Rochester, MN - Baking soda has a lot of uses, but is there one too many? Perhaps, according to a retrospective look at >11 000 radiographic imaging cases in which sodium bicarbonate, increasingly given intravenously to prevent contrast-induced nephropathy (CIN) in patients undergoing CT or angiography, seemed actually to cause the serious complication rather than protect the kidneys [1].

The analysis casts doubt on a practice that has won the esteem of practitioners based primarily on one small randomized trial [2] with important limitations, according to the new study's authors, led by Dr Aaron M From (Mayo Clinic, Rochester, MN) and colleagues.

"The clinical use of sodium bicarbonate for renal protection should be reconsidered until further investigation can elucidate its proper use," the group writes in the January 2008 issue of the Clinical Journal of the American Society of Nephrology.

In another finding from the study, no increased CIN risk was observed among patients treated with another agent frequently given for renal protection, N-acetylcysteine, or those who received both that agent and sodium bicarbonate.

Sometimes when you study these agents in a real-world population, you find something different from [what you would] studying them in a randomized trial.

Speaking to heartwire, From said his group has documented an "exponential increase" in the use of sodium bicarbonate prophylaxis immediately after the 2004 publication of a 119-patient randomized study from Merten et al, in which CIN developed in 13.6% of patients hydrated with saline only but in only 1.7% of those who received sodium bicarbonate (p=0.02).

"Sodium bicarbonate is now the standard of care at our institution," Merten coauthor Dr W Patrick Burgess (Carolinas Medical Center, Charlotte, NC) told heartwire when the study was published. "We have not dialyzed a patient for contrast nephropathy for a year and a half. And that's unheard of."

An informal survey of heartwire stories as well as reviews and original studies on Medline appearing since the Merten publication does suggest that interventional cardiology has embraced the use of sodium bicarbonate, often combined with N-acetylcysteine, for CIN prophylaxis. Recommendations for preventing CIN published by the Society of Cardiovascular Angiography and Interventions in 2006 cautiously recommend sodium bicarbonate in high-risk cases [3].

But Merten et al, From said, "were very selective about the patients they included, and in our study we used a real-world population." It consisted of 7911 adult patients encompassing 11 516 cases of contrast administration, almost always with a low-osmolar nonionic agent, for which there were both pre- and postprocedure creatinine readings but no preprocedure elevations of >8 mg/dL and no history of dialysis. Thoracic and abdominal CT accounted for more than three-fourths of the imaging procedures, and coronary angiography and interventions most of the rest.

In an analysis that adjusted for "known and hypothesized" predictors of CIN, the odds ratio for CIN among patients getting sodium bicarbonate alone was 3.10 (95% CI 2.28-4.18, p<0.001) compared with no prophylaxis and 2.73 (95% CI 1.86-3.97, p<0.001) compared to N-acetylcysteine alone. The covariates included hydration volume; use of beta blockers, diuretics, nonsteroidal anti-inflammatory drugs, ACE inhibitors, angiotensin-receptor blockers, or aspirin; age; sex; preprocedure creatinine; contrast iodine load; prior exposure to contrast agents; type of imaging study; and heart failure, hypertension, renal failure, multiple myeloma, or diabetes mellitus.

The CIN risk with sodium bicarbonate alone vs no prophylaxis was significantly increased whether or not it was administered according to the same protocol used in the Merten study, the authors observe.

On the other hand, From acknowledged when interviewed, his group's patients usually received contrast agents intravenously for noncoronary and noncardiac CT imaging. That's unusual for a study on contrast nephropathy, he said, and distinguishes them Merten et al's patients, most of whom received contrast agents intra-arterially at cardiac catheterization. But CT is a growth area in cardiac imaging, he observes.

Besides, there are randomized-trial data based on patients undergoing coronary angiography showing no protective effect from sodium bicarbonate. For example, the MEENA trial, presented by Dr Somjot S Brar (Kaiser Permanente, Los Angeles, CA) at the i2 Summit at the American College of Cardiology 2007 Scientific Sessions, was a randomized comparison of hydration strategies based on sodium chloride in 156 patients and sodium bicarbonate in 147 patients exposed to a nonionic, low-osmolar contrast agent at coronary angiography. The rate of CIN, defined as at least a 25% decrease in glomerular filtration rate, was 13.5% in both groups, which had been similar at baseline with respect to demographics, comorbidities, and medication use and periprocedurally with respect to procedure duration, contrast volume used, how often N-acetylcysteine was also given, and prevalence of same-session PCI.

By the 30-day follow-up, one patient—in the saline-hydration arm—had gone on dialysis. There had been two deaths in the saline group and three in the sodium bicarbonate group, not a significant difference.

"It was odd that [sodium bicarbonate] was adopted so quickly without much data," From commented. Usually such an innovation would take several randomized controlled trials or at least one very large one, he said. "I think people thought that it would be helpful and that there would be no harm." His group's findings are "a warning that sometimes when you study these agents in a real-world population, you find something different from [what you would] studying them in a randomized trial."