Nutrition in Clinical Practice

http://ncp.sagepub.com/ Albumin Therapy in Clinical Practice

Christian M. Mendez, Craig J. McClain and Luis S. Marsano Nutr Clin Pract 2005 20: 314 DOI: 10.1177/0115426505020003314 The online version of this article can be found at: http://ncp.sagepub.com/content/20/3/314

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Invited Review
Albumin Therapy in Clinical Practice
Christian M. Mendez, MD; Craig J. McClain, MD; and Luis S. Marsano, MD
Department of Internal Medicine, University of Louisville Medical Center, Louisville, Kentucky ABSTRACT: Albumin is the predominant product of hepatic protein synthesis and one of the more abundant plasma proteins. Among its multiple physiologic roles, it plays an essential part in the generation of colloid-oncotic pressure. In the United States, the indications for which albumin therapy are considered include hypovolemia or shock, burns, hypoalbuminemia, surgery or trauma, cardiopulmonary bypass, acute respiratory distress syndrome, hemodialysis, and sequestration of protein-rich uids. The use of this relatively expensive therapy accounts for up to 30% of the total pharmacy budget in certain hospitals. The use of albumin therapy in different clinical situations and its inuence in morbidity and mortality have been reviewed in multiple randomized controlled trials and meta-analyses. Despite frequent reviews, the use of albumin remains controversial in several clinical situations. At the same time, these valuable reviews seem to have documented the advantages of albumin therapy in the management of ascites and claried the use of albumin in volume resuscitation. More studies have been recommended to investigate the use of albumin in different doses and its role in hypoalbuminemia. This article will provide an overview of albumin metabolism, use of albumin for volume expansion, the potential therapeutic role of albumin in liver disease, and the role of albumin therapy in nutrition.

Albumin infusions have been used for 50 years in the management of a diverse range of medical and surgical problems. Albumin infusions have multiple effects including volume expansion, an increase in colloid osmotic pressure, and hemodilution. This form of therapy is used in multiple clinical settings such as hypovolemia, shock, burns, surgery, trauma, cardiopulmonary bypass, acute respiratory distress syndrome, hemodialysis, acute liver failure, and

Correspondence: Christian M. Mendez, M.D., Department of Internal Medicine, University of Louisville Medical Center, 550 S. Jackson St., ACB 3rd Floor, Louisville, KY 40292. Electronic mail may be sent to cmmend01@gwise.louisville.edu.
0884-5336/05/2003-0314$03.00/0 Nutrition in Clinical Practice 20:314320, June 2005 Copyright 2005 American Society for Parenteral and Enteral Nutrition

ascites.1 The evidence to support albumin therapy in these diverse conditions is quite variable and a focus of this review. In this article, we will provide an overview of albumin metabolism, use of albumin for volume expansion, the potential therapeutic role of albumin in liver disease, and the role of albumin therapy in malnutrition. Albumin is a protein of 584 amino acids. It is highly soluble and has a strong negative charge. Several variants in the amino acid sequence, alloalbumins, coexist with normal albumin. Albumin makes up half the normal intravascular protein mass and is responsible for 75% 80% of the plasma colloid osmotic pressure.2 In a healthy person, 9 12 g of albumin are synthesized in the liver per day. The rate of synthesis is controlled primarily by changes in the colloid osmotic pressure and the osmolality of the extravascular space. Insulin, thyroxine, and cortisol also stimulate the production of albumin; however, growth hormone has no signicant effect on albumin synthesis. Importantly, in severe protein malnutrition, the production of albumin may be decreased.2,3 Albumin is a predominantly extravascular protein with a total extravascular mass of approximately 160 g, despite a lower interstitial concentration compared with serum concentration. The serum concentration of albumin is about 4 g/dL in normal individuals and the total intravascular mass is about 120 g. Under normal circumstances, the albumin concentration in the interstitial space is half that in the intravascular space. The half-life of albumin is 1719 days.2 The catabolism of albumin takes place mainly in the vascular endothelium at a rate of 9 12 g per day, or 4% of total body albumin. The rate of albumin degradation is related to its concentration. Calorie and protein deprivation also accelerate albumin catabolism. Serum levels of albumin may fall during periods of stress, trauma, or sepsis despite its long half-life. The drop may result from accelerated redistribution from the intravascular space, decreased synthesis, and increased catabolism. Injury and infection result in a decrease of serum albumin level of approximately 11.5 g/dL within 37 days.3 An example is the drop in albumin seen in previously healthy patients who sustained head injury and did not receive major uid resuscitation (Fig. 1). This rapid drop in the serum albumin
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Figure 1. Patients with severe head injury had a marked increase in C-reactive protein () and a major decrease in serum albumin (E) during their initial hospitalization. Albumin gradually increased as patients clinically improved at later timepoints. Reprinted from Boosalis MG, Ott L, Levine AS, et al. Relationship of visceral proteins to nutritional status in chronic and acute stress. Crit Care Med. 1989;17(8):741747 with permission from Lippincott Williams & Wilkins.

tion of radiolabeled albumin. Over the rst 2 days, there is a rapid phase of disappearance from the plasma that correlates with the transcapillary exchange rate or 4.5% per hour. The distribution half-time is about 15 hours. Then there is a slower decay of about 3.7% per day with an elimination half time of about 19 days.4 The major physiologic functions of albumin include:3 1. Binding and transport of molecules; 2. Colloid osmotic pressure effect; 3. Free radical scavenging; 4. Platelet function inhibition and antithrombotic effects; and 5. Capillary membrane permeability. Commercially available human albumin is derived from pooled human plasma. Its use is not without potential side effects. Complications associated with albumin administration include uid overload, coagulation defects, hemolysis and myocardial depression, perhaps related to the binding of calcium ions.35 Allergic reactions are rare but may occur, usually to contaminants or to polymers that form during processing. Viral transmission is highly

concentration is further highlighted by initial studies from our group demonstrating a decrease in the serum albumin concentration following a single injection of the pro-inammatory cytokine, tumor necrosis factor, into experimental animals (Fig. 2). Under normal circumstances, albumin circulates from the intravascular space across the capillary wall into the interstitial compartment, and returns to the intravascular space through the lymphatic system. Albumin has a circulation half-life of approximately 16 hours. The movement of albumin across the capillary walls can be measured as the transcapillary escape rate (TER), which is dened as the percentage of intravascular albumin leaving the intravascular compartment per hour. In healthy volunteers, TER is around 4%5%. The TER is determined by the capillary and interstitial free albumin concentrations, the capillary permeability to albumin, solvent and solute movements and, to a lesser degree, the electrical charge across the capillary wall.3 Clearance of proteins from the interstitium is dependent upon the lymphatic ow, which in healthy individuals is around 120 mL/h, with a protein content of about 80% of plasma. The ow of lymph itself is dependent upon interstitial uid pressure, intrinsic pumping by the lymphatic vessels and external compression of vessels by muscle contraction, arterial pulsation, and body movements.2,3 The distribution of exogenous albumin between body compartments has been examined by the injec-

Figure 2. Effect of length of exposure to tumor necrosis factor (TNF) on serum albumin concentration. Rabbits were IV administered either saline or 1 of 2 TNF doses. Blood was collected at 0, 8, 24, and 48 hours after injection. Injection of the vehicle (control) caused no signicant changes in serum albumin concentration. Injection of low-dose TNF caused a signicant reduction in albumin at 24 hours compared with all other time periods (p .05). Injection of high-dose TNF caused signicant (p .05) hypoalbuminemia at 8, 24, and 48 hours compared with baseline. Furthermore, at 24 hours, high-dose TNF administration caused a signicant reduction in albumin compared with low-dose TNF administration. Values are mean SE, n 4. , control; , low-dose TNF; f, high-dose TNF. Reprinted from Hennig B, Honchel R, Goldblum SE, McClain CJ. Tumor necrosis factor-mediated hypoalbuminemia in rabbits. J Nutr. 1988;118:1586 1590 with permission from the American Society for Nutritional Sciences.

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unlikely due to prolonged heat treatment during preparation. Complaints of nausea, fever, or chills usually resolve with a reduction in the rate of transmission or discontinuation of therapy. The risk of aluminum toxicity may be increased by the use of albumin in patients with renal failure. Exogenous albumin administration may decrease endogenous synthesis and increase the rate of albumin degradation.4

Use of Albumin in Volume Resuscitation

Colloids including albumin are widely used as plasma substitutes for short-term replacement of uid volume. In the US, up to 26% of administered albumin is for the treatment of acute hypovolemia (eg, surgical blood loss, trauma, or hemorrhage).5 Successful volume resuscitation in the critically ill patient and restoration of tissue perfusion is essential for patient survival. The optimal composition of uid for volume resuscitation in critically ill patients has been the subject of controversy for decades. Volume for volume, 4.5% albumin is approximately 4 times as effective in expanding the plasma volume as sodium-containing crystalloids.6 Isotonic crystalloid solutions (Ringers lactate, normal saline) distribute within the extracellular space, of which 25% is intravascular and 75% interstitial. The use of crystalloids minimizes the risk of anaphylactic reactions and costs less than colloids. Crystalloids can reduce colloid oncotic pressure and may predispose to pulmonary edema. On the other hand, colloidal solutions (albumin, starches, dextrans, gelatins, blood products, and substitutes) theoretically should remain primarily within the intravascular space and provide an oncotic gradient favoring the entry of water from the interstitial space.7 However, this does not seem to be the case in septic shock due to damage of the vascular endothelium and transcapillary leak. Results from a small study of uid distribution in sepsis showed that 5% albumin and 0.9% normal saline increased the interstitial uid volume equally, and that albumin more effectively increased the intravascular volume.7 In 1998, the Cochrane Injuries Group Albumin Reviewers published a systematic review of randomized, controlled trials.8 Groups of critically ill patients with hypovolemia, burns, or hypoalbuminemia who were given either albumin or plasma protein fraction (PPF) were compared with control groups who received either crystalloid solution or nothing. The main objective of this review was to quantify the effect of human albumin and PPF on mortality in critically ill patients. Only randomized, controlled trials comparing albumin/PPF with no albumin/PPF or with a crystalloid solution in critically ill patients with hypovolemia, burns, or hypoalbuminemia were selected. Thirty randomized trials comprising 1419 patients and 156 deaths were selected for analysis. For each patient category, the risk of death in the albumin treated group was higher than in the comparison group. In the sub-

group of hypovolemic patients, the relative risk of death after albumin administration was 1.46 (95% CI: 0.972.22). For the rest of subgroups including burns and hypoalbuminemia, the relative risk of death was also elevated. The pooled relative risk of death with albumin administration was 1.68 (1.26 2.23). The pooled difference in the risk of death with albumin was 6% (95% CI: 3%9%). When the analysis was repeated to include only the studies that followed adequate allocation concealment (total of 13 trials), the relative risk of death was still higher for each patient category with a pooled relative risk of 1.61 (1.09 2.38). In summary, no evidence that albumin reduces mortality was found. In fact, there was a strong suggestion that it may increase mortality in critically ill patients with hypovolemia, burns, or hypoalbuminemia. The authors postulated that the increased risk of death caused by albumin was related to its anticoagulant properties, increased interstitial oncotic pressure in patients with increased capillary permeability, and the adverse hemodynamic consequences or rapid volume replacement. It was recommended that albumin should not be used outside the context of a rigorously conducted randomized, controlled trial. Several limitations of the Cochrane review were outlined, including the lack of homogenous patient population, the lack of consistency in disease severity and treatment regimens, the lack of correlation between time of death and time of albumin administration, and the fact that mortality was not the primary endpoint in many of the studies in the review.9 Furthermore, in some of the studies, none of the patients in the control group died, which is highly improbable in a study conducted in an intensive care unit. Four of the studies in the review included premature or newborn infants. A recent update of the original meta-analysis by the Cochrane Injuries Group Albumin Reviewers in 2002 included only 1 additional study with 100 additional patients.10 Not surprisingly, it reached the same conclusion as the rst review in 1998. For each patient category, the risk of death was higher in the albumin-treated group. The pooled relative risk of death with albumin administration was 1.52 and the risk of death was increased by 5%.10 A meta-analysis by Wilkes and Navickis published in 2001 compared the use of albumin therapy with crystalloid therapy, no albumin, or lower doses of albumin.1 It included only randomized controlled trials using puried albumin (the Cochrane review included older studies using less pure preparations, such as PPF, that are no longer in clinical use in developed countries) and did not limit the analysis to studies in critically ill patients. Fifty-ve trials involving surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other indications were included with a total of 3504 patients, more than twice the number included in the original Cochrane review. Several of

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the studies reviewed in the hypovolemia group of the Cochrane review were included in the surgery/ trauma group in the Wilkes meta-analysis. Overall, this study detected no difference in mortality between patients treated with albumin and patients treated with other uids. For all trials, the relative risk for death was 1.11 (95% CI: 0.951.28). However, in the subgroups of trials that were judged to be of higher quality (trials with blinding, mortality as an endpoint, no crossover, and 100 or more patients), the relative risk of death was lower (0.73 1.04). In trials with 2 or more of these attributes, the relative risk was further reduced. The contradiction between these 2 large and conicting reviews may be a result of the difculty in demonstrating a benet, lack of benet, or inuence on mortality of a single therapeutic intervention in critically ill patients. In response to these conicting results, the Australian and New Zealand Intensive Care Society, the Institute for International Health of the University of Sidney, and the Australian Red Cross Blood Service designed a large double-blind, randomized, controlled trial to compare the effects of uid resuscitation with 4% albumin or saline on mortality in a heterogeneous population of patients in the intensive care unit (ICU).11 Nearly 7000 patients underwent randomization and were followed for 28 days. Patients with trauma, severe sepsis, or acute respiratory distress syndrome were included. Patients admitted to the ICU after cardiac surgery, liver transplantation, or after the treatment of burns were excluded. Baseline characteristics of the patients were similar as to age, gender, APACHE score, physiologic variables, organ failure, mechanical ventilation requirement, and renal replacement therapy. The trial showed no signicant difference between mortality at 28 days. In terms of morbidity, length of stay in the intensive care unit, or length of stay in the hospital, the difference between the 2 groups was not statistically signicant. The frequency of need for mechanical ventilation, renal replacement therapy, and the time until death were also equivalent. In conclusion, the study provided evidence that albumin and normal saline should be considered clinically equivalent treatments for intravascular volume resuscitation in critically ill patients. In terms of morbidity, a meta-analysis by Haynes in 2003 included 79 randomized trials with a total of 4755 patients.12 The trials were divided into different subgroups including cardiac surgery, noncardiac surgery, hypoalbuminemia, ascites, sepsis, burns, and brain injury. There were a total of 48 trials in the 2 surgical groups that compared the use of albumin vs different crystalloids for volume expansion in order to attain certain hemodynamic endpoints. In cardiac surgery, albumin administration resulted in lower uid requirements, higher colloid oncotic pressure, and reduced pulmonary edema. The use of hydroxyethyl starch increased pulmonary

edema. In noncardiac surgery, uid requirements and pulmonary/intestinal edema were decreased when albumin was given. A recent meta-analysis by Vincent and coworkers in 200413 looked at morbidity in hospitalized patients receiving albumin compared with patients receiving crystalloid, no albumin, or low-dose albumin. The analysis included 71 trials with 3782 patients divided into the categories of surgery or trauma, burns, hypovolemia, high-risk neonates, ascites, and other indications. There was only 1 trial of hypovolemic shock (with 44 patients) that was included in the other indications category. The overall morbidity was signicantly lower in albumin recipients than in control patients with a relative risk of 0.92. When looking at the surgery/trauma group, no effect was demonstrable among these trials.

Albumin Use in Chronic Liver Disease

Albumin infusions have been used in patients with decompensated cirrhosis in 3 clinical situations: 1) to prevent circulatory dysfunction after total paracentesis or serial large volume paracentesis;14 16 2) to decrease frequency of renal impairment and mortality in patients with spontaneous bacterial peritonitis;17 and 3) as part of the treatment regimen for hepatorenal syndrome.18 20 The controversy regarding use of IV albumin is more intense when it is used after paracentesis because the preventable circulatory dysfunction is transitory and mortality is not affected; in addition, the cost of albumin is high ($525 per gram and its supply is limited).21 After serial large volume paracentesis of 5 L each, a patient will receive 30 40 g of albumin; after a total paracentesis (mean volume of 9 L), the patient will receive 54 72 g because albumin is usually given at a dose of 6 8 g per L of ascitic uid removed. When other volume expanders were used (Dextran-70 and polygeline), they were less effective than albumin.22 At this amount, the use of IV albumin infusion remains questionable but not unreasonable, considering that the alternative is very close outpatient follow-up with serial laboratory tests, which is also expensive and often impractical or unrealistic. More recently, IV Terlipressin infusion (1 g/bolus every 8 hours for a total of 3 g over 16 hours) has been used in a randomized pilot study, and was found to be as effective as IV albumin (at a dose of 8 g per L of ascites removed) in preventing postparacentesis circulatory dysfunction. However, the mean volumes of paracentesis were only 6 L and 4.9 L, respectively, and the cost of both therapies was similar (994 vs 1,100).23 Terlipressin is not available in the United States. The use of IV albumin in patients with spontaneous bacterial peritonitis (SBP) is less controversial, but not free of controversy. In a prospective, ran-

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domized study, 126 patients with SBP were assigned treatment with cefotaxime alone (63 patients) or cefotaxime plus IV albumin at 1.5 g/kg at time of diagnosis plus 1 g/kg on day 3 (total 175 g albumin for a 70-kg person).17 Frequency of renal impairment was reduced from 33% to 10%, the in-hospital mortality rate from 29% to 10%, and the 3-month mortality rate from 41% to 22%, with the addition of albumin. For each of these endpoints, the difference was statistically signicant with p .005. The study has been criticized because the authors did not (or failed to report that they did) volume expand the control group with crystalloids. Because it is not known if lesser volumes of albumin or if other types of volume expansion (crystalloids, dextran, etc) can affect mortality in a similar way, clinicians will have great difculty in dismissing the results of this study and are well justied in giving albumin to these patients. New studies are needed to determine if lower doses of albumin or alternative volume expanders are equivalent. The least controversial use of IV albumin is its use as part of a regimen to reverse hepatorenal syndrome (HRS). Hepatorenal syndrome has a very high mortality with a 4-week survival of 20% and 10-week survival of 8%.24 There are 3 medical regimens that have proven to be life saving in patients with HRS; all 3 of them use IV albumin to expand the effective intravascular volume before giving a second drug to increase vascular tone. The rst regimen gives IV albumin at a dose of 1 g/kg to normalize plasma renin activity with repeated infusions as needed, and then adds ornipressin 2 IU/h as a continuous infusion. Most patients had reversal of HRS. Ornipressin is not available in the United States. The second regimen gave IV albumin infusion until the central venous pressure reached 12 mmHg, and then added oral midodrine and subcutaneous octreotide, both given 3 times a day.19 Four-week survival was improved to 80% and HRS was reversed in all patients. The third regimen gave IV albumin until the central venous pressure was above 4 mmHg, repeating infusions to keep it at that level. Then, noradrenaline continuous infusion was started at 0.5 mg/h with increments in dose by 0.5 mg/h every 4 hours until the mean arterial pressure raised by 10 mmHg above baseline and urine output exceeded 50 mL/h. Only 1 of 12 patients failed to respond and the 2-month survival was 50% (vs the 15% expected survival rate).20 Due to the clear impact in survival and the relative noninvasiveness of these regimens, the use of albumin is well justied in this setting. Indeed, our management of renal dysfunction in liver disease has changed drastically over the past few years, and mortality from hepatorenal syndrome has been substantially improved.

Figure 3. Serial serum albumin (E) and prealbumin () levels compared with protein intake (). Although prealbumin levels better reected protein intake, the delay between increased protein consumption and the increase in prealbumin levels was over a week. Thus the albumin level reected the clinical course of the patient, and neither albumin nor prealbumin could be used as an accurate marker of protein intake Reprinted from Boosalis MG, Ott L, Levine AS, et al. Relationship of visceral proteins to nutritional status in chronic and acute stress. Crit Care Med. 1989;17(8):741747 with permission from Lippincott Williams & Wilkins.

Albumin in Nutrition Support and Hypoalbuminemia

Albumin concentrations can decrease rapidly over a few hours secondary to increased loss of albumin and altered distribution between the intra- and extravascular compartments. Altered distribution associated with increased capillary permeability is probably the most frequent cause of hypoalbuminemia in critically ill patients. Decreased albumin concentration secondary to decreased synthesis (eg, severe liver failure) tends to occur over a period of weeks to months.25 Because the serum level of albumin is affected by many factors, serum albumin correlates very poorly with the assessment of nutrition status26 28 (Fig. 3). As an indicator of morbidity and mortality, serum albumin concentration is a reliable tool.29 Hypoalbuminemia has been shown to be associated with increased mortality and morbidity in hospitalized patients and community-dwelling elderly persons.30 In elective surgery, an association between hypoalbuminemia and adverse outcomes has also been recognized for years. Results from the large national Veterans Affairs surgical risk study suggested that serum albumin concentration was a

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better predictor of surgical outcomes than many other preoperative patient characteristics.29 This large study included nearly 55,000 noncardiac surgical cases for which preoperative serum albumin values were reported. Major surgeries included general, vascular, orthopedic, and thoracic. Compared with other risk variables, serum albumin was the strongest predictor of surgical outcomes with an inverse relation between 30-day morbidity and mortality and preoperative serum albumin levels. The provision of adequate nutrition support may take weeks to months in order to raise the serum albumin concentration. The administration of exogenous albumin as adjunctive therapy in hypoalbuminemic patients who are receiving parenteral nutrition has been reviewed. Several randomized, controlled trials evaluating the use of albumin in hypoalbuminemic patients have been included and reviewed repeatedly in several meta-analyses. The 1998 Cochrane Injuries Group Albumin Reviewers reported a higher risk of death in patients receiving albumin as adjunctive to parenteral nutrition with a relative risk of 1.69.8 This subgroup included 9 trials, and 3 of them were performed in newborns. The meta-analysis published by Wilkes in 20011 included only 5 randomized clinical trials in the hypoalbuminemia subgroup with no pediatric trials. Overall, no signicant effect on mortality was detected either across all trials combined or within any of the 6 categories of clinical indications (surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other). In terms of morbidity, 3 large meta-analyses that included the same randomized controlled trials concluded that there was a trend toward reduced morbidity by administering exogenous albumin in hypoalbuminemic patients.31,32 Clinical benet was demonstrated when albumin levels 3 g/dL were attained, thus showing a possible dose dependency.

statistically signicant benet in terms of morbidity.13 The administration of albumin along with antibiotic therapy is signicantly better than antibiotic alone at preventing renal impairment and reducing mortality in patients with cirrhosis and spontaneous bacterial peritonitis.17 Such intervention is now standard of care in our institution. The use of albumin vs other plasma expanders postparacentesis in cirrhotic patients with ascites is still not clear and will be the subject of review by the Cochrane Hepato-Biliary Group.33 This review will assess the benecial and harmful effects of albumin, synthetic colloids, or IV infusion of ascitic uid in combination with paracentesis for the treatment of ascites in cirrhotic patients. The serum albumin level correlates with disease severity and mortality in hospitalized patients. However, there is no support for the use of albumin as a nutrition support product. Further, the serum albumin level unfortunately does not parallel protein or calorie administration with either parenteral or enteral nutrition. Thus, the serum albumin level should not be used as a marker of adequacy of nutrition support. Finally, the use of exogenous albumin in hypoalbuminemic patients may be benecial and possibly dose-dependent. Further studies are needed to delineate the role of albumin in different doses in this particular setting.

Acknowledgments
This work was supported in part by the Department of Veterans Affairs. Dr McClain is supported by the National Institutes of Health Grants AA010762 and AA010496, and a Kentucky Science and Engineering Foundation grant.

References
1. Wilkes M, Navickis R. Patient survival after human albumin administration. Ann Intern Med. 2001;135:149 164. 2. Doweiko J, Nompleggi D. Role of albumin in human physiology and pathophysiology. JPEN J Parenter Enteral Nutr. 1991;15: 207211. 3. Margarson M, Soni N. Serum albumin: touchstone or totem? Anaesthesia. 1998;53:789 803. 4. Nicholson J, Wolmarans R, Park G. The role of albumin in critical illness. Br J Anaesth. 2000;85:599 610. 5. Boldt J. The good, the bad, and the ugly: should we completely banish human albumin from our intensive care units? Anesth Analg. 2000;91:887 895. 6. Horsey P. The Cochrane 1998 albumin reviewnot all it was cracked up to be. Eur J Anaesthesiol. 2002;19:701704. 7. Waikar S, Chertow G. Crystalloids vs. colloids for resuscitation in shock. Curr Opin Nephrol Hypertens. 2000;9:501504. 8. Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomized controlled trials. Br Med J. 1998;317:235240. 9. Horsey P. Albumin and hypovolemia: is the Cochrane evidence to be trusted? Lancet. 2002;359:70 72. 10. Alderson P, Bunn F, Lefebvre C, et al. Albumin Reviewers. Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev. 2004;4: CD001208. 11. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for uid resuscitation in the intensive care unit. N Engl J Med. 2004;350:22472256.

Conclusions
Albumin use in critically ill patients has been the topic of debate for many years and recent publications seem to have answered many questions about indications of albumin therapy considered controversial in the past. The use of albumin infusions vs crystalloids in uid resuscitation has been the subject of several trials. Overall, no difference in survival has been detected.1,11 In terms of morbidity, the role of albumin has not been shown to be signicantly better than the use of crystalloids.11,13 There seems to be enough evidence to consider albumin and normal saline solutions as clinical equivalents. The choice of one over the other seems to be inuenced by the clinicians preference, availability, and cost of the solution. The use of albumin infusions in ascites seems to be benecial. The use of albumin infusions vs no albumin in ascites was reviewed in the meta-analysis published by Vincent et al in 2004 and showed a

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12. Haynes G, Navickis M, Wilkes M. Albumin administration: what is the evidence of clinical benet? A systematic review of randomized controlled trials. Eur J Anaesthesiol. 2003;20:771793. 13. Vincent J, Navickis R, Wilkes M. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med. 2004;32:2029 2038. 14. Luca A, Garc a-Paga n JC, Bosch J. Benecial effects of intravenous albumin infusion on the hemodynamic and humoral changes after total paracentesis. Hepatology. 1995;22:753758. 15. Ruiz-del-Arbol L, Monescillo A, Jimenez W, Gasrcia-Plaza A, Arroyo V, Rodes J. Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis. Gastroenterology. 1997;113:579 586. 16. Salerno F, Badalamenti S, Incerti P, et al. Repeated paracentesis and i.v. albumin infusion to treat tense ascites in cirrhotic patients. A safe alternative therapy. J Hepatol. 1987;5:102108. 17. Sort P, Navasa M, Arroyo V, 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. 18. Guevara M, Gines P, Fernandez-Esparrach G, et al. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology. 1998;27:35 41. 19. Angeli P, Volpin R, Gerunda G, et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999;29:1690 1697. 20. Duvoux C, Zanditenas D, Hezode C, et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study. Hepatology. 2002;36:374 380. 21. Runyon BA. Management of adult patients with ascites caused by cirrhosis. Hepatology. 1998;27:264 272. 22. Gines A, Fernandez-Esparrach G, Monescillo A, et al. Randomized trial comparing albumin, dextran-70 and polygeline in cirrhotic patients with ascites treated by paracentesis. Gastroenterology. 1996;111:10021010.

23. Moreau R, Asselah T, Condat B, et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomized pilot study. Gut. 2002;50:90 94. 24. Gines A, Escorsell A, Gines P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993;105:229 236. 25. Uhing M. The albumin controversy. Clin Perinatol. 2004;31:475 488. 26. Waitzberg D, Correia M. Nutritional assessment in the hospitalized patient. Curr Opin Clin Nutr Metab Care. 2003;6:531538. 27. Downs J, Haffejee A. Nutritional assessment in the critically ill. Curr Opin Clin Nutr Metab Care. 1998;1:275279. 28. Fuhrman P. The albuminnutrition connection: separating myth from fact. Nutrition. 2002;18:199 200. 29. Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as a predictor of operative mortality and morbidity. Arch Surg. 1999;134:36 42. 30. Covinsky K, Covinsky M, Palmer R, Sehgal AR. Serum albumin concentration and clinical assessments of nutritional status in hospitalized older people: different sides of different coins? J Am Geriatr Soc. 2002;50:631 637. 31. Vincent J, Dubois M, Navickis R, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A metaanalysis of cohort studies and controlled trials. Ann Surg. 2003; 237:319 334. 32. Rubin H, Carlson S, DeMeo M. Randomized, double-blind study of intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition (PN). Crit Care Med. 1997;25:249 252. 33. Simonetti RG, Gluud C, Milazzo G, Pagliaro L. Albumin and other plasma expanders for paracentesis treatment of ascites in cirrhotic patients. The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD004039. DOI: 10.1002/14651858. CD004039.

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