicine
Indianapolis, IN 46202
rhellman@iupui.edu
References
McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368-375.
Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.
Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.
Chertow GM. Prevention of radiocontrast nephropathy: back to basics. JAMA 2004;291:2376-2377.
To the Editor: Barrett and Parfrey noted some benefit to the use of N-acetylcysteine for the prevention of contrast-medium–induced nephropathy but called for more data before recommending its use. However, newer meta-analyses suggest that prophylaxis with N-acetylcysteine significantly reduces the risk of contrast-medium–induced nephropathy.1,2 For example, Duong et al.2 identified 14 trials of N-acetylcysteine, involving 1584 patients, that were published as full-text articles as recently as November 2004. They reported that the use of oral acetylcysteine resulted in a significant reduction in the risk of contrast-medium–induced nephropathy (pooled relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.84; P=0.01). In these meta-analyses of several newer studies, the use of acetylcysteine for the prevention of contrast-medium–induced nephropathy is strongly supported.
Martin Tepel, M.D.
Charité, Campus Benjamin Franklin
12200 Berlin, Germany
martin.tepel@charite.de
References
Liu R, Nair D, Ix J, Moore DH, Bent S. N-acetylcysteine for the prevention of contrast-induced nephropathy: a systematic review and meta-analysis. J Gen Intern Med 2005;20:193-200.
Duong MH, MacKenzie TA, Malenka DJ. N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis. Catheter Cardiovasc Interv 2005;64:471-479.
The authors reply: Gross et al. raise questions about metformin. Serum creatinine levels above which metformin should be avoided for fear of lactic acidosis are often cited, and indeed, the label for metformin recommends that this agent not be used in women with a creatinine level of 1.4 mg per deciliter or greater or in men with a creatinine level of 1.5 mg per deciliter or greater. However, it should be noted that there are limited data to support any particular level of kidney function below which metformin should not be used; no cases of lactic acidosis were observed during trials of metformin, including one study involving 366 patients with serum creatinine levels ranging from 1.46 to 2.5 mg per deciliter, in which half were randomly assigned to receive metformin for four years.1 The patient in the vignette in our Clinical Practice article had an estimated glomerular filtration rate of 40 ml per minute per 1.73 m2. However, estimates of kidney function not corrected for body-surface area (such as those derived with the Cockcroft–Gault formula) are more appropriate when one is considering the use of drugs. The association between metformin and lactic acidosis may be related to coexisting hypoxic states rather than to the accumulation of metformin with reduced kidney function.2 Our concluding recommendation to withhold metformin for the 48 hours before exposure to the contrast medium was based on some current guidelines, but we agree with Gross et al. that this may not be necessary, as suggested by the Royal Australian and New Zealand College of Radiologists.3 Withholding metformin from the time of administration of the contrast medium is quite defensible and more practical.
Dr. Hellman suggests that serum creatinine needs to be measured in all patients before the injection of a contrast medium. We suggested measuring serum creatinine before all intraarterial injections or in the presence of risk factors for kidney disease. The likelihood of missing a case of abnormal kidney function is low with this less costly approach.4,5 Dr. Hellman also promotes bicarbonate infusions in place of saline infusions to reduce the risk of contrast-medium–induced nephropathy. We do not object to the use of bicarbonate for this purpose, but our review pointed to weaknesses in the current evidence and the need for further research before bicarbonate can confidently be declared superior.
Dr. Tepel recommends N-acetylcysteine to prevent contrast-medium–induced nephropathy. However, the recent meta-analyses cited still show significant differences between trials in the apparent efficacy of N-acetylcysteine, as well as evidence of publication bias. The apparent large benefit with N-acetylcysteine in early studies is not generally borne out by recent trials. These considerations, together with uncertainty about optimal dosing, led us to be cautious in recommending N-acetylcysteine.
Brendan J. Barrett, M.B.
Patrick S. Parfrey, M.D.
Memorial University of Newfoundland
St. John's, NL A1B 3V6, Canada
bbarrett@mun.ca
Since publication of the article, Dr. Barrett reports having served as a consultant for Bracco Diagnostics.
References
Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 2002;13:428-428.
Holstein A, Stumvoll M. Contraindications can damage your health -- is metformin a case in point? Diabetologia 2005;48:2454-2459.
The Royal Australian and New Zealand College of Radiologists. Guidelines for metformin hydrochloride and intravascular contrast media. February 2005. (Accessed April 6, 2006, at http://www.ranzcr.edu.au/collegegroups/reference/EBM/mhicm_guidelines.cfm.)
Choyke PL, Cady J, DePollar SL, Austin H. Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients? Tech Urol 1998;4:65-69. line]
Tippins RB, Torres WE, Baumgartner BR, Baumgarten DA. Are screening serum creatinine levels necessary prior to outpatient CT examinations? Radiology 2000;216:481-484.
Jorge L. Gross, M.D.
Rogerio Friedman, M.D.
Sandra P. Silveiro, M.D.
Hospital de Clínicas de Porto Alegre
90035-903 Porto Alegre RS, Brazil
jorgegross@terra.com.br
References
Barrett BJ, Parfrey PS. Preventing nephropathy induced by contrast medium. N Engl J Med 2006;354:379-386.
Bailey CJ, Turner RC. Metformin. N Engl J Med 1996;334:574-579.
Waybill MM, Waybill PN. Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol 2001;12:3-9.
To the Editor: Barrett and Parfrey state that "it is not necessary to measure the serum creatinine levels of every patient before exposure to a contrast medium." However, looking at the serum creatinine level and the calculated creatinine clearance rate is probably the best clinical way to identify persons at risk for the development of contrast nephropathy. Given the gravity of this complication, it would seem reasonable to obtain these data for all patients before the administration of contrast medium.1
A second concern has to do with the recommendation of normal saline as the fluid of choice for volume expansion before exposure to contrast medium. This regimen, as studied by Mueller et al.,2 showed a low incidence of acute renal failure but an insufficient number of high-risk patients with clinically significant renal failure (i.e., baseline serum creatinine >1.6 mg per deciliter). Merten et al. showed that bicarbonate infusion was superior to normal saline in the prevention of contrast-medium–induced nephro-pathy.3 Clinical logic would favor bicarbonate infusion.4
Richard N. Hellman, M.D.
Indiana University School of Medicine
Indianapolis, IN 46202
rhellman@iupui.edu
References
McCullough PA, Wolyn R, Rocher LL, Levin RN, O'Neill WW. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 1997;103:368-375.
Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336.
Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA 2004;291:2328-2334.
Chertow GM. Prevention of radiocontrast nephropathy: back to basics. JAMA 2004;291:2376-2377.
To the Editor: Barrett and Parfrey noted some benefit to the use of N-acetylcysteine for the prevention of contrast-medium–induced nephropathy but called for more data before recommending its use. However, newer meta-analyses suggest that prophylaxis with N-acetylcysteine significantly reduces the risk of contrast-medium–induced nephropathy.1,2 For example, Duong et al.2 identified 14 trials of N-acetylcysteine, involving 1584 patients, that were published as full-text articles as recently as November 2004. They reported that the use of oral acetylcysteine resulted in a significant reduction in the risk of contrast-medium–induced nephropathy (pooled relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.84; P=0.01). In these meta-analyses of several newer studies, the use of acetylcysteine for the prevention of contrast-medium–induced nephropathy is strongly supported.
Martin Tepel, M.D.
Charité, Campus Benjamin Franklin
12200 Berlin, Germany
martin.tepel@charite.de
References
Liu R, Nair D, Ix J, Moore DH, Bent S. N-acetylcysteine for the prevention of contrast-induced nephropathy: a systematic review and meta-analysis. J Gen Intern Med 2005;20:193-200.
Duong MH, MacKenzie TA, Malenka DJ. N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis. Catheter Cardiovasc Interv 2005;64:471-479.
The authors reply: Gross et al. raise questions about metformin. Serum creatinine levels above which metformin should be avoided for fear of lactic acidosis are often cited, and indeed, the label for metformin recommends that this agent not be used in women with a creatinine level of 1.4 mg per deciliter or greater or in men with a creatinine level of 1.5 mg per deciliter or greater. However, it should be noted that there are limited data to support any particular level of kidney function below which metformin should not be used; no cases of lactic acidosis were observed during trials of metformin, including one study involving 366 patients with serum creatinine levels ranging from 1.46 to 2.5 mg per deciliter, in which half were randomly assigned to receive metformin for four years.1 The patient in the vignette in our Clinical Practice article had an estimated glomerular filtration rate of 40 ml per minute per 1.73 m2. However, estimates of kidney function not corrected for body-surface area (such as those derived with the Cockcroft–Gault formula) are more appropriate when one is considering the use of drugs. The association between metformin and lactic acidosis may be related to coexisting hypoxic states rather than to the accumulation of metformin with reduced kidney function.2 Our concluding recommendation to withhold metformin for the 48 hours before exposure to the contrast medium was based on some current guidelines, but we agree with Gross et al. that this may not be necessary, as suggested by the Royal Australian and New Zealand College of Radiologists.3 Withholding metformin from the time of administration of the contrast medium is quite defensible and more practical.
Dr. Hellman suggests that serum creatinine needs to be measured in all patients before the injection of a contrast medium. We suggested measuring serum creatinine before all intraarterial injections or in the presence of risk factors for kidney disease. The likelihood of missing a case of abnormal kidney function is low with this less costly approach.4,5 Dr. Hellman also promotes bicarbonate infusions in place of saline infusions to reduce the risk of contrast-medium–induced nephropathy. We do not object to the use of bicarbonate for this purpose, but our review pointed to weaknesses in the current evidence and the need for further research before bicarbonate can confidently be declared superior.
Dr. Tepel recommends N-acetylcysteine to prevent contrast-medium–induced nephropathy. However, the recent meta-analyses cited still show significant differences between trials in the apparent efficacy of N-acetylcysteine, as well as evidence of publication bias. The apparent large benefit with N-acetylcysteine in early studies is not generally borne out by recent trials. These considerations, together with uncertainty about optimal dosing, led us to be cautious in recommending N-acetylcysteine.
Brendan J. Barrett, M.B.
Patrick S. Parfrey, M.D.
Memorial University of Newfoundland
St. John's, NL A1B 3V6, Canada
bbarrett@mun.ca
Since publication of the article, Dr. Barrett reports having served as a consultant for Bracco Diagnostics.
References
Rachmani R, Slavachevski I, Levi Z, Zadok B, Kedar Y, Ravid M. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 2002;13:428-428.
Holstein A, Stumvoll M. Contraindications can damage your health -- is metformin a case in point? Diabetologia 2005;48:2454-2459.
The Royal Australian and New Zealand College of Radiologists. Guidelines for metformin hydrochloride and intravascular contrast media. February 2005. (Accessed April 6, 2006, at http://www.ranzcr.edu.au/collegegroups/reference/EBM/mhicm_guidelines.cfm.)
Choyke PL, Cady J, DePollar SL, Austin H. Determination of serum creatinine prior to iodinated contrast media: is it necessary in all patients? Tech Urol 1998;4:65-69. line]
Tippins RB, Torres WE, Baumgartner BR, Baumgarten DA. Are screening serum creatinine levels necessary prior to outpatient CT examinations? Radiology 2000;216:481-484.