Sodium Bicarbonate in Cardiac Surgery Study

Summary

With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one of the most common major surgical procedures worldwide (1). Acute kidney injury is a common and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of patients (2-4). Acute kidney injury carries significant costs (4) and is independently associated with increased morbidity and mortality (2,3). Even minimal increments in plasma creatinine are associated with an increase in mortality (5,6). Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed, including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and activation of inflammatory pathways (7-10). COMT LL genotype appears to increase the risk of vasodilatory shock and AKI after cardiac surgery. To date, no simple, safe and effective intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad patient population has been found (11-14). Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also participate in kidney injury. Urinary alkalinization may protect from kidney injury induced by oxidant substances, iron-mediated free radical pathways, complement activation and tubular hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute kidney injury in patients undergoing contrast-media infusion. In a pilot double-blind, randomized controlled trial the investigators found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings. Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney function in patients at increased risk of acute kidney injury undergoing cardiopulmonary bypass needs to be confirmed in an international multicenter, double-blind, randomized controlled trial of intravenous sodium bicarbonate.

Timeline

Start

2008-05

Primary completion

2011-06

Completion

2012-01

Publications

• Elitok S, Kuppe H, Devarajan P, Bellomo R, Isermann B, Westphal S, Kube J, Albert C, Ernst M, Kropf S, Haase-Fielitz A, Haase M. Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial. Anesth Analg. 2021 Dec 1;133(6):1510-1519. doi: 10.1213/ANE.0000000000005741.
• Elitok S, Devarajan P, Bellomo R, Isermann B, Haase M, Haase-Fielitz A. NGAL/hepcidin-25 ratio and AKI subtypes in patients following cardiac surgery: a prospective observational study. J Nephrol. 2022 Mar;35(2):597-605. doi: 10.1007/s40620-021-01063-5. Epub 2021 May 24.
• Haase M, Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Hannon C, Murray PT, Bailey MJ, Bellomo R, Bagshaw SM. Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med. 2013;10(4):e1001426. doi: 10.1371/journal.pmed.1001426. Epub 2013 Apr 16.
• Haase-Fielitz A, Plass M, Kuppe H, Hetzer R, Ostland V, Westphal S, Hoffmann J, Prowle J, Mertens PR, Westerman M, Bellomo R, Haase M. Low preoperative hepcidin concentration as a risk factor for mortality after cardiac surgery: a pilot study. J Thorac Cardiovasc Surg. 2013 May;145(5):1380-6. doi: 10.1016/j.jtcvs.2012.09.003. Epub 2012 Oct 9.
• Haase-Fielitz A, Mertens PR, Plass M, Kuppe H, Hetzer R, Westerman M, Ostland V, Prowle JR, Bellomo R, Haase M. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study. Crit Care. 2011 Aug 4;15(4):R186. doi: 10.1186/cc10339.

Drugs

Indications