Year : 2007 | Volume
: 13 | Issue : 4 | Page : 204--206
Albumin use in cirrhotic patients: The case against
Muhammad R Syed, Khalid I Bzeizi
Division of Hepatology, Department of Medicine, Riyadh Military Hospital, Riyadh, Saudi Arabia
Khalid I Bzeizi
Department of Medicine, Riyadh Military Hospital, P. O. Box 7897, Riyadh - 11159
|How to cite this article:|
Syed MR, Bzeizi KI. Albumin use in cirrhotic patients: The case against.Saudi J Gastroenterol 2007;13:204-206
|How to cite this URL:|
Syed MR, Bzeizi KI. Albumin use in cirrhotic patients: The case against. Saudi J Gastroenterol [serial online] 2007 [cited 2021 Jan 20 ];13:204-206
Available from: https://www.saudijgastro.com/text.asp?2007/13/4/204/36756
Albumin was used in patients with cirrhosis as early as 1946.  It is administered to cirrhotic patients undergoing large-volume paracentesis for the prevention of renal impairment in spontaneous bacterial peritonitis and more recently in the treatment of hepatorenal syndrome. The current practice has shifted into the exclusive use of albumin in the abovementioned conditions, and eyebrows would be raised if alternative plasma expanders were used instead. Have we got the solid evidence behind albumin to justify its current prominence? Should we be more careful with risks involved using albumin, such as the theoretical possibility of transmission of known and unknown diseases, including viral and prion related diseases? How about the cost? In one of the studies, it was determined that the cost of plasma expansion with albumin following paracentesis was approximately 370 US dollars (USD). The cost of Dextran for treating similar patients was 15 USD.  In a large part of the world, such cost is generally unaffordable and for the rest, it remains sufficiently expensive to justify the reassessment of its use in such patients. Further, a systematic review by Cochrane Injuries Group Albumin Reviewers  concluded that albumin administration does not reduce mortality in critically ill patients with hypovolaemia, burns or hypoalbuminemia and a strong suggestion was put forward that it may in fact increase mortality.
Perhaps it is the time to look back and evaluate the evidence. In the earlier article, Drs. Sanai and Marotta have assessed the evidence for albumin and concluded that we should use this product with no reservation for the abovementioned conditions. In this article, we intend to take the opposite stand and provide the evidence that albumin need not be our immediate out-of-shelf product for use in patients with the abovementioned complications of cirrhosis.
Plasma Expansion in Paracentesis
The prevention of paracentesis-induced circulatory dysfunction became a reason for albumin administration. Currently, paracentesis is widely used in the treatment of ascites as it has been found to be more effective than diuretics.  Total paracentesis is also preferred over multiple large-volume paracentesis as it is associated with lower rates of local complications.  When cirrhotic patients with tense ascites are treated with therapeutic paracentesis without plasma expansion, up to 70% develop the impairment of circulatory function.  This impairment is defined by a significant increase in the plasma renin activity. The risk of developing circulatory dysfunction is 20% when less than 5 L of ascitic fluid is removed. , The risk for this amount of fluid remains the same even if the plasma expansion is used or not. The findings of this study suggest that one can safely remove 5 L or less amount of ascitic fluid from a patient with ascites without the risk of developing circulatory dysfunction.
Planas et al .  investigated whether albumin can be substituted by less expensive plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis. Eighty-eight patients (16 with renal failure) who underwent paracentesis were randomly assigned to receive IV albumin (43 patients) or Dextran 70. Both substances were administered at a dose of 8 g/L of the removed ascitic fluid. Patients were discharged from the hospital with diuretics, and cases developing tense ascites during the follow-up were treated according to their initial schedule. Total paracentesis was effective in eliminating the ascites in all, but two cases in each group. Neither paracentesis with IV albumin infusion nor paracentesis with IV Dextran-70 infusion was associated with significant changes in renal and hepatic function or serum electrolytes. The incidence of renal impairment (one case in each group), hyponatremia (three and four cases, respectively) and other complications (hepatic encephalopathy, gastrointestinal hemorrhage and bacterial infections) after paracentesis and the clinical course of the disease as estimated by the probability of readmission to hospital during follow-up, causes of readmission, probability of survival and causes of death were similar in the two groups of patients. The impact of paracentesis on effective intravascular volume was assessed by measuring the surrogate markers (plasma renin activity and aldosterone concentration) before and 2 and 6 days of treatment. In patients treated with albumin, no significant changes were observed in renin and aldosterone during the entire period of observation. In contrast, both the parameters significantly increased on the sixth day of treatment in patients receiving Dextran 70. A significant increase in plasma renin activity and aldosterone concentration (30% over baseline values) was observed in 51% of patients treated with Dextran 70 and in only 15% of those treated with albumin (χ2 = 10.4; P = 0.0012). These results indicate that although Dextran 70 is less efficacious than albumin in protecting cirrhotic patients treated with total paracentesis from the decrease in the effective intravascular volume, it appears to be capable of preventing the renal and electrolyte complications induced by this therapeutic procedure.
In another study by Fassio et al .  41 patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 L associated with Dextran 70 as the volume expander (6 g for each 1000 ml of ascites removed) or paracentesis with albumin (6 g for each 1000 ml of ascites). No significant changes were observed in the liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. The probability of survival and readmission to the hospital because of tense ascites were similar in both the groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient under treatment. The results of these studies indicate that repeated large-volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. With its reduced cost and safety profile, Dextran 70 may be considered as the acceptable first-line choice for cirrhotics undergoing paracentesis for tense ascites.
Spontaneous Bacterial Peritonitis (SBP)
The evidence for the benefit of albumin in SBP is derived from a sole study done in 1999. Sort et al .  randomized 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). They concluded that addition of albumin to antibiotics for treatment of SBP reduces the incidence of renal impairment and improves survival.
The results obtained in this study may have been merely due to the plasma-expanding properties of albumin. The study had the limitation of depriving the patients in the control arm from any form of plasma expansion. Therefore, a comparative study with another plasma expander such as Dextran or polygeline is warranted before determining the true place of albumin in the management protocols of SBP.
Further, in the same study, only patients with serum bilirubin > 68.4 Ámol/L, blood urea nitrogen (BUN) > 30 mg/dl or serum creatinine > 88.4 Ámol/L appeared to benefit from albumin. The authors, in fact, stated that the incidence of renal impairment among patients with a serum bilirubin level of less than 4 mg/dl and a serum creatinine level of less than 1 mg/dl was very low in both treatment groups (7 percent and 0 percent in the cefotaxime and cefotaxime plus albumin groups, respectively).
The support for the theory that albumin with antibiotics may benefit only a subgroup of patients with higher bilirubin levels comes from another recent article by Stanca et al .  This article describes a therapeutic protocol involving 38 episodes of SBP to assess whether albumin is required in all cases of SBP. Patients were divided into two groups, one was a low risk group with bilirubin levels lower than 68.4 Ámol/L and the other was a high risk group with bilirubin levels greater than 68.4 Ámol/L. The diagnosis and treatment of SBP were based on established guidelines, but only the high risk group received albumin. The results showed that in the low risk group (15 patients, 18 episodes), SBP resolved in all of them and none developed renal impairment. None of the 15 patients in this group died. In the high-risk group (21 patients, 26 episodes), renal impairment was present in 12 patients (57%) and 15 episodes (58%). The outcome in five (24%) patients (19% episodes) was death.
The results of the two studies suggest that albumin may only be beneficial in the treatment of SBP in a subgroup of patients who have higher levels of bilirubin (> 68.4 Ámol/L) and has negligible benefits in SBP patients with normal bilirubin. This further strengthens our argument that there is no solid evidence to prescribe albumin indiscriminately in all cases of SBP.
Hepatorenal syndrome (HRS) is one of the dreaded complications of liver cirrhosis. It is a diagnosis of exclusion and is thought to develop as a renal response to splanchnic vasodilation in cirrhotics. The renal regulatory mechanisms sense the reduced perfusion and vasoconstrict. This vasoconstriction is the pathognomonic hallmark of HRS.  Recently, progress has been made with the use of vasoconstictors such as terlipressin in the treatment of such patients as a bridge to liver transplantation. , The supporters of albumin will cite studies in which albumin plus terlipressin in patients with type 1 HRS had a favorable response.  However, one of the largest retrospective studies to look at the benefits of terlipressin in patients with type 1 HRS  shows that in patients with type-1 HRS, terlipressin-induced improved renal function is associated with an increase in survival of such patients irrespective of whether they received albumin or not. This study considered 99 patients with type-1 HRS in 24 different centers. To date, this is the largest study of its kind, and with no meta-analysis, the findings of the above study carry significant weight in the debate on the role of albumin for the management of HRS. Further, we feel that more studies are required to study the effects of other plasma expanders in place of albumin before attributing any benefits directly to albumin.
There is strong evidence that paracentesis up to 5 L does not warrant plasma expansion. Albumin may have the edge over Dextran 70 in patients requiring large volume paracentesis in whom there is an element of renal impairment. There is no evidence for any survival benefit in patients who received albumin as compared to those given Dextran 70. The renal benefit that has been advocated as the main advantage medium term does not translate into a survival or quality of life benefit in this group of patients sufficiently to justify the cost.
The benefit of terlipressin has been effectively demonstrated in clinical trials for the management of HRS. That is not the case with albumin. Trials were done in conjunction with vasconstrictors. Further, no head-to-head comparisons with equivalent plasma expanders were used in this context.
Further studies are required to verify the benefit of albumin in SBP. The only study that strongly recommended its use in this condition was not a randomized trial that compared albumin with Dextran 70, the cheaper and equivalent product for plasma expansion. Further, the patients in the control group did not receive any kind of volume replacement matching albumin supplement . Given the paucity of studies performed thus far, it appears that more work is required before determining the proper place for albumin in the management of SBP. At this stage, if to give the benefit of the doubt until further studies are published, we propose restricting its use in SBP patients, particularly those with concomitant renal impairment.
|1||Kunkel HG, Labby DH, Ahrens EH, Shank RE, Hoagland CL. The use of concentrated human serum albumin in the treatment of cirrhosis of the liver. J Clin Invest 1948;27:305-19.|
|2||Fassio E, Terq R, Landeira G, Abecasis R, Salemne M, Podesta A, et al . Paracentesis with Dextran 70 vs paracentesis with albumin in cirrhosis with tense ascites: Results of a randomized study. J Hepatol 1992;14:310-6.|
|3||Cochrane Injuries Group Albumin Reviewers. Human Albumin administration in critically ill patients: Systematic review of randomized controlled trials. BMJ 1998;317:235-40.|
|4||Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet 2003;362:1819-27.|
|5||Quintero E, Gines P, Arroyo V, Rimola A, Bory F, Planas R, et al . Paracentesis versus diuretics in the treatment of cirrhotics with tense ascites. Lancet 1985;1:611-2.|
|6||Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, et al . The management of ascites in cirrhosis: Report on the consensus conference of the International Ascites Club. Hepatology 2003;38:258-66.|
|7||Ginθs P, Titˇ L, Arroyo V, Planas R, Panιs J, Viver J, et al . Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gasteroenterolgy 1988;94:1493-502.|
|8||Ginθs A, Fernαndez-Esparrach G, Monescillo A, Vila C, Domθnech E, Abecasis R, et al . Randomized trial comparing albumin, dextran 70 and polygeline in cirrhotic patients with ascites treated by paracentesis. Gasteroenterolgy 1996;111:1002-10.|
|9||Sola-Vara J, Minana J, Ricart E, Planella M, Gonzαlez B, Torras X, et al . Randomized trial comparing albumin and saline in the prevention of paracentesis induced circulatory dysfunction in cirrhotic patients with ascites. Hepatology 2003;37:1147-53.|
|10||Planas R, Ginθs P, Arroyo V, Llach J, Panιs J, Vargas V, et al . Dextran-70 versus albumin as plasma expanders in cirrhotic patients with tense ascites treated with total paracentesis: Results of a randomized study. Gastroenterolgy 1990;99:1736-44.|
|11||Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, et al . Effect of plasma volume expansion on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-9.|
|12||Sigal SH, Stanca CM, Fernandez J, Arroyo V, Navasa M. Restricted use of Albumin for spontaneous bacterial peritonitis. Gut 2007;56:597-9.|
|13||Moreau R, Durand F, Poynard T, Duhamel C, Cervoni JP, Ichaο P, et al . Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: A retrospective multicenter study. Gastroenterology 2002;122:923-30.|
|14||Ortega R, Ginθs P, Uriz J, Cαrdenas A, Calahorra B, De Las Heras D, et al . Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: Results of a prospective, nonrandomized study. Hepatology 2002;36:941-8.|