title: Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial.
abstract: BACKGROUND
  Preliminary evidence suggests a nephroprotective effect of urinary alkalinization in patients at risk of acute kidney injury. In this study, we tested whether prophylactic bicarbonate-based infusion reduces the incidence of acute kidney injury and tubular damage in patients undergoing open heart surgery.
  
  
  RESULTS
  In a multicenter, double-blinded (patients, clinical and research personnel), randomized controlled trial we enrolled 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass. At induction of anesthesia, patients received either 24 hours of intravenous infusion of sodium bicarbonate (5.1 mmol/kg) or sodium chloride (5.1 mmol/kg). The primary endpoint was the proportion of patients developing acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early under recommendation of the Data Safety and Monitoring Committee because interim analysis suggested likely lack of efficacy and possible harm. Groups were non-significantly different at baseline except that a greater proportion of patients in the sodium bicarbonate group (66/174 [38%]) presented with preoperative chronic kidney disease compared to control (44/176 [25%]; p = 0.009). Sodium bicarbonate increased urinary pH (from 6.0 to 7.5, p<0.001). More patients receiving bicarbonate (83/174 [47.7%]) developed acute kidney injury compared with control patients (64/176 [36.4%], odds ratio [OR] 1.60 [95% CI 1.04-2.45]; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90-2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (11/174 [6.3%] versus 3/176 [1.7%], OR 3.89 [1.07-14.2], p = 0.031).
  
  
  CONCLUSIONS
  Urinary alkalinization using sodium bicarbonate infusion was not found to reduce the incidence of acute kidney injury or attenuate tubular damage following open heart surgery; however, it was associated with a possible increase in mortality. On the basis of these findings we do not recommend the prophylactic use of sodium bicarbonate infusion to reduce the risk of acute kidney injury. Discontinuation of growing implementation of this therapy in this setting seems to be justified.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00672334 Please see later in the article for the Editors' Summary.
authors.affiliation: Department of Nephrology and Hypertension, Diabetes, and Endocrinology, Otto-von-Guericke-University Magdeburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
authors.forename: Anja
authors.initials: A
authors.lastname: Haase-Fielitz
authors.forename: Michael
authors.initials: M
authors.lastname: Plass
authors.forename: Hermann
authors.initials: H
authors.lastname: Kuppe
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Claire
authors.initials: C
authors.lastname: Hannon
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Murray
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality / Q000517:prevention & control* / Q000601:surgery; D011518:Proto-Oncogene Proteins / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000150:complications; D017582:Renal Replacement Therapy; D017693:Sodium Bicarbonate / Q000009:adverse effects / Q000627:therapeutic use; D013903:Thoracic Surgery / Q000379:methods; D017211:Treatment Failure; D016482:Urinalysis
chemical_list: D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D017693:Sodium Bicarbonate