Early Bolus of Sodium Bicarb Reduces Contrast Nephropathy in Emergent PCI

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A rapid bolus injection of sodium bicarbonate immediately before contrast use drastically reduces the rate of contrast induced nephropathy (CIN) compared with sodium chloride in patients with mild renal dysfunction scheduled to undergo emergency angiography or percutaneous coronary intervention (PCI), according to a small randomized trial published online February 25, 2011, ahead of print in the American Journal of Cardiology.

Normally, sodium bicarbonate is given as an infusion over time in such patients, when possible. According to the authors, sodium bicarbonate in bolus form has been shown beneficial in elective PCI patients, but not emergent ones.

Researchers led by Hiromichi Ueda, MD, of Osaka General Medical Center (Osaka, Japan), looked at 59 consecutive patients with renal insufficiency (serum creatinine [SCr] > 1.1 mg/d) who were undergoing an emergent diagnostic or interventional coronary procedure at their institution. The patients were randomized to an IV bolus injection of sodium bicarbonate (154 mEq/L; Otsuka Pharmaceutical, Tokyo, Japan) or sodium chloride (0.5 ml/kg) as soon as possible after admission and prior to contrast administration. Afterward, all patients received an IV infusion of 154 mEq/L sodium bicarbonate at a dose of 1 mL/kg/hr during and for 6 hours following the procedure.

The majority of the patients presented with AMI or unstable angina, with no significant differences seen between the 2 groups in terms of baseline characteristics. The primary endpoint of CIN (defined as an increase in SCr > 0.5 mg/dl or > 25% over baseline within 2 days) was markedly reduced with sodium bicarbonate, as was SCr at discharge and at 2 days post procedure (table 1).

Table 1. Post Procedural Outcomes

 

Sodium Bicarbonate
(n = 30)

Sodium Chloride
(n = 29)

P Value

CIN at 2 Days

3.3%

27.6%

0.01

SCr at 2 Days, mg/dl

1.38 ± 0.60

1.91 ± 1.19

0.04

SCr at Discharge, mg/dl

1.33 ± 0.43

1.94 ± 1.13

0.01

Abbreviations: CIN, contrast induced nephropathy; SCr, serum creatinine.

Length of hospital stay was similar between the groups (21 to 23 days). In terms of clinical outcomes, the overall incidence of adverse events (congestive heart failure, acute renal failure requiring dialysis, lethal arrhythmia, and death) was similar between the sodium bicarbonate (30%) and sodium chloride (34%) groups (P = 0.72). There were a total of 5 in-hospital deaths, 2 in the sodium bicarbonate group and 3 in the sodium chloride group.

On multivariable logistic regression analysis randomization to sodium bicarbonate was the only independent predictor of a reduction in CIN (OR 0.03; 95% CI 0.001-0.80; P = 0.04).

Study Halted Early

The trial originally was intended to enroll a total of 80 patients, but it was stopped early when significant differences were found between the 2 groups. The decision was based on ethical concerns over exposing the control group to a greater risk of CIN by withholding the bolus injection of sodium bicarbonate.

“The results from the present study have demonstrated that a bolus injection of sodium bicarbonate was more effective than that of sodium chloride for the prevention of CIN in patients with mild [chronic kidney disease] undergoing emergent coronary procedures,” the researchers conclude.

In terms of a potential mechanism, the authors note that sodium bicarbonate may inhibit the development of free radical renal injury through alkalization of the renal tubular fluid. In particular, rapid alkalization as occurs with bolus injection of sodium bicarbonate, could strongly inhibit oxygen free radical production in acidic conditions such as during an emergent coronary procedure.

Good Strategy, Questionable Data

According to Richard J. Solomon, MD, of the University of Vermont (Burlington, VT), giving an early bolus to emergent patients before contrast administration makes sense. “For these urgent cases, certainly for people who have STEMI, the goal is to get them into the cath lab as quickly as possible, so you don’t have time to delay while the pharmacy is making up a bicarb solution,” he told TCTMD in a telephone interview. “What the authors are suggesting is that there’s a rapid way to give bicarb. Well, that seems like a reasonable strategy. I just don’t know if their data are believable.”

Two aspects of the trial proved major stumbling blocks for Dr. Solomon: the small number of patients and early termination of the study. “They should not have stopped it prematurely,” he said. “That’s sort of a no-no in clinical research unless you have a significant adverse event. CIN wouldn’t qualify as that.”

In a telephone interview with TCTMD, Somjot S. Brar, MD, of Kaiser Permanente (Los Angeles, CA), agreed that “the concept is interesting. There are some patients who you can’t pre-treat because of the way they present. You don’t have the hour or hours to hydrate them. A therapy targeted to that vulnerable population would be desirable, but whether there’s enough evidence to support this intervention as something to fill that void, I seriously doubt it.”

CIN Literature ‘Notorious’

Like Dr. Solomon, the small size of the study also proved troubling to Dr. Brar. So did the magnitude of the benefit seen in the treatment group. “The contrast nephropathy literature is almost notorious for having small, very positive trials that then get refuted later. That story has repeated itself with N-acetylcysteine, sodium bicarb, fenoldopam. We’ve seen it over and over,” Dr. Brar said. “Really, just one extra event in the treatment group with sodium bicarb would have been enough to make a significant difference in the results and conclusion, so when you’re dealing with a margin of error that slim with very positive results from a small trial, we tend to interpret them pretty cautiously.”

Dr. Brar also questioned the aggressiveness of the study’s statistical assumptions in looking for an absolute reduction of 20% in the primary endpoint. “There’s almost nothing that we power these days that yields an absolute reduction of 20%,” he said. “Even the large CIN trials were powered for an absolute reduction on the margins of 10%. This study is assuming a very profound treatment effect, and with what we know about the CIN literature, my biggest concern is that this is a false-positive result from a small study.”

That is not to say the strategy should not be explored further, Dr. Brar noted. “It’s potentially worth looking at,” he said. “The protocol is different from others in that you’re giving [sodium bicarbonate] all at once, and if you’re doing that, it may in theory potentiate the attenuation of free radicals since you have a large dose given at the time of contrast. It probably is worthwhile exploring it further in a larger study.”

Dr. Solomon agreed that the concept deserves a larger trial. “I think it’s interesting. I’m just not going to tell people to do this based on these 59 patients,” he said.

 


Source:
Ueda H, Yamada T, Masuda M, et al. Prevention of contrast-induced nephropathy by bolus injection of sodium bicarbonate in patients with chronic kidney disease undergoing emergent coronary procedures. Am J Cardiol. 2011;Epub ahead of print.

 

Disclosures:

  • Dr. Ueda makes no statement regarding conflicts of interest.
  • Drs. Solomon and Brar report no relevant conflicts of interest.

 

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