Advertisement

Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial

Published:November 21, 2014DOI:https://doi.org/10.1016/j.jhep.2014.11.017

      Background & Aims

      Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial.

      Methods

      A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1 g/kg on day 3; albumin group [ALB]: n = 96) or antibiotics alone (control group [CG]: n = 97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate.

      Results

      Forty-seven (24.6%) patients died (ALB: n = 27 vs. CG: n = 20; 3-month survival: 70.2% vs. 78.3%; p = 0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p = 0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p = 0.88). By multivariate analysis, MELD score (p <0.0001), pneumonia (p = 0.0041), hyponatremia (p = 0.031) and occurrence of renal failure (p <0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion.

      Conclusions

      In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

      Abbreviations:

      AKI (acute kidney injury), IQR (interquartile range), LVP (large-volume paracentesis), MDRD (modification of diet in renal disease), SBP (spontaneous bacterial peritonitis), SIRS (systemic inflammatory response syndrome)

      Keywords

      Linked Article

      • Reply to “Albumin infusion in cirrhotic patients with non-SBP infections: End of the story?”
        Journal of HepatologyVol. 63Issue 3
        • Preview
          We greatly appreciate the comments by Lucidi et al. [1]. Firstly, we acknowledge that, despite well-conducted randomization to reduce the risk of selection bias at trial entry [2], the presence of ascites was more frequently reported in the albumin (ALB) group as compared with the control group (75.8 vs. 59.6; p = 0.017). We have to remember that using an alpha risk of 5%, the probability of there being no imbalance between groups for any one baseline characteristic is 0.95. Assuming the characteristics are independent, there is a non-negligible 1 − (0.95)n probability of observing a significant imbalance between groups when comparing n baseline characteristics. 
        • Full-Text
        • PDF
        Open Access
      • Albumin infusion in cirrhotic patients with infections other than spontaneous bacterial peritonitis: End of the story?
        Journal of HepatologyVol. 63Issue 3
        • Preview
          We read with interest the recent manuscript by Thevenot et al. [1] which adds data to the debate on the potential beneficial effect of albumin administration during episodes of infections other than spontaneous bacterial peritonitis (SBP) in cirrhotic patients [2–4].
        • Full-Text
        • PDF
        Open Access
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Fernandez J.
        • Navasa M.
        • Gomez J.
        • Colmenero J.
        • Vila J.
        • Arroyo V.
        • et al.
        Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis.
        Hepatology. 2002; 35: 140-148
        • Arvaniti V.
        • D’Amico G.
        • Fede G.
        • Manousou P.
        • Tsochatzis E.
        • Pleguezuelo M.
        • et al.
        Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis.
        Gastroenterology. 2010; 139: 1246-1256
        • Wong F.
        • Bernardi M.
        • Balk R.
        • Christman B.
        • Moreau R.
        • Garcia-Tsao G.
        • et al.
        Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.
        Gut. 2005; 54: 718-725
        • Wiest R.
        • Krag A.
        • Gerbes A.
        Spontaneous bacterial peritonitis: recent guidelines and beyond.
        Gut. 2012; 61: 297-310
        • Follo A.
        • Llovet J.M.
        • Navasa M.
        • Planas R.
        • Forns X.
        • Francitorra A.
        • et al.
        Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis.
        Hepatology. 1994; 20: 1495-1501
        • Sort P.
        • Navasa M.
        • Arroyo V.
        • Aldeguer X.
        • Planas R.
        • Ruiz-del-Arbol L.
        • et al.
        Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.
        N Engl J Med. 1999; 341: 403-409
        • Tandon P.
        • Garcia-Tsao G.
        Renal dysfunction is the most important independent predictor of mortality in cirrhotic patients with spontaneous bacterial peritonitis.
        Clin Gastroenterol Hepatol. 2011; 9: 260-265
        • Fasolato S.
        • Angeli P.
        • Dallagnese L.
        • Maresio G.
        • Zola E.
        • Mazza E.
        • et al.
        Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features.
        Hepatology. 2007; 45: 223-229
        • Terra C.
        • Guevara M.
        • Torre A.
        • Gilabert R.
        • Fernández J.
        • Martín-Llahí M.
        • et al.
        Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score.
        Gastroenterology. 2005; 129: 1944-1953
        • Pereira G.
        • Guevara M.
        • Fagundes C.
        • Solá E.
        • Rodríguez E.
        • Fernández J.
        • et al.
        Renal failure and hyponatremia in patients with cirrhosis and skin and soft tissue infection. A retrospective study.
        J Hepatol. 2012; 56: 1040-1046
        • Ruiz-del-Arbol L.
        • Urman J.
        • Fernandez J.
        • González M.
        • Navasa M.
        • Monescillo A.
        • et al.
        Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis.
        Hepatology. 2003; 38: 1210-1218
        • Bortoluzzi A.
        • Ceolotto G.
        • Gola E.
        • Sticca A.
        • Bova S.
        • Morando F.
        • et al.
        Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites: molecular mechanisms.
        Hepatology. 2013; 57: 266-276
        • Fernandez J.
        • Navasa M.
        • Garcia-Pagan J.C.
        • G-Abraldes J.
        • Jiménez W.
        • Bosch J.
        • et al.
        Effect of intravenous albumin on systemic and hepatic hemodynamics and vasoactive neurohormonal systems in patients with cirrhosis and spontaneous bacterial peritonitis.
        J Hepatol. 2004; 41: 384-390
        • Garcia-Martinez R.
        • Caraceni P.
        • Bernardi M.
        • Gines P.
        • Arroyo V.
        • Jalan R.
        Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications.
        Hepatology. 2013; 58: 1836-1846
        • Salerno F.
        • Navickis R.J.
        • Wilkes M.M.
        Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials.
        Clin Gastroenterol Hepatol. 2013; 11: e1
        • Runyon B.A.
        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: 1651-1653
      1. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis.
        J Hepatol. 2010; 53: 397-417
        • Guevara M.
        • Terra C.
        • Nazar A.
        • Solà E.
        • Fernández J.
        • Pavesi M.
        • et al.
        Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study.
        J Hepatol. 2012; 57: 759-765
        • Bone R.C.
        • Balk R.A.
        • Cerra F.B.
        • Dellinger R.P.
        • Fein A.M.
        • Knaus W.A.
        • et al.
        Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.
        Chest. 1992; 101: 1644-1655
        • Cardenas A.
        • Gines P.
        Management of complications of cirrhosis in patients awaiting liver transplantation.
        J Hepatol. 2005; 42: S124-S133
        • Levey A.S.
        • Coresh J.
        • Greene T.
        • Stevens L.A.
        • Zhang Y.L.
        • Hendriksen S.
        • et al.
        Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.
        Ann Intern Med. 2006; 145: 247-254
        • Borzio M.
        • Salerno F.
        • Piantoni L.
        • Cazzaniga M.
        • Angeli P.
        • Bissoli F.
        • et al.
        Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study.
        Dig Liver Dis. 2001; 33: 41-48
        • Rosa H.
        • Silverio A.O.
        • Perini R.F.
        • Perini R.F.
        • Arruda C.B.
        Bacterial infection in cirrhotic patients and its relationship with alcohol.
        Am J Gastroenterol. 2000; 95: 1290-1293
        • Caly W.R.
        • Strauss E.
        A prospective study of bacterial infections in patients with cirrhosis.
        J Hepatol. 1993; 18: 353-358
        • Gines A.
        • Fernandez-Esparrach G.
        • Monescillo A.
        • Vila C.
        • Domènech E.
        • Abecasis R.
        • et al.
        Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis.
        Gastroenterology. 1996; 111: 1002-1010
        • Martin-Llahi M.
        • Pepin M.N.
        • Guevara M.
        • Díaz F.
        • Torre A.
        • Monescillo A.
        • et al.
        Terlipressin and albumin vs. albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study.
        Gastroenterology. 2008; 134: 1352-1359
        • Navasa M.
        • Follo A.
        • Filella X.
        • Jiménez W.
        • Francitorra A.
        • Planas R.
        • et al.
        Tumor necrosis factor and interleukin-6 in spontaneous bacterial peritonitis in cirrhosis: relationship with the development of renal impairment and mortality.
        Hepatology. 1998; 27: 1227-1232
        • Belcher J.M.
        • Garcia-Tsao G.
        • Sanyal A.J.
        • Bhogal H.
        • Lim J.K.
        • Ansari N.
        • et al.
        Association of AKI with mortality and complications in hospitalized patients with cirrhosis.
        Hepatology. 2013; 57: 753-762
        • Tsien C.D.
        • Rabie R.
        • Wong F.
        Acute kidney injury in decompensated cirrhosis.
        Gut. 2013; 62: 131-137
        • Fagundes C.
        • Barreto R.
        • Guevara M.
        • Garcia E.
        • Solà E.
        • Rodríguez E.
        • et al.
        A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis.
        J Hepatol. 2013; 59: 474-481
        • Wong F.
        • O’Leary J.G.
        • Reddy K.R.
        • Patton H.
        • Kamath P.S.
        • Fallon M.B.
        • et al.
        North American Consortium for the Study of End-Stage Liver Disease. New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection.
        Gastroenterology. 2013; 145: 1280-1288
        • Nazar A.
        • Guevara M.
        • Sitges M.
        • Terra C.
        • Solà E.
        • Guigou C.
        • et al.
        LEFT ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction.
        J Hepatol. 2013; 58: 51-57
        • Caramelo C.
        • Fernandez-Munoz D.
        • Santos J.C.
        • Blanchart A.
        • Rodriguez-Puyol D.
        • López-Novoa J.M.
        • et al.
        Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats.
        Hepatology. 1986; 6: 129-134
        • Ellman H.
        Capillary permeability in septic patients.
        Crit Care Med. 1984; 12: 629-633
        • Ribera J.
        • Pauta M.
        • Melgar-Lesmes P.
        • Tugues S.
        • Fernández-Varo G.
        • Held K.F.
        • et al.
        Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats.
        Gut. 2013; 62: 138-145
        • Kumar R.
        • Kumar S.
        • Lata S.
        Albumin infusion may deleteriously promote extracellular fluid overload without improving circulating hypovolemia in patients of advanced cirrhosis with diabetes mellitus and sepsis.
        Med Hypotheses. 2013; 80: 452-455
        • Kim W.R.
        • Biggins S.W.
        • Kremers W.K.
        • Wiesner R.H.
        • Kamath P.S.
        • Benson J.T.
        • et al.
        Hyponatremia and mortality among patients on the liver-transplant waiting list.
        N Engl J Med. 2008; 359: 1018-1026