Back To Square One: Normal Saline For Prevention Of Contrast-Associated Kidney Injury

I was in medical school when the JAMA paper came out that reported superiority with sodium bicarbonate IV fluids over normal saline in preventing contrast-induced acute kidney injury.  This was a Big Deal.  Kidney injury is associated with prolonged hospital stays and increased risk of death.  I recall carefully making a note of the exact sodium bicarb formulation and pre- and post-contrast infusion rates, carrying this index card around in my coat pocket.  Later during residency, I would diligently order the sodium bicarb fluids for high-risk patients pending contrast procedures and spell out the protocol in my chart notes.
A barrage of studies followed the JAMA report but the robust benefit in preventing kidney injury was not replicated.  While some investigators were able to detect a modest benefit with sodium bicarb fluids (for urine alkalinization) or oral N-acetylcysteine (NAC, for scavenging of reactive oxygen species) other groups reported no difference, and small cohort sizes with low outcome rates was a prevailing limiting factor.
The PRESERVE trial (Prevention of Serious Adverse Events Following Angiography) definitively lays to rest all the uncertainties surrounding sodium bicarb and NAC.  In a very anti-climactic fashion.  Sodium bicarb was no better than normal saline, and NAC was no better than placebo.  The study was funded by the Veterans Affairs Cooperative Studies Program and included about 5,000 high-risk patients with stage 3-4 chronic kidney disease (80% were diabetic) from 53 medical centers in the US, Australia, New Zealand and Malaysia.  (I was born and raised in Malaysia, and am simultaneously impressed and bemused that Malaysia was the only Asian country involved in PRESERVE.)  Rates of acute kidney injury were ~9% and death by 90 days ~2.5% across all treatment groups.  PRESERVE trial findings were published in NEJM to coincide with Dr. Weisbord’s presentation at the #AHA17 late-breaking clinical trials session.
I chatted with Dr. Pastor-Soler, a nephrologist from University of Southern California who was the discussant at the media briefing session, expressing my disappointment that we don’t have more effective prevention strategies for contrast-induced kidney injury.  In pragmatic fashion, she pointed out that the PRESERVE trial is important since sodium bicarb fluids often have to be prepared to-order by hospital pharmacies, and there are intermittent shortages plus increased cost.  Based on the PRESERVE trial findings, we can confidently proceed with normal saline which is readily available, with more efficient patient care.  (I’ll make a plug here for Women In Nephrology (WIN) where Dr. Pastor-Soler is President-Elect… if you’re a female in the field of nephrology, consider joining!)
So how much normal saline should we give?  The PRESERVE investigators allowed a great deal of flexibility to participating medical centers: “1 to 3 ml per kilogram of body weight per hour during a period of 1 to 12 hours for a total volume of 3 to 12 ml per kilogram before angiography, 1 to 1.5 ml per kilogram per hour during angiography, and 1 to 3 ml per kilogram per hour during a period of 2 to 12 hours for a total volume of 6 to 12 ml per kilogram after angiography… In patients with a BMI of more than 30, we capped fluid-administration rates on the basis of a weight of 125 kg.”  It sounds like if you give some NS before, during and after, you’re a winner!
To end on a sobering note, the PRESERVE statistics indicate that in high-risk stage 3-4 chronic kidney disease patients who require IV contrast procedures, about 1 in 10 will develop acute kidney injury and 1 in 40 will not survive past 90 days.  Medical necessity for IV contrast should always be carefully weighed.  And normal saline hydration – yes, definitely! – while keeping in mind that 1 liter of NS contains 3.5 grams of sodium and it is prudent to avoid excessive salt/water loading (volume overload being another key predictor of poor hospital outcomes).

Wei Ling Lau Headshot

Wei Ling Lau MD is Assistant Professor in Nephrology at the University of California-Irvine, where she studies vascular calcification and brain microbleeds in chronic kidney disease. She is currently funded by an AHA Innovative Research Grant, and has been a speaker for CardioRenal University and the American Society of Nephrology.