Subjects

Abstract

Objectives

Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia.

Methods

Hospitalized cirrhotic patients included in the NACSELD (North American Consortium for End-Stage Liver Disease) cohort with hyponatremia (Na <130mmol/L) were divided into those receiving intravenous albumin or not. Determinants of hyponatremia resolution (Na ≥135 meq/L) and 30-day survival were analyzed using regression and ANCOVA models.

Results

Overall, 2435 patients, of whom 1126 had admission hyponatremia, were included. Of these, 777 received 225 (IQR 100,400) g of albumin, while 349 did not. Patients given albumin had a higher admission MELD score, and serum creatinine and lower admission Na and mean arterial pressure (MAP). However they experienced a higher maximum Na and hyponatremia resolution (69% vs 61%, p = 0.008) compared to those who did not. On regression, delta Na was independently associated with admission creatinine, MAP and albumin use. On ANCOVA with logistic regression, there was a significant difference in hyponatremia resolution between those who did or did not receive albumin, even after adjustment for admission Na and GFR (85.41% vs 44.78%, p = 0.0057, OR: 1.50 95% CI: 1.13–2.00). Independent predictors of 30-day survival were hyponatremia resolution, age, ACLF, and admission GFR.

Conclusion

Hospitalized patients with cirrhosis and hyponatremia who received intravenous albumin had a higher rate of hyponatremia resolution independent of renal function and baseline sodium levels, which was in turn associated with a better 30-day survival.

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References

  1. 1.

    Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med. 2008;359:1018–26.

  2. 2.

    Cardenas A, Sola E, Rodriguez E, et al. Hyponatremia influences the outcome of patients with acute-on-chronic liver failure: an analysis of the CANONIC study. Crit Care. 2014;18:700.

  3. 3.

    Biggins SW, Kim WR, Terrault NA, et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. 2006;130:1652–60.

  4. 4.

    Biggins SW, Rodriguez HJ, Bacchetti P, et al. Serum sodium predicts mortality in patients listed for liver transplantation. Hepatology. 2005;41:32–9.

  5. 5.

    Biggins SW. Use of serum sodium for liver transplant graft allocation: A decade in the making, now is it ready for primetime? Liver Transpl. 2015;21:279–81.

  6. 6.

    Sigal SH. Hyponatremia in cirrhosis. J Hosp Med. 2012;7(Suppl 4):S14–7.

  7. 7.

    Lizaola B, Bonder A, Tapper EB, et al. The changing role of sodium management in cirrhosis. Curr Treat Options Gastroenterol. 2016;14:274–84.

  8. 8.

    Gaglio P, Marfo K, Chiodo J 3rd. Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V(2)-receptor antagonist tolvaptan. Dig Dis Sci. 2012;57:2774–85.

  9. 9.

    Ahluwalia V, Heuman DM, Feldman G, et al. Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis. J Hepatol. 2015;62:75–82.

  10. 10.

    Dahl E, Gluud LL, Kimer N, et al. Meta-analysis: the safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatraemia. Aliment Pharmacol Ther. 2012;36:619–26.

  11. 11.

    McCormick PA, Mistry P, Kaye G, et al. Intravenous albumin infusion is an effective therapy for hyponatraemia in cirrhotic patients with ascites. Gut. 1990;31:204–7.

  12. 12.

    Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology. 2014;60:250–6.

  13. 13.

    O’Leary JG, Reddy KR, Garcia-Tsao G, et al. NACSELD Acute-on-Chronic Liver Failure (NACSELD-ACLF) Score predicts 30-day survival in hospitalized patients with cirrhosis. Hepatology. 2018; https://doi.org/10.1002/hep.29773

  14. 14.

    Angeli P, Wong F, Watson H, et al. Hyponatremia in cirrhosis: results of a patient population survey. Hepatology. 2006;44:1535–42.

  15. 15.

    Ahluwalia V, Heuman DM, Feldman G, et al. Correction of hyponatremia Improves cognition, quality of life, and brain edema in cirrhosis. J Hepatol. 2015;62: 75–82.

  16. 16.

    Wong F, Blei AT, Blendis LM, et al. A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter, randomized, placebo-controlled trial. Hepatology. 2003;37:182–91.

  17. 17.

    Ahluwalia V, Wade JB, Thacker L, et al. Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis. J Hepatol. 2013;59:467–73.

  18. 18.

    European Association for the Study of the L. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417.

  19. 19.

    Runyon BA, Aasld. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology 2013;57:1651–3.

  20. 20.

    Arroyo V, Garcia-Martinez R, Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol. 2014;61:396–407.

  21. 21.

    O’Brien AJ, Fullerton JN, Massey KA, et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med. 2014;20:518–23.

  22. 22.

    Arroyo V. Review article: albumin in the treatment of liver diseases–new features of a classical treatment. Aliment Pharmacol Ther. 2002;16(Suppl 5):1–5.

  23. 23.

    Garcia-Martinez R, Caraceni P, Bernardi M, et al. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology. 2013;58:1836–46.

  24. 24.

    Nguyen MK, Ornekian V, Kao L, et al. Defining the role of albumin infusion in cirrhosis-associated hyponatremia. Am J Physiol Gastrointest Liver Physiol. 2014;307:G229–32.

  25. 25.

    Garioud A, Cadranel JF, Pauwels A, et al. Albumin use in patients with cirrhosis in France: results of the “ALBU-LIVE” Survey: a case for better EASL guidelines diffusion and/or revision. J Clin Gastroenterol. 2017;51:831–8.

  26. 26.

    Bajaj JS, O’Leary JG, Wong F, et al. Variations in albumin use in patients with cirrhosis: an AASLD members survey. Hepatology. 2015;62:1923–4.

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Affiliations

  1. Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA

    • Jasmohan S. Bajaj MD
    •  & Leroy R. Thacker PhD
  2. University of Alberta, Edmonton, AB, Canada

    • Puneeta Tandon MD
  3. Dallas VA Medical Center and Baylor University Medical Center, Dallas, TX, USA

    • Jacqueline G. O’Leary MD
  4. University of Washington, Seattle, WA, USA

    • Scott W. Biggins MD
  5. University of Denver, Colorado, CO, USA

    • Scott W. Biggins MD
  6. University of Toronto, Toronto, ON, Canada

    • Florence Wong MD
  7. Mayo Clinic, Rochester, MN, USA

    • Patrick S. Kamath MD
  8. Yale University Medical Center, West Haven, CT, USA

    • Guadalupe Garcia-Tsao MD
  9. University of Tennessee, Memphis, TN, USA

    • Benedict Maliakkal MD
  10. University of Rochester, Rochester, NY, USA

    • Benedict Maliakkal MD
  11. University of California, San Francisco, CA, USA

    • Jennifer C. Lai MD
  12. University of Arizona, Phoenix, AZ, USA

    • Michael Fallon MD
  13. University of Texas, Houston, TX, USA

    • Michael Fallon MD
  14. Mercy Medical Center, Baltimore, MD, USA

    • Paul Thuluvath MD
  15. Mayo Clinic, Scottsdale, AZ, USA

    • Hugo E. Vargas MD
  16. Emory University Medical Center, Atlanta, GA, USA

    • Ram M. Subramanian MD
  17. University of Pennsylvania, Philadelphia, PA, USA

    • K. Rajender Reddy MD

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Guarantor of the article

JSB is the guarantor of the article.

Specific author contributions

All authors enrolled patients and were responsible for drafting and editing the manuscript. LRT was involved in the statistical analysis.

Financial Support

The NACSELD registry was supported by an investigator-initiated grant from Grifols Pharmaceuticals.

Potential competing interests

JSB, FW, GGT, SWB, JO, KRR, and PT are consultants for Grifols Pharmaceuticals. The remaining authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Jasmohan S. Bajaj MD.

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DOI

https://doi.org/10.1038/s41395-018-0119-3