The sodium bicarbonate regimen was the same as that reported by Merten in 2004—namely, 154 mEq/L of sodium bicarbonate in 5% dextrose solution, given at 3 mL/kg/hr for one hour before contrast administration and 1 mL/kg/hr for six hours afterward. The saline regimen (154 mEq/L) was the same as that reported by Mueller in 2002—1 mL/kg/hr for 12 hours before contrast administration and 12 hours afterward. All patients received NAC at a dose of 1,200 mg twice daily the day before and the day of contrast administration. It is not possible to conclude from this trial whether sodium bicarbonate without NAC would have been as effective as the regimen studied. Ascorbic acid was included in this trial as another antioxidant to compare with NAC. The three other RCTs published in 2007 are summarized in Table 3 (see p. 21).11,12,13
Recently, two large RCTs of saline versus bicarbonate concluded there was no difference between the two.14,15 These trials were the largest to date, each of them single center and unblinded, and using slightly different methods than the REMEDIAL trial. CIN also was defined more broadly as a 0.5mg/dL or 25% change in creatinine within five days after contrast. Follow-up was only 88% in one trial. Nevertheless, these two new trials reach quite different conclusions than those before. Table 3 (see p. 21) summarizes seven RCTs of saline versus bicarbonate in the prevention of CIN. Differences in design and methods, definitions of CIN, completeness of follow-up, and severity of renal dysfunction among patients studied, make direct comparisons among these trials difficult. But as five of the seven RCTs of saline versus bicarbonate have concluded that bicarbonate is superior, and none have concluded saline is superior, this author recommends that at the present time intravenous sodium bicarbonate be used according to the Merten protocol when providing IVF for the prevention of CIN.
Back to the Case
The patient in the vignette has an estimated GFR of about 32 mL/min by the MDRD equation. With this level of renal dysfunction, the presence of diabetes mellitus, mellitus and assuming at least a 100 cc contrast bolus with the angiography, her risk for CIN is about 14% (eight points on the Mehran scale illustrated in Table 21). Alternatives to coronary angiography are limited in this example, and pharmacologic and IVF measures to prevent CIN are indicated. Borrowing from the regimen used in the REMEDIAL trial, she should ideally receive NAC 1200 mg orally BID for two days, starting one day prior to the procedure (in this case, would begin as soon as the risk for CIN is appreciated and continue for four doses). More importantly, she should receive sodium bicarbonate 154mEq/L at a rate of 3 mL/kg/hr one hour prior to contrast and 1 mL/kg/hr during and for six hours following the contrast procedure.
Bottom Line
Contrast nephropathy risk varies inversely with GFR and can be estimated according to a validated tool. Patients at risk for CIN should be identified early and offered NAC and sodium bicarbonate, if there are no alternatives to administering intravenous contrast. Intravenous saline also is effective, but may not be as effective as bicarbonate. TH
Dr. Anderson is an assistant professor of medicine at the University of Colorado Denver and the associate chief, Medical Service, at the Denver VA Medical Center.
References
1. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44:1393-1399.
2. 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;343:180-184.