Sodium Bicarbonate for Kidney Protection in Cardiac Surgery: Demise of Yet Another Magic Bullet?

Published in The Journal of the American Society of Anesthesiologists 2 2015, Vol.122, 233-235. doi:10.1097/ALN.0000000000000548

Authors: Duminda N. Wijeysundera, M.D., Ph.D.; Chirag R. Parikh, M.D., Ph.D.

ACUTE kidney injury following cardiac surgery is associated with significant morbidity and mortality.  This important postoperative complication, termed cardiac surgery–associated acute kidney injury (CS-AKI), is multifactorial in etiology, with postulated causes including impaired renal perfusion, inflammation, ischemia–reperfusion, microemboli, oxidative stress, and nephrotoxins. Sodium bicarbonate holds theoretical promise for preventing CS-AKI, especially with respect to protecting the vulnerable renal medulla. The medulla receives a disproportionately lower share of renal blood flow (<10% of the total renal blood flow), making it an environment of relative hypoxia and acidosis, where urine first becomes acidic. Sodium bicarbonate has intrinsic natriuretic effects, in addition to its ability to alkalinize tubular fluid. It may therefore increase oxygen delivery and reduce free radical formation by neutralizing acidosis in this ischemic region of the kidney. Improving blood flow and oxygenation, as well as limiting oxidative stress by free radical formation, can help protect the medulla and, thereby, prevent kidney injury. Given this context, the publication of a pilot randomized controlled trial (RCT) in 2009 generated considerable interest.  This relatively small trial of 100 participants found that 4.0 mmol/kg of intravenous sodium bicarbonate administered as an infusion over 24 h significantly reduced rates of CS-AKI. While these initial results were promising, the report appropriately concluded that additional confirmatory trials were needed. In this issue of Anesthesiology, Bailey and colleagues3 address this need in a meta-analysis of three high-quality RCTs, namely the initial 2009 trial and two subsequent larger RCTs.2,4,5 Instead of a traditional meta-analysis that pools the study-levelaggregate data seen in published manuscripts, Bailey et al. performed an individual patient data meta-analysis that combined raw individual-level study data from the three included trials. This statistically more powerful approach allows for a detailed multivariable analysis of the pooled dataset, including testing for subgroup differences. Overall, the investigators found that, despite its early promise, sodium bicarbonate did not significantly reduce the risk of CS-AKI. Nonetheless, subgroup analyses suggested that it might prevent CS-AKI after elective coronary artery bypass graft (CABG) surgery, where large reductions in the risk of severe acute kidney injury were observed.