Tuesday, March 20, 2012

Optimizing strategies for preventing contrast-induced nephropathy

Unfortunately, the motivation for writing this entry was not for the purpose of sharing the findings of a new study, but rather the critical nationwide shortage of sodium bicarbonate, which has left us carefully scrutinizing our strategies for preventing contrast-induced nephropathy (CIN) in patients undergoing cardiac catheterization. For those of you working in a health-system setting, your practice has probably been severely hampered by the growing number of shortages across several therapeutic areas -- hopefully the results from the following study will alleviate some concerns about the need for sodium bicarbonate in the prevention of CIN.

Contrast-induced nephropathy is an unfortunate risk of coronary angiography and it is especially high among patients with existing renal impairment.  Given the extensive use of angiography to evaluate coronary artery disease, strategies to prevent or reduce the risk of CIN have been the subject of ongoing research and unfortunately, the options remain limited.  Oral N-acetylcysteine is no longer recommended (see a summary of the 2012 guidelines for percutaneous coronary intervention here), which leaves intravenous fluid hydration as one of the few remaining alternatives for renoprotection in the setting of cardiac catheterization.  However, the optimal agent recommended for this purpose (i.e., normal saline versus sodium bicarbonate) has not been well-established.

In a study published in late January, Klima, et al [1] randomized 258 patients with renal impairment undergoing intravascular contrast procedures to one of three hydration strategies:
  1. Sodium chloride 0.9% (i.e., normal saline) 1 mL/kg/h for at least 12 hours before and after the procedure
  2. Sodium bicarbonate (166 mEq/L) 3 mL/kg for 1 hour before and 1 mL/kg/h for 6 hours after the procedure; or,
  3. Sodium bicarbonate (166 mEq/L) 3 mL/kg over 20 minutes before the procedure plus oral sodium bicarbonate (500 mg per 10 kg)
Sodium chloride was shown to be superior to sodium bicarbonate at reducing the primary endpoint of change in estimated glomerular filtration rate (eGFR); it was also more effective at reducing the development of CIN, defined as an increase in serum creatinine (SCr) of > 25% or an increase of > 0.5 mg/dL from baseline.  Moreover, the shorter infusion of sodium bicarbonate (20 minutes) plus oral sodium bicarbonate was just as effective as the 7-hour infusion for improving these same endpoints.  No differences were observed in long-term morbidity and mortality or progression to renal replacement therapy.

But does the present study indicate superiority of sodium chloride over sodium bicarbonate?

Not really.

I think the results of this trial only confirms what we've suspected for a long time -- the more hydration around a procedure, the lower the risk of CIN.  That being said, I do think this adds some helpful information to the longstanding debate over which strategy is best for reducing the risk of CIN in the setting of intravascular contrast procedures.

Previous investigations have been rife with limitations.  Furthermore, differences in the types of procedures performed, study populations, and types of contrast dyes utilized have only further complicated efforts to identify a conclusive strategy for renoprotection.  In a recent meta-analysis by Meier, et al, sodium bicarbonate was found to be more effective at reducing CIN; however, effects were less dramatic among patients receiving elective procedures or those receiving iso-osmolar contrast dyes [2].  Another commonly cited study was conducted by Merten et al, where the 7-hour sodium bicarbonate infusion used in the present study was shown to be superior to a 7-hour infusion of sodium chloride [3].  In both instances, no differences in mortality or progression to renal replacement therapy were observed.

I find some comfort in the results of this trial, as it provides us with an alternative for preventing CIN in the setting of a critical nationwide sodium bicarbonate shortage.  However, one remaining question is how long is long enough?  Twelve hours of sodium chloride before and after an intravascular contrast procedure may be more effective than 7 hours of sodium bicarbonate (1 hour before and 6 hours after), but what if the need for catheterization was more urgent (i.e., 4-6 hours or less prior to procedure)? For emergent procedures (i.e., where only < 1 hour of renoprotective measures can be provided prior to procedure), I think we are still compelled to use sodium bicarbonate in the absence of any data stating otherwise.

Secondly, what about patients with moderate to severe heart failure, where excessive intravenous fluid administration could result in clinical decompensation?  Patients with New York Heart Association Class III-IV heart failure were excluded from the present study, and rightly so -- a patient weighing only 70 kg would have received > 1.5 L within a 24-hour period, i.e., definitely enough fluid to promote an exacerbation in a patient with existing heart failure at baseline. In this particular scenario, I think sodium bicarbonate would still be the most attractive option for renoprotection. 

Finally, another interesting finding from the present study is that the shorter course of sodium bicarbonate (20 minutes prior to procedure) combined with oral sodium bicarbonate was just as effective as the 7-hour infusion.  I imagine this strategy would be an attractive option in a number of scenarios, including elective and outpatient intravascular contrast procedures.

At the very least, I think the study by Klima, et al provides us with evidence to support the use of sodium chloride in patients for whom an intravascular contrast procedure is not urgent or emergent.  For these latter scenarios, sodium bicarbonate still appears to be the better option, although it may not be one we can actually use as a result of the ongoing shortage nationwide.  In this case, it appears our only alternative is to hydrate with sodium chloride as much as possible prior to procedure and at least 12 hours afterwards and then hope for the best.

For more information on drug shortages and strategies for addressing them, please see the Drug Shortages Resource Center created by the American Society for Health-System Pharmacists.

  1. Klima T, Christ A, Mueller C, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012 Jan 19.
  2. Meier P, et al. Sodium bicarbonate-based hydration prevents contrast-induced nephropathy: a meta-analysis. BMC Med. 2009 May 13;7:23.
  3. Merten GJ, Burgess WP, Kennedy TP, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. 2004 May 19;291(19):2328-34.


John B, PharmD said...

I enjoy your blog Brent. Keep up the good work.

Wouter said...

What do you think about forced diuresis with matched hydration? Bartorelli and Briguori have shown staggering results with this technique. Reductions up to 70% in high risk patient populations are achieved.

Brent N Reed said...

Could you point me towards some of this data? I would be interested in taking a look.