Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Saline hydration prevented nephrotoxicity of radiocontrast agents

ACP J Club. 1995 May-June;122:71. doi:10.7326/ACPJC-1995-122-3-071


Source Citation

Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med. 1994 Nov 24;331:1416-20.


Abstract

Objective

To compare the prophylactic efficacy of saline hydration alone with that of saline hydration plus mannitol or furosemide in patients with chronic renal insufficiency who are scheduled for cardiac angiography.

Design

Randomized controlled trial of 48 hours' duration.

Setting

Tertiary care center.

Patients

78 patients (mean age 63 y, 69% men) scheduled for cardiac angiography who had a serum creatinine concentration > 140 µmol/L or creatinine clearance < 60 mL/min. Follow-up was complete.

Intervention

Starting 12 hours before angiography, patients received 0.45% intravenous (IV) saline, 1 mL/kg body weight per hour until 12 hours after angiography. The infusion was either continued alone during the angiography (n = 28) or supplemented with 25 g of mannitol IV 60 minutes before angiography (n = 25) or with 80 mg furosemide IV 30 minutes before angiography (n = 25). The types of radiocontrast agents and the number of patients with diabetes mellitus or congestive heart failure were equally divided among groups.

Main outcome measure

Decrease in renal function (increase in baseline serum creatinine concentration of ≥ 44 mmol/L within 48 hours after injection of radiocontrast medium).

Main results

At 24 hours after angiography, the mean increase in serum creatinine concentration was 17.7 µmol/L in the mannitol group and 26.5 µmol/L in the furosemide group compared with 0.0 µmol/L in the saline-only group (P = 0.01 and 0.002, respectively). At 48 hours, the mean increase in serum creatinine concentration was 26.5 µmol/L in the mannitol group and 44.2 µmol/L in the furosemide group compared with 8.8 µmol/L in the saline-only group {95% CI for the 17.7 µmol/L difference between saline and mannitol, 4.1 to 40.4 and CI for the 35.4 µmol/L difference between saline and furosemide, 8.5 to 62.2}*. The serum creatinine concentration increased by ≥ 44.2 µmol/L (0.5 mg/dL) in more patients in the furosemide group than in the saline-only group (Table); the mannitol and saline-only group did not differ (P = 0.2).

Conclusion

Hydration with saline alone was associated with a lower incidence of radiocontrast-induced renal dysfunction than hydration with saline plus furosemide in patients with renal dysfunction who were having angiography; hydration with saline alone did not differ from hydration with mannitol.

Source of funding: Baxter HealthCare Corporation.

For article reprint: Dr. R. Solomon, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA. FAX 617-732-2467.

*Numbers calculated from data in article.


Table. Hydration with saline plus furosemide vs saline only in patients with chronic renal insufficiency who were scheduled for cardiac angiography†

Outcomes at 48 h Saline plus furosemide Saline only RRI (95% CI) NNT (CI)
Decreased renal function† 40% 11% 273% (27 to 1067) 4 (2 to 17)

†Abbreviations defined in Glossary; RRI, NNT, and CI calculated from data in article.
†Increase in serum creatinine concentration ≥ 44 mmol/L within 48 hours after angiography.


Commentary

Until recently, few data existed about the use of diuretics in humans to prevent radiocontrast nephropathy. On the basis of animal studies, however, the addition of mannitol or furosemide, or both, to saline prophylaxis was accepted clinical practice (1). Now, Solomon and colleagues convincingly show that furosemide and mannitol may increase the incidence of acute renal failure in a high-risk group. This confirms a previous study of furosemide in humans (2), although the potential deleterious effects of mannitol remain controversial (3).

Why are mannitol and furosemide deleterious? The temptation is to assume that they are deleterious as a result of diuresis; in this study, however, weights and urine outputs were similar in all groups. Thus, the definition of the pathophysiology awaits additional study.

On the basis of the results of Solomon and colleagues and other recent studies (2-4), prophylaxis should be approached as follows: Identify high-risk groups—those with chronic renal insufficiency, diabetes mellitus, myeloma, cirrhosis, nephrosis, and volume depletion. In high-risk patients, treat with 0.45% saline IV as described in this study, monitoring intake and output closely. Avoid diuretics, if possible, especially in patients with diabetes (3), and use low-osmolality radiocontrast agents (4).

Gregory K. Buller, MD
St. Mary's HospitalWaterbury, Connecticut, USA


Commentary Update

Probably the most significant adverse effect of radiocontrast agents is the development of acute renal failure (ARF). Although the risk of this complication can be reduced by the administration of IV saline and avoidance of diuretics (5, 6), ARF can still occur. Tepel and colleagues (7) have recently examined the use of an antioxidant, acetylcysteine, to prevent radiocontrast-induced ARF. In a prospective, randomized evaluation of 83 patients at substantial risk for ARF, those investigators compared the use of acetylcysteine, 600 mg twice daily given the day before and the day of radiocontrast administration, plus 0.45% saline, 1 mL/kg of body weight/hour for 12 hours before radiocontrast and continuing 12 hours afterwards, with saline alone (plus placebo). The relatively astounding result was that acetylcysteine markedly reduced the incidence of ARF (1 of 41 patients vs 9 of 42 patients in saline alone group). It also reduced serum creatinine significantly from baseline, which may have implications for its study in patients with various forms of chronic renal failure (CRF). There were no apparent negative side effects of acetylcysteine.

The Tepel study is small (only 10 end points altogether) and may overtake the benefits, understate the adverse effects, or be otherwise misleading. Nevertheless, it is worth considering in prophylaxis against radiocontrast-induced ARF.


References

1. Cronin RE. Radiocontrast media-induced acute renal failure. In: Schrier RW, Gottschalk LW, eds. Diseases of the Kidney. Boston: Little, Brown and Co.;1993;1187-201.

2. Weinstein JM, Heyman S, Brezis M. Potential deleterious effect of furosemide in radiocontrast nephropathy. Nephron. 1992;62:413-5.

3. Weisberg LS, Kurnick PB, Kurnick BR. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney Int. 1994;45:259-65.

4. Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high-and low-osmolality iodinated contrast media. Radiology. 1993;188:171-8.

5. Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med. 1994;331:1416-20.

6. Buller G. Commentary on “Saline hydration prevented nephrotoxicity of radiocontrast agents.” ACP J Club. 1995;122:71. Abstract and comment on: Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med. 1994;331:1416-20.

7. Tepel M, van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343:180-4.