Email updates

Keep up to date with the latest news and content from Critical Care and BioMed Central.

Highly Accessed Commentary

Sodium bicarbonate to prevent cardiac surgery-associated kidney injury: the end of a dream?

Jean-Michel Hougardy1 and Daniel De Backer2*

Author Affiliations

1 Department of Nephrology and Erasme University Hospital, Université Libre de Bruxelles, B-1070 Brussels, Belgium

2 Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, B-1070 Brussels, Belgium

For all author emails, please log on.

Critical Care 2012, 16:186  doi:10.1186/cc11837


See related research by Heringlake et al., http://ccforum.com/content/16/4/R156

The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/16/6/186


Published:12 December 2012

© 2012 BioMed Central Ltd

Abstract

The rationale of urine alkalinization through intravenous sodium bicarbonate to prevent cardiac surgery-associated acute kidney injury relies on several pathophysiological arguments. Urine alkalinization is easily feasible in the ICU setting and is often considered to be associated with few side effects. In a previous issue of Critical Care, a retrospective study evaluates the effect of routine intravenous bicarbonate use to prevent cardiac surgery-associated acute kidney injury with cardiopulmonary bypass. This commentary discusses recent data on the use of bicarbonate to prevent cardiac surgery-associated acute kidney injury.

Commentary

In a previous issue of Critical Care, Heringlake and colleagues [1] report important results of a cohort analysis of use of bicarbonate to prevent cardiac surgery-associated acute kidney injury (CSA-AKI). Acute kidney injury (AKI) is common in hospitalized patients and is associated with increased morbidity and mortality. Cardiac surgery with cardiopulmonary bypass (CPB) is the second leading cause of AKI in the ICU, just after sepsis [2]. CSA-AKI incidence varies widely in the literature, usually in between 3% and 50% of patients undergoing CPB [3,4]. Its occurrence depends on several procedure-related (type of cardiac surgery, duration of aortic cross-clamping, CPB time) and patient-dependent factors (age, chronic kidney disease, low left ventricular ejection fraction, peripheral vascular disease, diabetes). The incidence of CSA-AKI is only 2.3% in isolated coronary artery bypass graft procedures in patients without comorbidities but its incidence rises up to 15% in patients also with chronic kidney disease [5]. Due to its significant incidence and influence on resource utilization and potentially on mortality, the prevention and/or treatment of CSA-AKI is a relevant issue.

Pathophysiology of CPB-AKI is complex, mainly relying on hemodynamic and inflammatory disturbances [3,6]. CPB is associated with ischemia-reperfusion injury but also with significant release of free hemoglobin and iron. Nevertheless, the respective importance of the different pathophysiological processes in CSA-AKI remains unclear. In addition, nephrotoxic drugs, anemia and blood transfusions may further exacerbate CSA-AKI.

Experimental data have shown that higher tubular pH could be protective in the presence of hemoglobinuria or myoglobinuria [7], especially through inhibition of hydroxyl radical generation and lipid peroxidation, which could be central in AKI [8-10]. In analogy with the beneficial effects of urine alkalinization after rhabdomyolysis [11], urine alkalinization after intravenous bicarbonate was thought to prevent CSA-AKI. In a pilot randomized study including 100 patients submitted to cardiac surgery with CPB, perioperative bicarbonate administration decreased the proportion of patients experiencing an increase in creatinine from 52 to 32% (P = 0.043) [12]. In addition, bicarbonate blunted the increase in biomarkers of AKI.

However, bicarbonate may not be the right agent to prevent CSA-AKI. Indeed, bicarbonate failed to prevent experimental ischemia-induced AKI [13]. It also fails to prevent contrast-induced nephropathy [14,15], another condition where ischemia is thought to occur. Hence, confirmatory trials in CSA-AKI are warranted.

In this issue, Heringlake and colleagues [1] reported the absence of superiority of intravenous bicarbonate for the prevention of CSA-AKI in comparison to saline. The authors retrospectively compared a cohort of 280 patients who received 4 mmol sodium bicarbonate per kilogram to a control cohort. The proportion of patients experiencing an increase in creatinine by 25% was similar in both groups (41.1% in bicarbonate versus 32.9% in control, P = not significant). Strikingly, this study is in contrast to the pilot study by Haase and colleagues [12], even though intravenous bicarbonate was used in a comparable manner and similarly alkalinized blood pH in both studies.

Several factors could explain the differences between these two studies. First, the Haase study included prospectively selected patients with significant risk for CSA-AKI while the Heringlake study was retrospective and included nearly all patients undergoing cardiacsurgery with CPB in their center. As mentioned above, heterogeneity in patient populations is an important factor determining the risk for CSA-AKI. This may be explained by inclusion in the latter trial of 38% of patients undergoing isolated coronary artery bypass graft, which shows the lowest CSA-AKI risk. This limits of course the chances to see a beneficial impact of bicarbonate. Nevertheless the incidence of CSA-AKI was still close to 33%, which is not negligible. Second, the Heringlake trial had the advantage of including almost all patients admitted to their center, which increases external validity of the results. Interestingly, bicarbonate may also be associated with detrimental effects. Mean arterial blood pressure was lower after induction of anesthesia, and patients required more fluids and vasopressors and spent more time in a high dependency unit [1]. Previous work has already drawn attention to the side effects of bicarbonate: overcorrection of acidosis significantly increased mortality [16] and several experiments have reported that intracellular alkalinization hastened cell death after anoxia, stimulated superoxide formation, enhanced pro-inflammatory cytokine release and apoptosis, and increased blood lactate and ketone bodies [17]. Therefore, use of bicarbonate for CSA-AKI prevention could be a double-edged sword where risk may overwhelm benefits if applied in a non-selected patient population.

These contradictory data raise questions about bicarbonate efficiency for CSA-AKI prevention. From the data published, it seems that bicarbonate is useless in an unselected population [1]. Bicarbonate may still be effective in patients at high risk of CSA-AKI and results of confirmatory trials are needed. Nevertheless, preliminary results of a randomized trial in 427 patients at high risk of CSA-AKI reported a similar incidence of CSA-AKI of 45% in the bicarbonate group and 44% in the saline group [18]. The debate is therefore still open but data do not actually support routine use of bicarbonate for CSA-AKI prevention.

Abbreviations

AKI: acute kidney injury; CPB: cardiopulmonary bypass; CSA-AKI: cardiac surgery-associated acute kidney injury.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

The authors equally contributed to this work.

References

  1. Heringlake M, Heinze H, Schubert M, Novak Y, Guder J, Kleinebrahm M, Paarmann H, Hanke T, Schon J: A perioperative infusion of sodium bicarbonate does not improve renal function in cardiac surgery patients: a prospective observational cohort study.

    Crit Care 2012, 16:R156. PubMed Abstract | BioMed Central Full Text OpenURL

  2. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C: Acute renal failure in critically ill patients: a multinational, multicenter study.

    JAMA 2005, 294:813-818. PubMed Abstract | Publisher Full Text OpenURL

  3. Haase M, Bellomo R, Haase-Fielitz A: Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury.

    J Am Coll Cardiol 2010, 55:2024-2033. PubMed Abstract | Publisher Full Text OpenURL

  4. Weisberg LS: Sodium bicarbonate for renal protection after heart surgery: let's wait and see.

    Crit Care Med 2009, 37:333-334. PubMed Abstract | Publisher Full Text OpenURL

  5. Shahian DM, O'Brien SM, Filardo G, Ferraris VA, Haan CK, Rich JB, Normand SL, DeLong ER, Shewan CM, Dokholyan RS, Peterson ED, Edwards FH, Anderson RP: The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 1 - coronary artery bypass grafting surgery.

    Ann Thorac Surg 2009, 88:S2-22. PubMed Abstract | Publisher Full Text OpenURL

  6. Haase M, Haase-Fielitz A, Bellomo R: Cardiopulmonary bypass, hemolysis, free iron, acute kidney injury and the impact of bicarbonate.

    Contrib Nephrol 2010, 165:28-32. PubMed Abstract | Publisher Full Text OpenURL

  7. Atkins JL: Effect of sodium bicarbonate preloading on ischemic renal failure.

    Nephron 1986, 44:70-74. PubMed Abstract | Publisher Full Text OpenURL

  8. Caulfield JL, Singh SP, Wishnok JS, Deen WM, Tannenbaum SR: Bicarbonate inhibits N-nitrosation in oxygenated nitric oxide solutions.

    J Biol Chem 1996, 271:25859-25863. PubMed Abstract | Publisher Full Text OpenURL

  9. Hingorani S, Molitoris BA, Himmelfarb J: Ironing out the pathogenesis of acute kidney injury.

    Am J Kidney Dis 2009, 53:569-571. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  10. Bonventre JV, Weinberg JM: Recent advances in the pathophysiology of ischemic acute renal failure.

    J Am Soc Nephrol 2003, 14:2199-2210. PubMed Abstract | Publisher Full Text OpenURL

  11. Bosch X, Poch E, Grau JM: Rhabdomyolysis and acute kidney injury.

    N Engl J Med 2009, 361:62-72. PubMed Abstract | Publisher Full Text OpenURL

  12. Haase M, Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Reade MC, Bagshaw SM, Seevanayagam N, Seevanayagam S, Doolan L, Buxton B, Dragun D: Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: a pilot double-blind, randomized controlled trial.

    Crit Care Med 2009, 37:39-47. PubMed Abstract | Publisher Full Text OpenURL

  13. Sporer H, Lang F, Oberleithner H, Greger R, Deetjen P: Inefficacy of bicarbonate infusions on the course of postischaemic acute renal failure in the rat.

    Eur J Clin Invest 1981, 11:311-315. PubMed Abstract | Publisher Full Text OpenURL

  14. Baber U, Mehran R: Prevention of contrast-induced AKI - the ongoing saga.

    Nat Rev Nephrol 2012, 8:260-261. PubMed Abstract | Publisher Full Text OpenURL

  15. Zoungas S, Ninomiya T, Huxley R, Cass A, Jardine M, Gallagher M, Patel A, Vasheghani-Farahani A, Sadigh G, Perkovic V: Systematic review: sodium bicarbonate treatment regimens for the prevention of contrast-induced nephropathy.

    Ann Intern Med 2009, 151:631-638. PubMed Abstract | Publisher Full Text OpenURL

  16. Anderson LE, Henrich WL: Alkalemia-associated morbidity and mortality in medical and surgical patients.

    South Med J 1987, 80:729-733. PubMed Abstract | Publisher Full Text OpenURL

  17. Sabatini S, Kurtzman NA: Bicarbonate therapy in severe metabolic acidosis.

    J Am Soc Nephrol 2009, 20:692-695. PubMed Abstract | Publisher Full Text OpenURL

  18. McGuinness P, Parke RL, Bellomo R, van Haren FM: Sodium bicarbonate to reduce cardiac surgery associated acute kidney injury: A phase II multicentre, double-blind, randomized clinical trial [abstract].

    Am J Respir Crit Care Med 2012, 185:A6857. OpenURL