VA Class:BL500

ATC Class:B05AA01

AHFS Class:

• Blood Derivatives 16:00

Generic Name(s):

• Albumin Human

Albumin human, a protein colloid, is a sterile solution of serum albumin prepared by fractionating pooled plasma from healthy human donors.133,139,204,205,206,207,208,210,211,212,213,214,215,254,255,256

Hypovolemia

Albumin human solutions are used for plasma volume expansion and maintenance of cardiac output (fluid resuscitation) in the emergency treatment of hypovolemia (with or without shock) when urgent restoration of blood volume is indicated.187,204,205,206,207,208,210,211,212,213,214,215,218,220,221,226,227,254,255,256,295,297,300,301,303,304

The goal of fluid resuscitation is to restore intravascular volume and preserve organ perfusion while minimizing fluid overload complications (e.g., pulmonary edema).187,225 Albumin human, a protein colloid, is one of several options that can be used to restore effective circulating volume.148,187,219,222,225,226,227,228,304,308 Other options include nonprotein colloids (e.g., hetastarch, dextran) and large volume crystalloids (e.g., lactated Ringer's, various sodium chloride-containing solutions).148,187,219,222,225,226,227,228,304,308 When used for fluid resuscitation, the beneficial effects of albumin human are thought to result principally from its contribution to colloid osmotic pressure (i.e., oncotic pressure).148,210,211

Ongoing controversy exists regarding the optimum choice of fluid (i.e., crystalloids, albumin human, nonprotein colloids) for fluid resuscitation in emergency situations.148,187,219,220,222,225,226,227,228,261,299,303,304,308 Protocols used for fluid resuscitation, including the type of replacement fluid, vary widely among health-care facilities148,187,219,220,222,225,226,227,228,261,303,304,308 and may depend on the geographic area (e.g., country) where the patient is being treated.304 Some clinicians state that colloids such as albumin human are preferred because they offer therapeutic advantages over crystalloids, while others recommend use of crystalloids based on cost considerations and lack of established superiority of colloids.148,187,218,219,222,225,226,227,228 The potential advantages of colloids include greater retention in the intravascular space, more rapid and effective plasma volume expansion, and a reduced risk of pulmonary edema.187,211,214,220,225,226,227,228 However, such benefits are theoretical and have not been proven; in addition, the favorable oncotic gradients that colloids provide may be diminished in situations where there is endothelial damage and transcapillary leakage (e.g., in septic shock or burns).187,225,226,228 Clinical studies generally have not shown colloids to be more effective than crystalloids for fluid resuscitation, and costs associated with colloid administration are substantially higher than those associated with crystalloid administration.148,187,219,220,222,225,226,228

Previous pooled analyses of randomized controlled clinical studies have questioned the role and safety of albumin human relative to other colloids and crystalloids in the management of critically ill patients, including those with hypovolemia.134,149,150,151,152,153,218,222 In a pooled analysis of 30 randomized, controlled clinical studies involving 1419 critically ill patients receiving albumin human or plasma protein fraction (with or without crystalloids) that was performed by the Cochrane Injuries Group Albumin Reviewers in 1998, there was no evidence that albumin human reduced mortality compared with control (crystalloid solution alone or no albumin human) in patients with hypovolemia, burns, or hypoproteinemia (hypoalbuminemia).149,151,152,153,166,187 Instead, this analysis revealed evidence suggesting that mortality risk actually may be increased by 6% overall with use of albumin human in these patients.149,151,152 An increased risk of mortality also was observed in each patient population, reaching statistical significance for patients with burns or hypoproteinemia.149,151 As a result of this analysis, the authors151,166 and others149,152,153 cautioned that recommendations for the use of albumin human in critically ill patients should be reevaluated, and such use should be undertaken only after careful consideration, weighing the potential benefits and risks. However, the findings of this study have been criticized for methodologic problems that limit clinical interpretation,188,187 and the clinical studies that were evaluated used many different end points, making it difficult to determine comparative efficacy and safety.187 In a larger, subsequent meta-analysis of 55 randomized, controlled trials comparing albumin human to crystalloid therapy, no albumin, or lower dosages of albumin in 3504 patients from a broad population (e.g., patients with trauma, burns, hypoalbuminemia, or ascites; high-risk neonates; surgery patients), there was no evidence of increased risk of death associated with use of albumin human.221

To resolve conflicting evidence from meta-analyses, a large, multicenter randomized controlled study (the Saline versus Albumin Fluid Evaluation [SAFE] trial) was conducted comparing the effects of normal saline (0.9% sodium chloride) with albumin human in approximately 7000 adults in intensive care units (ICUs) who required fluid resuscitation.222,224,225,226,228 Pediatric patients, burn patients, and those who had undergone liver transplantation or cardiac surgery were excluded from the study.222,224,225,226 Eligible patients who had at least one objective sign of hypovolemia were randomized to receive either albumin human 4% solution (not commercially available in the US) or normal saline for 28 days in addition to maintenance fluids, specific replacement fluids, blood products, or other concurrent interventions as required.222,224,225,226 There was no difference in 28-day mortality (primary outcome), development of organ failure, length of hospital or ICU stay, duration of mechanical ventilation, or duration of renal replacement therapy between patients who received albumin human and those who received normal saline.222,224,225,226,228 Results generally were consistent across subgroups of patients with severe sepsis, trauma, and acute respiratory distress syndrome (ARDS; previously known as adult respiratory distress syndrome), although there was a slight trend towards increased mortality in patients with head trauma who received albumin human and a trend towards reduced mortality in those with severe sepsis who received albumin human.222,299 However, the study was not specifically designed to detect any clinically important differences between subgroups and results of such analysis should be interpreted with caution.222,224,225,228 Based on findings from the SAFE study, the US Food and Drug Administration (FDA) Blood Products Advisory Committee concluded in 2005, that the prior safety issues raised by the Cochrane Injuries Group had been resolved.224 In an updated meta-analysis performed by the Cochrane Albumin Reviewers, there was no difference in overall mortality between albumin human and normal saline in critically ill patients with hypovolemia, burns or hypoalbuminemia.218 There was a suggestion of a higher risk of death with albumin human in patients with burns and hypoalbuminemia (relative risk of 2.4 and 1.38, respectively), but not in patients with hypovolemia (relative risk of 1.01).218 The authors note that the estimate in hypovolemic patients was heavily influenced by results of the SAFE study.218

Based on current evidence, albumin human appears to offer no advantage in terms of survival over crystalloids for fluid resuscitation, although the possibility of a modest benefit or harm cannot be excluded.187,218,219,222,225 Although results of a meta-analysis suggest that albumin human may provide a protective effect in reducing morbidity among acutely ill hospitalized patients, additional study is needed to substantiate these findings and more fully evaluate the effect of albumin human on other clinically important outcomes.223,226,308 Additional studies also are needed to evaluate the use of albumin human in specific groups who were excluded from the SAFE study (e.g., pediatric, burn, liver transplant, cardiac surgery patients).218,219,222,224,225

Hemorrhagic Shock

Albumin human is used for fluid resuscitation in patients with hemorrhagic shock.187,301

Guidelines on use of albumin, nonprotein colloids, and crystalloids issued by the US University Health System (formerly Hospital) Consortium (UHC) in 2000134,187 state that crystalloid solutions are preferred for initial fluid resuscitation in adults with hemorrhagic shock,187 but that nonprotein colloids may be considered if crystalloids (4 L) fail to produce an adequate response within 2 hours.187 These guidelines state that albumin human 5% solution may be used if nonprotein colloids are contraindicated.187

Crystalloids and colloids should not be considered substitutes for blood or blood components when oxygen-carrying capacity is reduced and/or when replenishment of clotting factors or platelets is necessary.134,170,187 Transfusion with whole blood or packed red blood cells (RBCs) should be initiated as soon as possible when there is active hemorrhage and/or substantial anemia.204,205,207,208,210,211,214,215,254,255,256

Nonhemorrhagic (Maldistributive) Shock

Albumin human has been used for fluid resuscitation in patients with nonhemorrhagic (maldistributive) shock, including septic shock.187,250,261,295,297,299,300 Severe sepsis or septic shock with hypotension or signs of hypoperfusion requires early, vigorous fluid resuscitation to restore tissue perfusion and normalize oxidative metabolism.250,261

The UHC guidelines state that crystalloids should be considered first-line treatment in adults with nonhemorrhagic (maldistributive) shock and that nonprotein colloids and albumin human should be used with caution in those with systemic sepsis.187 These guidelines also state that, in the presence of capillary leak with pulmonary and/or severe peripheral edema, use of up to 4 L of crystalloid solution is appropriate before using colloids.187 If albumin human is used for acute management of nonhemorrhagic shock, the possibility that it may have a potentially detrimental effect on edema in patients with increased capillary permeability or capillary leak should be considered.152,168,187

Other experts state that either crystalloids or colloids can be used for fluid resuscitation in patients with septic shock.250,251,261,295,297,300 However, additional study is needed since there is no evidence-based support from prospective, randomized studies to clearly identify which type of fluid is superior for fluid resuscitation in patients with septic shock.250,251,261,297,298,299,300 Although there is some evidence that adult or pediatric patients with severe infection and shock who receive albumin human for fluid resuscitation have lower mortality compared with those who receive crystalloids,222,261,297,299,300 most studies to date comparing the relative efficacy of crystalloids, albumin human, and nonprotein colloids in patients with septic shock are hampered by difficulties in controlling the effects of concomitant therapy and were not designed or adequately powered to examine mortality as a primary outcome.187,300

Thermal Injury

Albumin human has been used for fluid resuscitation in burn patients.187,218,302,305,306,307,309

Fluid resuscitation is an essential component of burn therapy;187,306 however, the optimum regimen of crystalloids, colloids, electrolytes, and fluid for the management of patients with thermal (burn) injuries has not been clearly established.204,205,207,208,211,213,214,215,218,302,305,306,307,309 There is ongoing controversy regarding the role of and most appropriate time to initiate colloids for fluid resuscitation in burn patients.187,305,306,307,309 Some clinicians believe that use of colloids during the initial hours after a burn is inappropriate because much of the volume is drawn into the interstitial space secondary to increased permeability of surrounding unburned tissue; others believe that colloids should be administered from the beginning of fluid resuscitation.187,305,306,307 In patients with thermal injury, crystalloids generally are recommended during the first 24 hours to reverse acute hypovolemia and maintain hemodynamic stability.187,204,205,207,211,213,214,309 Beyond 24 hours, use of colloids also may be employed to prevent hemoconcentration, combat electrolyte imbalances, and counteract the protein deficit that occurs in severe burns.204,205,207,208,210,211,213,214,215,309 To avoid complications of over-resuscitation (“fluid creep”), such as abdominal compartment syndrome and ARDS, the least amount of fluid necessary to maintain adequate organ perfusion should be used.305,306,307,309

The UHC guidelines recommend that crystalloids be used for initial fluid resuscitation in adults with thermal injury, but state that nonprotein colloids may be added if burns extend over more than 30% of body surface area and more than 4 L of crystalloid solution has been administered 18-26 hours following initial injury.187 These guidelines state that albumin human may be considered if nonprotein colloids are contraindicated.187 Guidelines issued by the American Burn Association state that the addition of colloids to burn resuscitation protocols may be beneficial in terms of decreasing total fluid volume requirements, but randomized, controlled trials are needed to clearly establish other benefits.307

Additional study is needed to determine the acute-phase and short-term differences between albumin human, crystalloids, and nonprotein colloids for fluid resuscitation in pediatric burn patients.187 Albumin human does not appear to decrease morbidity and mortality when used in pediatric burn patients187 and, depending on the preparation used, may result in aluminum accumulation in infants.140,143,144,187 (See Aluminum Content under Cautions: Precautions and Contraindications.)

Kidney Disease

Nephrosis and Nephrotic Syndrome

Albumin human is used as an adjunct to diuretic therapy to treat edema in patients with acute nephrosis refractory to cyclophosphamide and steroid therapy.187,204,205,206,208,214,215,245,255,256

Cardinal features of nephrotic syndrome include albuminuria, hypoalbuminemia, and edema.187 Urinary albumin loss, with a resultant decrease in plasma oncotic pressure, was thought to be associated with the development of edema and secondary renal sodium retention.187 Additional evidence indicates that decreased hepatic production and increased renal catabolism are responsible for hypoalbuminemia, while renal sodium retention is responsible for edema.187 The principal goal of therapy for nephrotic syndrome is treatment of the underlying cause; when the cause does not respond to therapy, alleviation of pathophysiologic manifestations, including sodium retention and edema, is important.187

Diuretic therapy is the treatment of choice for symptomatic management of nephrotic syndrome.187 The UHC guidelines recommend short-term adjunctive use of albumin human with diuretics in adults with nephrotic syndrome who have acute, severe peripheral and/or pulmonary edema that is unresponsive to diuretics alone;187 however, the possibility of a potentially detrimental effect on edema should be considered.152,168,187

Albumin human has no role in the management of chronic nephrosis since parenteral albumin is rapidly excreted renally with no relief of the chronic edema or effect on the underlying renal lesion.134,204,205,213,214

Hemodialysis

Albumin human has been used as an adjunct to hemodialysis in long-term hemodialysis patients with oncotic or volume deficits or in those experiencing shock or hypotension who cannot tolerate substantial volumes of sodium chloride solutions.204,205,206,212,214,261,265,266

Intradialytic hypotension, a complication of hemodialysis (especially in long-term hemodialysis patients), usually is managed by volume expansion through the use of crystalloids (e.g., 0.9% sodium chloride solutions, hypertonic sodium chloride solutions), nonprotein colloids, or albumin human.261,265,266 Some experts state that colloids may be preferred to crystalloids for dialysis-related hypotension and maintenance of hemodynamics in chronic dialysis patients.261 Others recommend 0.9% sodium chloride solution as first-line therapy if treatment of intradialytic hypotension is indicated in maintenance hemodialysis patients.265 This recommendation is based on results of a randomized, controlled study that indicated that albumin human 5% solution is not superior to 0.9% sodium chloride solution for treatment of symptomatic hypotension in maintenance hemodialysis patients with a previous history of intradialytic hypotension.265,266

The UHC guidelines state that albumin human should not be used for intradialytic blood pressure support.187 If adults undergoing hemodialysis experience shock symptoms, the UHC guidelines state that crystalloid solutions are preferred for initial fluid resuscitation, but that nonprotein colloids may be considered if crystalloids (4 L) fail to produce an adequate response within 2 hours.187 These guidelines state that albumin human 5% solution may be used if nonprotein colloids are contraindicated.187

Kidney Transplantation

Albumin human has been used intraoperatively in conjunction with crystalloids for volume expansion in kidney transplant patients.148,187 However, there is no conclusive evidence from controlled, randomized studies that albumin human given during and/or after renal transplant surgery improves outcome.148,187

Liver Disease

Cirrhotic Ascites and Paracentesis

Albumin human is used to prevent central volume depletion following paracentesis in adults with cirrhosis who require removal of large volumes of ascitic fluid.187,214,226,236,254,255,256,261,286,287,310

Diet modification (e.g., sodium restricted to 2 g daily) combined with oral diuretic therapy is the first-line therapy for adults with cirrhosis and ascites.187,236,286 An initial large-volume paracentesis may be necessary in addition to sodium restriction and oral diuretic therapy if tense ascites is present in new-onset disease.236,286 In patients with refractory ascites (fluid overload unresponsive to sodium restriction and high-dose oral diuretic therapy or that recurs rapidly after paracentesis), serial therapeutic paracentesis may be indicated to control ascites.236,287 A single paracentesis involving removal of no more than 4-5 L of fluid usually can be performed safely without postparacentesis colloid support; however, when larger volumes (greater than 5 L) are removed, use of albumin human may be considered and usually is recommended to decrease the risk of postparacentesis circulatory dysfunction and maintain arterial blood volume.187,236,261,264,286,287 Nonprotein colloids also have been used for plasma expansion following paracentesis and have been recommended as alternatives to albumin human;187,236,286,310 however, some clinicians state that albumin human may be preferred236,286,310 since there is some evidence that the incidence of postparacentesis circulatory dysfunction following large-volume paracentesis may be less with albumin human than with some nonprotein colloids.286,310 The UHC guidelines and some clinicians state that when less than 3-5 L of ascites fluid has been removed and repletion of intravascular volume is of concern, adjunctive use of a crystalloid (e.g., sodium chloride solution) should be considered following paracentesis.187,287

Although albumin human has been used alone (without large-volume paracentesis) in patients with cirrhosis in an attempt to control or prevent recurrence of ascites,187,236,285,236 guidelines issued by the American Association for the Study of Liver Diseases (AASLD) and UHC state that such use is not recommended.187,236 In addition, the UHC guidelines state that albumin human should not be used for the treatment of noncirrhotic postsinusoidal portal hypertension.187

Despite the presence of hypoalbuminemia, albumin human has no role in the management of chronic cirrhosis†.21,134,148,204,205,206

Hepatorenal Syndrome

Albumin human has been used in conjunction with vasoconstrictors for the treatment of type I hepatorenal syndrome† in patients with cirrhosis.226,236,243,244,264,286,287,288,289,290,291,292,293,294 Type I hepatorenal syndrome is characterized by acute, rapidly progressing renal failure caused by intrarenal vasoconstriction and usually requires liver transplantation if not reversed.236,244,286,287,288,289,293,294 There is some evidence that use of regimens that include albumin human to expand intravascular volume and vasoconstrictors to increase vascular tone (e.g., terlipressin [not commercially available in the US], octreotide and midodrine, norepinephrine) in patients with rapidly progressing type I hepatorenal syndrome may improve renal function and delay the need for or improve outcomes after liver transplantation.226,236,243,244,264,286,288,289,290,291,292,293,294 Although additional study is needed, the AASLD and other experts state that a regimen of albumin human used in conjunction with vasoconstrictors (e.g., terlipressin, octreotide and midodrine) should be considered in the treatment of type I hepatorenal syndrome.236,264,289,294

Data are limited regarding the use of albumin human alone or in conjunction with vasoconstrictors in the management of type II hepatorenal syndrome† (characterized by moderate and slowly progressive renal failure and typically associated with refractory ascites), and additional study is needed to determine if albumin human has a role in this form of the disease.236,289,291,294

Spontaneous Bacterial Peritonitis

Albumin human has been used as an adjunct to anti-infectives in the treatment of spontaneous bacterial peritonitis† in patients with cirrhosis and ascites.187,236,267,268,269,286,289,293

Spontaneous bacterial peritonitis is a complication that can occur in patients with cirrhosis and ascites, develops without a contiguous source of infection (e.g., intestinal perforation, intra-abdominal abscess), requires prompt empiric anti-infective treatment, and may result in potentially fatal, progressive renal impairment or hepatorenal syndrome.236,267,286,287 There is some evidence that adjunctive use of albumin human for volume expansion in addition to appropriate anti-infective treatment in patients with spontaneous bacterial peritonitis may decrease the risk of renal impairment and death.236,261,267,268,269,286 Such use is controversial and additional study is needed.187,267,268,269,270,289 The AASLD recommends that albumin human be used in addition to appropriate anti-infective treatment (e.g., cefotaxime) in patients who have ascitic fluid polymorphonuclear (PMN) counts of 250 cells/mm³ or higher and also have serum creatinine concentrations greater than 1 mg/dL, BUN greater than 30 mg/dL, or total bilirubin concentrations greater than 4 mg/dL.236

Acute Liver Failure

Albumin human has been used in patients with acute liver failure.205,206,213,296 In such patients, albumin human may provide a stabilizing effect and serve the dual purpose of supporting plasma colloid osmotic pressure as well as binding excess plasma bilirubin in the uncommon situation of rapid loss of liver function, with or without coma.204,205,213 Use of albumin human in patients with acute liver failure should be individualized based on the clinical situation.206 When fluid resuscitation is indicated in patients with acute liver failure, some experts recommend use of colloids (e.g., albumin human) instead of crystalloids.296

Hepatic Resection

Albumin human has been used for postoperative fluid support in patients undergoing hepatic resection†.187 Surgical resection of the liver results in substantial blood loss and, depending on the preoperative functional status of the liver, decreased albumin production capacity.187 The UHC guidelines state that crystalloids should be considered first-line therapy for maintenance of effective circulating volume following hepatic resection in adults and, if crystalloids have no effect and anemia and/or coagulopathy are present, then packed RBCs and fresh frozen plasma should be considered before use of albumin human.187 However, the UHC guidelines state that albumin human is appropriate to maintain effective circulation volume following major hepatic resection (more than 40%) in adults and also is indicated if clinically important edema develops secondary to use of crystalloids.187

Liver Transplantation

Albumin human has been used to control ascites and severe pulmonary and peripheral edema in liver transplant recipients†.187 Because of excessive blood loss, volume expanders such as crystalloids, blood products, nonprotein colloids, and albumin human may be required intraoperatively during liver transplantation.187 The UHC guidelines state that albumin human may be used in adult liver transplant recipients when serum albumin is less than 2.5 g/dL, pulmonary capillary wedge pressure is less than 12 mm Hg, and hematocrit exceeds 30%.187

Hypoproteinemia

Albumin human has been used in the management of severe hypoalbuminemia (with or without edema) in an attempt to restore serum albumin concentrations to within the normal range.204,205,207,208,210,211,212,214,215,254,255,266 However, in the absence of clinically important hypovolemia, albumin human should not be used to correct temporary protein deficits resulting from redistribution of albumin.211,214,231

The principal goal of therapy in hypoproteinemia (hypoalbuminemia) is treatment of the underlying cause; albumin human may be used to provide symptomatic relief and prevent acute complications.204,205,206,207,208,210,211,212,214,215,226 Hypoproteinemia can occur in association with various clinical conditions (e.g., surgery, sepsis, chronic liver failure, chronic renal impairment) and is a result of inadequate production, increased catabolism, redistribution, and/or excessive loss of albumin.204,205,206,208,210,211,214,215,226,231 Use of albumin human in patients with severe hypoalbuminemia simply in an attempt to increase serum albumin concentrations to within the normal range (i.e., the patient does not exhibit manifestations of hypovolemia) cannot be recommended based on current evidence; instead, the cause of the underlying hypoalbuminemia should be identified and treated.147,152 To varying degrees, albumin human may relieve edema associated with hypoproteinemia by increasing colloid osmotic pressure and producing diuresis.207,214 However, if albumin human is administered to hypoproteinemic patients who do not have an accompanying volume deficit, there is a potential risk of fluid overload.231

Albumin human should not be used for the treatment of hypoproteinemia associated with chronic cirrhosis, chronic nephrosis, malabsorption, protein-losing enteropathies, pancreatic insufficiency, or malnutrition, unless there is a concomitant indication that warrants use.204,205,211,213,214

Although albumin human has been used to treat neonatal hypoalbuminemia†, data are insufficient to determine whether routine use of albumin human reduces mortality or morbidity in preterm neonates with hypoalbuminemia.231

Nutritional Support

Although there is some evidence suggesting that serum albumin concentration is an accurate measure of patient prognosis using indicators of morbidity and mortality, and that albumin concentrations can be safely and effectively restored using total parenteral nutrition (TPN) supplemented with albumin human, other evidence has led many clinicians to question the importance of albumin supplementation.187,226 Serum albumin concentration is a poor indicator of nutritional status and it may take several weeks to months to see an increase in the serum albumin concentration following adequate nutritional support.226 Albumin human is not recommended for use as a supplemental caloric protein source in patients requiring nutritional support.21,148,187,204,205,206,208,210,211,213,214,215,226 Iatrogenic elevation of serum albumin concentrations above 4 g/dL may increase the overall catabolic rate.21,207 In general, oral, enteral, and/or parenteral nutrition with amino acids and treatment of underlying disorders will restore plasma protein concentrations more effectively than albumin human.208,210,215 However, patients with diarrhea associated with enteral feeding intolerance may benefit from parenteral administration of albumin human if they have severe diarrhea (more than 2 L daily) and a serum albumin concentration less than 2 g/dL or if diarrhea occurs despite a trial of short-peptide and elemental formulas and other causes of diarrhea have been excluded.134,148,177,187

Neonatal Hyperbilirubinemia

In the treatment of neonatal hyperbilirubinemia, including hemolytic disease of the newborn (erythroblastosis fetalis), albumin human (20 or 25% solution) is used as an adjunct to exchange transfusions in an attempt to bind unconjugated bilirubin and decrease the risk of kernicterus.187,204,205,206,208,214,215,255,256 Albumin human has been administered prior to exchange transfusion (as a primer) or during the procedure (as a substitute for a portion of the blood) in infants with severe hemolytic disease of the newborn.187,204,205,208,214,215 Because there is some evidence that administration of albumin human prior to exchange transfusion is less efficient in bilirubin removal and may increase the risk of volume overload, the UHC guidelines recommend that albumin human be administered during the procedure if it is used as an adjunct to exchange transfusion.187 Albumin human should be used with caution in hypervolemic infants.204,205,214 (See Hypervolemia/Hemodilution under Cautions: Precautions and Contraindications.)

Albumin human should not be used if neonatal hyperbilirubinemia is treated using phototherapy without exchange transfusion.134,187

Crystalloids and nonprotein colloids do not share the bilirubin-binding properties of albumin human and should not be considered alternatives for adjunctive treatment of hyperbilirubinemia in neonates.187

Ovarian Hyperstimulation Syndrome

Albumin human (20 or 25% solution) is used as a plasma expander for fluid management in the treatment of severe ovarian hyperstimulation syndrome (OHSS).255,256 Severe OHSS is a life-threatening complication of gonadotropin treatment characterized by growth of multiple large ovarian follicles with massive extravascular protein-rich fluid shift; this can lead to hypovolemia, hemoconcentration, ascites, oliguria, and electrolyte disturbances and may result in potentially fatal thromboembolic complications and acute respiratory distress syndrome.232,237,238,239,240,241,242 Albumin human 20 or 25% solution has been recommended in the treatment of severe OHSS if 0.9% sodium chloride solutions fail to achieve or maintain hemodynamic stability and adequate urine output.238,255,256

Albumin human also has been investigated for prevention of severe OHSS in high-risk women undergoing ovulation induction†.187,232,237,238,239,240,241,242,258,259,260 However, additional study is needed to more fully evaluate the benefits and risks of albumin human for prevention of OHSS.187,232,260 One meta-analysis of 5 randomized, controlled clinical studies in high-risk women (i.e., younger than 35 years of age, multifollicular development, high serum estradiol concentrations, nonobesity, polycystic ovary disease) indicated that administration of a single IV infusion of albumin human 20 or 25% immediately before or after oocyte retrieval appeared to reduce the risk of severe OHSS in such patients.232,237,238,239,240,241,242 This meta-analysis indicated that use of albumin human in women at high risk may prevent 1 case of severe OHSS in every 18 women who receive such prophylaxis.232 However, other studies and meta-analyses evaluating use of albumin human for prevention of OHSS in high-risk women failed to demonstrate a statistically significant reduction in the occurrence of severe OHSS in those receiving albumin human.258,259,260

Acute Respiratory Distress Syndrome and Acute Lung Injury

Albumin human (20 or 25% solution) has been used in conjunction with a diuretic in the management of acute respiratory distress syndrome (ARDS, previously known as adult respiratory distress syndrome).148,171,177,204,205,206,208,214,215,255,256 However, use of albumin human in patients with ARDS is controversial because of the risk of aggravating interstitial fluid accumulation and other possible detrimental pulmonary effects.134,171,172,173,177 Although uncertainty exists regarding the precise indication for albumin human in patients with ARDS,208,214,215,261 some manufacturers state that albumin human may have a therapeutic effect if used in conjunction with a diuretic in patients with pulmonary overload accompanied by hypoalbuminemia.208,214,215

Albumin human has been used in conjunction with furosemide in the management of hypoproteinemic patients with acute lung injury† (ALI) and has resulted in improved oxygenation and hemodynamic stability in some patients.261,262,263,283 Some experts state that conservative fluid management or restriction is appropriate for most patients with hemodynamically stable ALI/ARDS;261,283,284 however, although conclusive data are lacking, a regimen of colloids and diuretics may be considered in those with hypo-oncotic ALI/ARDS.261,283

Sequestration of Protein Rich Fluids

Albumin human has been used for volume and oncotic replacement in conditions associated with sequestration of protein rich fluid or third-spacing (e.g., acute peritonitis, pancreatitis, mediastinitis, extensive cellulitis).204,205,211,213,214

Albumin human has been used as an adjunct to anti-infectives in the treatment of spontaneous bacterial peritonitis† in patients with cirrhosis and ascites.187,236,267,268,269,286 (See Spontaneous Bacterial Peritonitis under Uses: Liver Disease.)

Albumin human may be useful in the early treatment of shock associated with acute hemorrhagic pancreatitis or peritonitis.211

The UHC guidelines state that albumin human is not recommended in the treatment of acute or chronic pancreatitis.187

Cardiac Surgery

Albumin human has been used as a pump prime for preoperative dilution of blood prior to cardiopulmonary bypass procedures,187,204,205,206,208,210,212,213,214,271,281,282 usually in conjunction with a crystalloid.187,204,205,213,214,215,271,282 However, studies generally have shown only marginal or no additional benefit when colloids were added to crystalloids in the preoperative regimen.187 The UHC guidelines state that crystalloids alone usually are the regimen of choice for priming cardiopulmonary bypass pumps,187 although use of nonprotein colloids in addition to crystalloids may be preferable in cases in which it is extremely important to avoid pulmonary shunting.187

Albumin human also has been used in cardiac surgery patients to restore fluid balance during surgery and in the postoperative period.187,208,210,215,281 Although albumin human has been recommended prior to or during cardiopulmonary bypass208,210,215 and there is some evidence that use of albumin human in cardiopulmonary bypass patients is associated with less postoperative bleeding than use of hetastarch (a nonprotein colloid),281 there are no data establishing a clear benefit for use of albumin human over use of crystalloids alone.208,210,215 For postoperative volume expansion after cardiac surgery, the UHC guidelines state that crystalloids are preferred, followed in descending order of preference by nonprotein colloids and then albumin human.187

Neurosurgery and Cerebral Injury

Albumin human has been used for hemodilution to maintain or improve cerebral perfusion in the treatment of subarachnoid hemorrhage†, acute ischemic stroke†, traumatic brain injury†, and in other neurosurgical patients†.174,175,176,187,261,272,273,274,275,276,277,278,279,280 Various fluid protocols have been used in an attempt to prevent secondary ischemia after subarachnoid hemorrhage, severe ischemic stroke, or severe traumatic brain injury.187,272,275,276,277,278,279 Although improved clinical outcomes have been reported in some patients,187,272,275,276,277,278,279 results have been conflicting and there is no clear evidence to date from adequately controlled, randomized studies that hemodilution decreases mortality or improves functional outcome in survivors of acute ischemic stroke.187,274

The UHC guidelines state that crystalloids are preferred for maintenance of cerebral perfusion pressure in the treatment of cerebral vasospasm associated with subarachnoid hemorrhage, cerebral ischemia, or head trauma in adults; however, if cerebral edema is a concern, albumin human 25% solution should be used.187 These guidelines state that patients with elevated hematocrits should receive crystalloids first to increase intravascular volume, creating a state of hypervolemia and hemodilution, and that those with hematocrits less than 30% should receive packed RBCs to increase the intravascular volume and maintain cerebral perfusion pressure.187 If volume therapy alone is inadequate to maintain cerebral perfusion pressure, vasopressor therapy may be necessary.187

Plasmapheresis

Albumin human is used in conjunction with large-volume plasma exchange as protein volume replacement in plasmapheresis† procedures involving exchange of more than 20 mL of plasma per kg in one session or more than 20 mL/kg weekly in multiple sessions.148,187 The UHC guidelines state that nonprotein colloids and crystalloids may substitute for some of the albumin human in therapeutic plasmapheresis procedures and should be considered cost-effective exchange media.187 Some evidence indicates that nonprotein colloids (e.g., hetastarch 3%) are comparably effective and tolerated relative to albumin for small- or large-volume plasma exchange.134,178,179,180,181

Erythrocyte Resuspension

Albumin human has been used to resuspend large volumes of previously frozen or washed RBCs prior to administration or during certain types of exchange transfusion to provide sufficient volume and/or avoid excessive hypoproteinemia during the transfusion.204,205,214

Administration

Albumin human solutions are administered by IV infusion.204,205,206,207,208,210,211,212,213,214,215,254,255,256

The concentration of albumin human administered (i.e., albumin human 5, 20, or 25% solution) depends on the fluid and protein requirements of the patient and is determined in part by whether there is a greater need for volume or oncotic replacement.21,204,205,208,210,213,215,254,255,256

Albumin human 5% solutions usually are preferred in the treatment of acute blood volume deficits in the absence of adequate or excessive hydration.204,205,208,213,215

Albumin human 20 or 25% solutions may be preferred when there is an oncotic deficit or when hypovolemia is long standing (e.g., due to treatment delay) and hypoalbuminemia exists in the presence of adequate or excessive hydration.204,205,208,210,213,215 Albumin human 20 or 25% solutions also are preferred when the drug is being used for its binding rather than oncotic effects (e.g., in the treatment of neonatal hyperbilirubinemia).204,205,206,208,211,212,214,215

When used for the treatment of hypovolemia, albumin human solutions are most effective in well-hydrated patients.208,215,254,255,256 If the patient is dehydrated, albumin human 5% solution usually is preferred;204,205,208,213,215 if albumin human 20 or 25% solutions are used in dehydrated patients, additional crystalloids or other fluids should be administered.204,205,206,207,208,214,215

IV Infusion

Depending on the indication, protein and fluid requirements, sodium restrictions, and availability, commercially available albumin human solutions can be administered undiluted or can be further diluted in a compatible IV solution (e.g., 0.9% sodium chloride, 5% dextrose).37,124,125,126,127,128,129,130,131,132,133,134,135,136,137,184,204,205,206,207,208,214,215

Whenever dilution of albumin human is considered necessary (e.g., to prepare a 5% solution from a 25% solution),208 the oncotic and osmotic properties as well as the tonicity of the resultant dilution must be considered.37,124,125,126,127,128,129,130,131,132,133,134,136,137,138,184

Because of the risk of potentially life-threatening hemolysis, albumin human must not be diluted using hypotonic solutions such as sterile water for injection.125,127,128,129,130,133,134,135,136,137,138,184,204,205,206,207,208,210,214,215,254,255,256 (See Oncotic, Osmotic, and Tonicity Considerations under Cautions: Precautions and Contraindications.)

If necessary, albumin human 5% solutions may be prepared from albumin human 25% solutions by adding 1 volume of the 25% solution to 4 volumes of 0.9% sodium chloride injection or 5% dextrose injection.208 Since albumin human 25% solution diluted with 0.9% sodium chloride or 5% dextrose results in 5% dilutions that are approximately isotonic and iso-oncotic with citrated plasma, these diluents are preferred for such dilutions.133,136,137

When sodium restriction is necessary, albumin human solutions should be administered either undiluted or diluted in a sodium-free carbohydrate solution such as 5% dextrose.133,184,204,205 However, because administration of large volumes of albumin human 5% prepared by diluting 25% solutions with 5% dextrose could result in hyponatremia and potentially serious adverse effects (e.g., cerebral swelling),136,137 0.9% sodium chloride generally should be used as the preferred diluent when administration, particularly rapid administration, of large volumes is anticipated (e.g., during plasmapheresis or plasma exchange) and the fluid and electrolyte status of the patient permits.136,137,184

Prior to administration, albumin human solution should be inspected visually for particulate matter and discoloration and should not be used if it appears turbid or contains sediment.204,205,206,207,208,210,211,212,213,214,215,254,255,256

Albumin human should be used immediately after the vial or container is opened.254,255,256 Albumin human solutions should be discarded if more than 4 hours have elapsed since the container was first entered.204,205,206,207,208,210,211,212,213,214,215

The manufacturers' prescribing information should be consulted for specific directions regarding use of IV administration sets and filters.204,205,206,207,208,210,211,212,213,214,215,254,255,256 Some manufacturers state that adequate filtration is required;206,208,210,212,215 other manufacturers state that filtration is not required.254,255,256

Albumin human may be administered in conjunction with whole blood, plasma, or dextrose, sodium lactate, or sodium chloride injections.135,204,205,206,207,208,210,211,212,213,214,215 Albumin human should not be mixed with parenteral nutrient solutions,257 protein hydrolysates,204,205,206,208,210,211,212,213,214,215 amino acid solutions,204,205,211,213,214 or solutions containing alcohol.204,205,206,208,210,211,212,213,214,215 (See Chemistry and Stability: Stability.)

Rate of Administration

The rate of IV infusion of albumin human should be individualized based on the indication, concentration of albumin human solution used, and clinical status and response of the patient.204,205,206,207,208,210,211,212,213,214,215,254,255,256 The manufacturers' information should be consulted for specific information regarding recommended rates of administration.204,205,206,207,208,210,211,212,213,214,215,254,255,256

When albumin human 5% solution is used for the treatment of hypovolemic shock in patients with greatly reduced blood volume, a rapid IV infusion rate may be necessary initially to provide clinical improvement and restore normal blood volume.210,211,212 However, in patients with a history of cardiac or vascular disease, some manufacturers suggest a slow infusion rate (e.g., 5-10 mL/minute) to avoid an increase in blood pressure that is too rapid.210 In patients with normal or slightly low blood volume, some manufacturers suggest that albumin human 5% solution should be administered at a rate of 1-2 mL/minute.211,212

When albumin human 20 or 25% solution is used for the treatment of hypovolemic shock in patients with greatly reduced blood volume, a rapid IV infusion rate may be necessary initially to provide clinical improvement and restore normal blood volume.206 However, in patients with normal or slightly low blood volume, some manufacturers state that the IV infusion rate should not exceed 1 mL/minute since more rapid infusion rates may result in circulatory overload or pulmonary edema.206,207,208,215 A slower infusion rate also is recommended in patients with hypertension.207 When albumin human 20 or 25% solution is used in hypoproteinemic patients with approximately normal blood volume, a maximum infusion rate of 2 mL/minute (Plasbumin^®-20, Plasbumin^®-25)204,205 or 2-3 mL/minute (Albuminar^®-25) has been recommended.207

When albumin human solutions are used in pediatric patients, some manufacturers recommend that the IV infusion rate should be reduced to 25% of the usual adult rate.206,212

Dosage

Dosage of albumin human is variable and should be individualized based on the specific indication, concentration of albumin human solution used, and clinical status and response of the patient.204,205,206,207,208,210,211,212,213,214,215,254,255,256 The manufacturers' information should be consulted for specific dosage recommendations.204,205,206,207,208,210,211,212,213,214,215,254,255,256

Predetermined formulas for dosage calculation generally are avoided since they assume that the same dose is appropriate for all patients.187 In the absence of active hemorrhage, total daily albumin dosage should not exceed the theoretical amount present in normal plasma volume (i.e., 2 g/kg body weight).21,204,205,208,210,214,215,254,255,256

Response to therapy should be determined by factors such as hemodynamic response (e.g., blood pressure), degree of pulmonary congestion, and hematocrit.207,211,214 Serum protein concentrations usually do not need to be monitored during albumin human therapy, but may be useful in some cases of hypoproteinemia to estimate the total body albumin deficit and guide selection of dosage.214

Hypovolemia

Adults

When albumin human is used for the treatment of hypovolemic shock in adults, some manufacturers recommend the following initial dose.206,208,210,211,212,215,254,255,256 The dose may be repeated in 15-30 minutes if the response is inadequate.206,208,210,212,215,254,255,256

Albumin human 5% solution: 12.5-25 g (250-500 mL of a 5% solution).210,211,212,254

Albumin human 20% solution: 25 g (125 mL of a 20% solution).255

Albumin human 25% solution: 25-50 g (100-200 mL of a 25% solution).206,208,215,256

Pediatric Patients

Some manufacturers recommend that 25-50% of the usual initial adult dosage be used and adjusted according to the child's weight and clinical condition.206,212 The manufacturers' prescribing information should be consulted for specific dosing recommendations in children.206,208,210,211,212,213,215

If albumin human is used for the treatment of hypovolemic shock in pediatric patients, some clinicians recommend a dose of 0.5-1 g/kg (maximum of 6 g/kg in 24 hours or 250 g in 48 hours).311

Albumin human 5% solution: Some manufacturers recommend an initial dose of 0.5-1 g/kg212,213,254 or 2.5-12.5 g254 for the treatment of hypovolemia in pediatric patients. One manufacturer recommends a dose of 12-20 mL/kg for infants and young children and 250-500 mL for older children.210 The dose may be repeated after 15-30 minutes if the response is inadequate.210,254

Albumin human 20% solution: One manufacturer recommends an initial dose of 0.5-1 g/kg or 2.5-12.5 g for the treatment of hypovolemia in pediatric patients.255 The dose may be repeated after 15-30 minutes if the response is inadequate.255

Albumin human 25% solution: Some manufacturers recommend an initial dose of 0.5-1 g/kg206,256 or 2.5-12.5 g256 for the treatment of hypovolemia in pediatric patients. The dose may be repeated after 15-30 minutes if the response is inadequate.208,215,256

Thermal Injury

The optimum regimen of crystalloids, colloids, electrolytes, and fluid for the management of patients with thermal (burn) injuries has not been clearly established.204,205,207,208,211,213,214,215,218,302,305,306,307,309 In addition, the duration of replacement therapy in burn patients varies, depending on such factors as the extent of protein loss from renal excretion, denuded skin areas, and decreased albumin production.21,204,205,207,213,214

A suggested goal of burn therapy is to maintain a plasma albumin concentration of 2-3 g/dL and plasma oncotic pressure of 20 mm Hg (equivalent to a total plasma protein concentration of 5.2 g/dL).204,205,213,214

If albumin human is used in burn patients, one manufacturer recommends that large volumes of crystalloids be given initially to maintain plasma volume; after 24 hours, albumin human may be added using an initial dose of 25 g with dosage adjusted thereafter to maintain a plasma protein concentration of 2.5 g/dL or a serum protein concentration of 5.2 g/dL.254,255,256

Kidney Disease

Acute Nephrosis

If albumin human 20 or 25% solution is used as an adjunct to treat edema in the management of acute nephrosis, some manufacturers recommend a dosage of 20 or 25 g once daily for 7-10 days (in conjunction with an appropriate diuretic).204,205,214,255,256

Hemodialysis

If albumin human 20 or 25% solution is used for the treatment of a volume or oncotic deficit in patients undergoing long-term hemodialysis or for the treatment of shock or hypotension in these patients, some manufacturers state that the usual dose is about 100 mL204,205 (the initial dose should not exceed 100 mL).214 Patients must be carefully monitored for signs of circulatory overload.204,205,212,214

Liver Disease

Cirrhotic Ascites and Paracentesis

If albumin human is used to prevent central volume depletion following large-volume paracentesis in adults with cirrhosis and ascites, the usual dose is 6-8 g per liter of ascitic fluid removed.187,236,254,255,256,286 A single paracentesis involving removal of no more than 4-5 L of fluid usually can be performed safely without colloid support; however, use of albumin human may be considered when larger volumes (greater than 5 L) are removed.187,236,261,264,286,287

Hepatorenal Syndrome

Although albumin human used in conjunction with vasoconstrictors has been recommended for the treatment of type I hepatorenal syndrome† in patients with cirrhosis (see Hepatorenal Syndrome under Uses: Liver Disease), optimum regimens have not been identified.226,236,243,244,264,286,287,288,289,290,291,292,293,294

If albumin human is used in conjunction with vasoconstrictors in adults with type I hepatorenal syndrome†, some experts recommend a dosage regimen that includes an initial dose of 1 g/kg (up to 100 g) of albumin human on day 1, followed by 20-40 g once daily.289,293,294 If a response is obtained, treatment should be continued until serum creatinine concentrations are less than 1.5 mg/dL.294 Albumin human may be discontinued if serum albumin concentrations exceed 4.5 g/dL and should be discontinued if pulmonary edema is present.289

Spontaneous Bacterial Peritonitis

Although albumin human has been used as an adjunct to anti-infectives in the treatment of spontaneous bacterial peritonitis† in patients with cirrhosis and ascites, optimum regimens have not been identified.236,267,268,269,286,289,293

The American Association for the Study of Liver Diseases (AASLD) recommends that adults with ascitic fluid polymorphonuclear (PMN) counts of 250 cells/mm³ or higher and clinical suspicion of spontaneous bacterial peritonitis who also have serum creatinine concentrations greater than 1 mg/dL, BUN greater than 30 mg/dL, or total bilirubin concentrations greater than 4 mg/dL receive 1.5 g/kg of albumin human within 6 hours of detection and another dose of 1 g/kg on day 3.236

Hypoproteinemia

Adults

If albumin human 5% solution is used for the treatment of hypoproteinemia in adults, one manufacturer recommends a dose of 50-75 g.254

If albumin human 20 or 25% solution is used for the treatment of hypoproteinemia in adults, some manufacturers recommend a daily dosage of 50-75 g (e.g., 250-375 mL of a 20% solution or 200-300 mL of a 25% solution).204,205,207,255,256 Larger amounts may be required in patients with severe hypoproteinemia who continue to lose albumin.204,205 Some manufacturers recommend a maximum dosage of 2 g/kg daily.208,210

The total body albumin deficit (including hidden extravascular albumin deficiency) should be considered when determining the dosage of albumin human necessary to reverse hypoalbuminemia.208,210,254,255,256 When using serum albumin concentrations to estimate the protein deficit in hypoproteinemia, some manufacturers recommend that the body albumin compartment be calculated based on 80-100 mL/kg body weight to account for any hidden extravascular albumin deficits.208,210,215

Pediatric Patients

If albumin human is used for the treatment of hypoproteinemia in pediatric patients, some clinicians recommend a dosage of 0.5-1 g/kg given by IV infusion over 0.5-2 hours and repeated once every 1-2 days as needed (maximum of 6 g/kg in 24 hours or 250 g in 48 hours).311

For the treatment of hypoproteinemia in children, one manufacturer recommends that albumin human 20 or 25% be given in a dosage of 25 g daily.204,205 Larger amounts may be required in patients with severe hypoproteinemia who continue to lose albumin.204,205

Neonatal Hyperbilirubinemia

If albumin human 20 or 25% solution is used as an adjunct to exchange transfusions for the treatment of neonatal hyperbilirubinemia, including hemolytic disease of the newborn (erythroblastosis fetalis), the recommended dose is 1 g/kg.204,205,206,208,214,215,255,256 The dose of albumin human has been given prior to exchange transfusion (as a primer) or during the procedure (as a substitute for a portion of the blood).187,204,205,208,214,215,255,256 (See Uses: Neonatal Hyperbilirubinemia.)

Ovarian Hyperstimulation Syndrome

If albumin human 20 or 25% solution is used for fluid management in the treatment of severe ovarian hyperstimulation syndrome (OHSS), one manufacturer recommends that 50-100 g be given by IV infusion over 4 hours every 4-12 hours as necessary.255,256

Acute Respiratory Distress Syndrome

If albumin human 20 or 25% solution is used in conjunction with a diuretic in the management of fluid overload in adults with acute respiratory distress syndrome (ARDS; previously known as adult respiratory distress syndrome), one manufacturer recommends that 25 g be given by IV infusion over 30 minutes and repeated at 8-hour intervals for 3 days, if necessary.255,256

Cardiac Surgery

The optimum fluid regimen to ensure adequate blood volume during cardiopulmonary bypass is unclear.206,214 (See Uses: Cardiac Surgery.) Some manufacturers recommend that albumin human and crystalloid pump prime solutions be adjusted to achieve a plasma albumin concentration of 2.5 g/dL and a hematocrit of 20%.204,205,213,214

Erythrocyte Resuspension

If albumin human 20 or 25% solution is used to resuspend red blood cells (RBCs) during certain types of exchange transfusion or to resuspend large volumes of previously frozen or washed RBCs, some manufacturers recommend that approximately 20-25 g of albumin be added per liter of isotonic suspended RBCs immediately prior to transfusion.204,205,214 Greater amounts may be required in patients with preexisting hepatic impairment or hypoproteinemia.204,205

Adverse Effects

Although adverse effects occur infrequently in patients receiving albumin human,204,205,207,211,213,214,252,253 serious adverse effects (e.g., anaphylaxis, circulatory failure, cardiac failure, pulmonary edema), including some fatalities possibly related to albumin human, have been reported rarely.208,210,215,252,253,254,255,256

The most common206,212,254,255,256 adverse effects reported in patients receiving albumin human include anaphylactoid reactions,254,255,256 fever,204,205,206,207,208,211,210,212,213,214,215,254,255,256 chills,204,205,206,207,208,210,211,212,213,214,215,254,255,256 rash,206,207,212,254,255,256 nausea,206,207,208,210,211,212,214,215,254,255,256 vomiting,206,207,208,210,212,215,254,255,256 tachycardia,206,208,210,212,215,254,255,256 and hypotension.206,207,208,210,211,212,214,215,252,254,255,256

Anaphylaxis,207,208,210,215,252,253,254,255,256 urticaria,204,205,207,208,210,211,213,214,215,254,255,256 pruritus,207,208,210,215,254,255,256 angioneurotic edema,254,255,256 erythema or flushing,207,208,210,215,254,255,256 dysguesia,208 increased salivation,207 hyperhidrosis,254,255,256 headache,208,211,214,254,255,256 confusion,254,255,256 loss of consciousness,254,255,256 pulmonary edema,254,255,256 dyspnea,208,254,255,256 and bronchospasm207 have been reported during postmarketing surveillance.

Albumin human has variable effects on respiration, blood pressure, and heart rate.204,205,206,207,208,210,211,212,213,214,215 Hypotension,206,207,211,212,214,252,254,255,256 hypertension,254,255,256 circulatory failure,254,255,256 tachycardia,206,212,254,255,256 bradycardia,254,255,256 congestive heart failure,254,255,256 and cardiac failure254,255,256 have been reported. Rapid IV infusion of albumin human may cause vascular overload212 with resultant pulmonary edema.212,254,255,256 (See Hypervolemia/Hemodilution under Cautions: Precautions and Contraindications.)

Several cases of hemolysis (e.g., during or after plasmapheresis) and at least one death probably related to hemolysis have been reported following administration of as little as 270 mL of an albumin human 5% solution that had been prepared extemporaneously by diluting albumin human 25% with sterile water.124,125,126,127,129,130,133,138,184 Such dilutions are markedly hypotonic with respect to blood, with calculated resultant sodium concentrations of 26-32 mEq/L.124,125,126,127,129,130,133 (See Oncotic, Osmotic, and Tonicity Considerations under Cautions: Precautions and Contraindications.)

Precautions and Contraindications

Albumin human is contraindicated in patients hypersensitive to albumin,204,205,206,207,208,210,211,212,213,214,215,254,255,256 any ingredient in the formulation,208,210,215,254,255,256 or any component of the container.254,255,256 (See Sensitivity Reactions under Cautions: Precautions and Contraindications.)

Albumin human is contraindicated in patients with severe anemia206,207,208,210,211,212,215 or with cardiac failure206,207,208,210,211,212,215 in the presence of normal or increased intravascular volume.206,212 Certain individuals are at particular risk of circulatory overload, including those with stabilized chronic anemia, congestive heart failure, or renal insufficiency.204,205,213 (See Hypervolemia/Hemodilution under Cautions: Precautions and Contraindications.)

Because of the risk of aluminum accumulation, the manufacturer states that Buminate^® 25% should not be used in patients with chronic renal impairment.215 (See Aluminum Content under Cautions: Precautions and Contraindications.)

Use of sterile water for injection for dilution of commercially available albumin human solutions is contraindicated because of the risk of potentially life-threatening hemolysis and acute renal failure.125,127,128,129,130,133,134,135,136,137,138,184,204,205,206,207,208,210,214,215,254,255,256 (See Oncotic, Osmotic, and Tonicity Considerations under Cautions: Precautions and Contraindications.)

Risk of Transmissible Agents in Plasma-derived Preparations

Because albumin human is prepared using pooled human plasma, it is a potential vehicle for transmission of human viruses (e.g., hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV], human immunodeficiency virus [HIV]) and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or related agents such as variant CJD (vCJD).192,194,204,205,206,207,208,210,211,212,213,214,215,254,255,256 Although donor plasma is screened for certain viruses and all currently available albumin human preparations undergo viral elimination/inactivation processes (e.g., pasteurization) to further reduce the risk of transmission of infectious agents, a potential for transmission of infectious agents still remains.204,205,206,207,208,210,211,212,213,214,215,254,255,256

Because no purification method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be removed or inactivated by the manufacturing processes currently used, clinicians should discuss the risks and benefits of albumin human with the patient.204,205,206,207,208,210,211,212,213,214,215 Any infection believed to have been transmitted by albumin human should be reported to the manufacturer.204,205,207,208,210,211,213,214,215

Risk of Hepatitis and Human Immunodeficiency Virus Infection

Although albumin human is prepared from human plasma and is a potential vehicle for transmission of the causative agents of viral hepatitis and HIV infection,204,205,206,207,208,210,211,212,213,214,215,254,255,256 the risk of transmission of viral diseases with plasma-derived albumin human is considered extremely remote.192

Studies using plasma-derived coagulation factor preparations indicate that improved donor screening practices and viral elimination/inactivation procedures (e.g., pasteurization) have resulted in plasma-derived preparations with greatly reduced risk for transmission of HBV, HCV, and HIV viruses.190 There have been no documented cases of transmission of enveloped viruses (including HBV, HCV, and HIV) or nonenveloped viruses (including HAV and parvovirus B19) associated with commercially available albumin human.192,206,207,208,210,211,212,214,215 However, transmission of nonenveloped viruses (HAV, parvovirus B19) has been documented following administration of plasma-derived coagulation factors.190 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications, in Antihemophilic Factor [Human] 20:28.16.)

Risk of Creutzfeldt-Jakob Disease or Variant Creutzfeldt-Jakob Disease

Because albumin human is prepared from human blood, it theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or other related agents such as variant CJD (vCJD).191,192,204,205,206,207,208,210,211,212,213,214,215,254,255,256 CJD is a rare, but invariably fatal, degenerative disease of the CNS associated with a poorly understood transmissible agent.191,192,193 The nature of this agent is not completely known, but it is highly resistant to current methods of viral inactivation applied to plasma-derived products; the effect, if any, of fractionation procedures on the agent is not known.123 CJD may be acquired by exogenous (usually iatrogenic) exposure to infectious material or may be familial, caused by a genetic mutation of the prion protein gene.192 There is some evidence that infected individuals may harbor the causative agent for up to 30 years before becoming symptomatic.192 A variant of CJD (vCJD) was first identified in the United Kingdom in 1996.192 The clinical presentation and neuropathologic changes associated with vCJD are different than those of CJD and include an earlier age of onset, absence of diagnostic EEG changes, and detectable abnormal prion protein in lymphoid tissue.192,194

There are no documented cases of CJD or vCJD transmitted through plasma-derived preparations (including plasma-derived albumin human) and the theoretical risk for transmission of CJD with commercially available albumin human is considered extremely remote.120,121,122,123,191,192,193,204,205,206,207,208,210,211,212,213,214,215 However, there have been 3 probable cases of vCJD acquired through transfusion of human red blood cells (RBCs) identified by an ongoing epidemiologic review being conducted in the United Kingdom.202 One of these patients developed symptoms of vCJD 6.5 or 7.8 years, respectively, after receiving non-leukodepleted RBCs from 2 different donors; the donors developed clinical symptoms approximately 40 and 21 months after donating.202 The third probable case of transfusion-associated vCJD had no clinical symptoms of the disease prior to death, but abnormal prion protein was found in postmortem lymphoid tissue (5 years after RBC transfusion); the donor involved in this case had made the RBC donation 18 months before the onset of their clinical symptoms.202 Although attempts to transmit CJD to nonhuman primates via blood transfusion have failed, bovine spongiform encephalopathy (BSE) has been transmitted to at least one sheep through blood transfusion.192,193

CJD has been transmitted in humans by transplantation of cornea or dura mater from infected individuals, injection of growth hormone (somatropin) derived from human pituitary of infected individuals, or the reuse of surface EEG electrodes contaminated by use on an infected individual.121,123 The disease also has been transmitted experimentally in rodents and primates by intracerebral injection of the buffy coat cell portion of blood, homogenates of brain or cornea, whole blood, or untreated CSF from a known infected individual.121

Certain lots of plasma products, including coagulation factors, albumin human, plasma protein fraction, and immune globulin IV (IGIV), produced from blood derived from donors with probable CJD were withdrawn from the market during 1995.120,121 Withdrawal of the implicated products was seen by the US Food and Drug Administration (FDA) as a prudent interim measure pending further analysis of the relative risks and benefits of such plasma products.120 A similar withdrawal of certain lots of Buminate^® 25% was made by the manufacturer in 1997 when it was discovered that a healthy plasma donor who contributed to the plasma pools from which these lots of albumin human were derived had a history of having received a dura mater transplant; this was done as a precautionary measure only, since there was no evidence of CJD in the transplant donor and no cases of CJD associated with products derived from the transplant recipient's plasma.146

Tests are being developed to detect CJD and vCJD infection in blood and plasma donors.192 Until such donor screening tests are available for these diseases, the FDA has recommended interim preventive measures that include specific guidelines for deferral of blood and plasma donors with possible exposure to CJD and vCJD that are based on geographic considerations and guidelines for product retrieval, quarantine, and disposition that are based on consideration of risk in the donor and product and the effect that withdrawals and deferrals might have on the supply of blood, blood components, and plasma derivatives.192

For further information on CJD and vCJD precautions related to blood and blood products, the FDA's guidance for industry on this topic should be consulted ([Web]).192

Risk of West Nile Virus

It is unlikely that West Nile Virus (WNV) could be transmitted through commercially available plasma-derived preparations since WNV is an enveloped virus, like HCV, which is known to be inactivated by the purification and viral elimination/inactivation procedures used in the manufacture of these preparations.196,197 However, there is evidence that WNV can be transmitted in transplanted organs (e.g., heart, liver, kidney) and blood products (e.g., whole blood, packed RBCs, fresh frozen plasma).195,196,198,199 WNV has been isolated from frozen plasma obtained from a blood donor subsequently found to have WNV, indicating that the virus can survive in frozen blood components.196

Beginning in 2003, specific tests to screen donated blood for WNV became available in the US.196,200,201 The FDA also recommends additional measures to assess donor suitability to help screen out potential blood donors who have past or present manifestations that suggest WNV illness.196 These recommendations apply to whole blood and blood components intended for transfusion and blood components, including recovered plasma, source leukocytes, and source plasma intended for use in further manufacturing into injectable or noninjectable products.196

Because of the possible transmission of WNV through organ transplants and blood transfusions, any case of WNV that occurs in a patient who received organs, blood, or blood products within the 8 weeks preceding onset of the illness should be reported to CDC through state and local health authorities and serum or tissue samples should be retained for later studies.195,196 In addition, cases of WNV infection occurring in blood or organ donors within 2 weeks after their donation should be reported to CDC.195,196

For further information on WNV precautions related to blood and blood products, the FDA's guidance for industry on this topic should be consulted ([Web]).196

Sensitivity Reactions

If an allergic or hypersensitivity reaction (e.g., anaphylaxis) occurs or is suspected, albumin human should be discontinued immediately and appropriate therapy initiated as indicated.207,208,210,215,254,255,256 Epinephrine should be readily available in case acute hypersensitivity occurs.254,255,256

Patients should be advised that albumin human should be discontinued immediately if allergic symptoms (e.g., rash, hives, itching, breathing difficulties, coughing, nausea, vomiting, decrease in blood pressure, increased heart rate) occur.254,255,256

Latex Sensitivity

Some packaging components of certain albumin human preparations (e.g., Buminate^® 5%, Buminate^® 25%) contain natural latex proteins in the form of natural rubber latex.210,215 Health-care personnel should take appropriate precautions if these albumin human preparations are administered to individuals with a history of latex sensitivity.233,234,235

Some individuals may be hypersensitive to natural latex proteins found in a wide range of medical devices, including packaging components, and the level of sensitivity may vary depending on the form of natural rubber present;233,234,235 rarely, hypersensitivity reactions to natural latex proteins have been fatal.234,235

Hypervolemia/Hemodilution

Hypervolemia may occur if the dosage and IV infusion rate of albumin human are not adjusted based on the patient's volume status.254,255,256 Rapid IV infusion of albumin human solutions may cause vascular overload.206,208,212,215

Albumin human should be used with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk for the patient (e.g., decompensated cardiac insufficiency, hypertension, esophageal varices, pulmonary edema, hemorrhagic diathesis, severe anemia, renal and postrenal anuria).206,210,215,254,255,256

Albumin human should be administered with caution in patients with low cardiac reserve (e.g., cardiac disease)204,205,206,207,212 and in those who do not have albumin deficiency.207 Albumin human should be administered with great caution in patients with chronic anemia, hypertension, or renal insufficiency.206,207,211,214

Patients should be closely observed for signs of increased venous pressure such as pulmonary edema.206,210,211,212,213,214

At the first clinical sign of possible cardiovascular overload (e.g., headache, dyspnea, increased blood pressure, jugular venous distention, elevated central venous pressure, pulmonary edema), albumin human infusion should be immediately stopped and the patient reevaluated.210,254,255,256

Hemodynamic Monitoring

Hemodynamic performance should be monitored closely during albumin human therapy,208,210,215,254,255,256 and the patient evaluated for evidence of cardiac, respiratory, or renal failure or increasing intracranial pressure.208,210,215,254,255,256

Arterial blood pressure and pulse rate, central venous pressure, pulmonary artery occlusion pressure, urine output, electrolytes, hemoglobin, and hematocrit should be monitored frequently.254,255,256

In postoperative or injured patients, a rapid rise in blood pressure following administration of albumin human may reveal bleeding points that were not apparent at lower blood pressure.204,205,206,207,208,210,212,213,215 To prevent hemorrhage and shock, such patients should be observed carefully and treated appropriately.204,205,206,207,208,210,212,213,215

Anemia and Coagulation Abnormalities

If hemorrhage has occurred in a patient receiving albumin human, relative anemia may be present and should be controlled by supplemental administration of compatible whole blood or RBCs.254,255,256

If comparatively large volumes of fluid are being replaced with albumin human, coagulation parameters and hematocrit must be monitored and adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets, erythrocytes) ensured.208,210,215,254,255,256

Electrolyte Imbalance

Compared with albumin human 5% solution, albumin human 20 or 25% solutions are relatively low in electrolytes.255,256

Electrolyte status should be monitored in patients receiving albumin human, and appropriate steps taken to restore or maintain electrolyte balance.208,210,215,254,255,256

Commercially available albumin human preparations contain 130-160 mEq of sodium per liter.36,37,204,205,206,207,208,210,211,212,213,214,215,254,255,256

Oncotic, Osmotic, and Tonicity Considerations

When dilution of albumin human is necessary (e.g., to prepare a 5% solution from a 25% solution), the oncotic and osmotic properties as well as the tonicity of the resultant dilution must be considered.37,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,184 Because the membrane of erythrocytes is not perfectly semipermeable, it can permit the passage of water (solvent) molecules and solutes; as a result, solutions that are iso-osmotic with blood are not necessarily isotonic with blood.131,132 Substantially hypotonic solutions when admixed with erythrocytes result in the inward passage of water causing the cells to swell and finally burst (hemolyze), releasing hemoglobin.131,132 Such hemolysis occurs when erythrocytes are admixed in vitro with albumin human solutions containing less than 90 mEq of sodium per L;37,127 the risk of such hemolysis depends on the sodium concentration, not on the suspending medium (albumin) or cell concentration.37,131,132

When albumin human 25% is diluted with 0.9% sodium chloride injection or 5% dextrose injection, resulting 5% dilutions are approximately isotonic and iso-oncotic with citrated plasma; therefore, these diluents are preferred if such dilutions are considered necessary (e.g., if commercially available albumin human 5% solution cannot be obtained).133,136,137,204,205,208 Although sterile water occasionally was used in the past to dilute albumin human solutions (e.g., to adjust the sodium content when restriction of intake of the electrolyte was considered necessary),36,37 sterile water must not be used to dilute albumin human.125,126,127,128,129,130,133,134,135,136,137,138,184,204,205,206,207,208,210,214,215,254,255,256 Depending on the relative proportions of albumin human and diluent, dilutions with sterile water may be dangerously hypotonic, carrying the risk of life-threatening hemolysis, particularly if large volumes of markedly hypotonic dilutions are inadvertently administered.37,124,125,126,127,128,129,130,131,132,133,138,184,207 Several cases of hemolysis (e.g., during or after plasmapheresis) and at least one death probably related to the hemolysis have been reported following administration of as little as 270 mL of an albumin human 5% solution that had been prepared by inappropriately diluting a 25% solution with sterile water.124,125,126,127,129,130,133,138,184 Such dilutions are markedly hypotonic with respect to blood, with calculated resultant sodium concentrations of 26-32 mEq/L.124,125,126,127,129,130,133 In the hypotonic environment, shearing forces produced by the plasmapheresis procedures may have contributed to hemolysis in these cases.126,127,133,184 Potentially life-threatening acute renal failure can result from the toxic effects of hemoglobin (released from hemolyzed erythrocytes) in the renal tubules.125,126,127,134,184

Albumin human dilutions with substantially reduced tonicity should not be used as replacement fluids in plasmapheresis procedures or other situations where administration of large volumes and resultant replacement of a significant fraction of the patient's blood volume could result.125,126,127,128,129,130,133,136,137,138,184 When sodium restriction is necessary, 5% dextrose injection is the diluent of choice for albumin human solutions.133,184,204,205 However, because administration of large volumes of albumin human 5% solution prepared by diluting 25% solutions with 5% dextrose could result in hyponatremia and potentially serious adverse effects (e.g., cerebral swelling),136,137 0.9% sodium chloride generally should be used as the preferred diluent when administration of large volumes is anticipated (e.g., during plasmapheresis or plasma exchange) and the fluid and electrolyte status of the patient permits, particularly if rapid infusion is expected.136,137,184 The use of more physiologic diluents (e.g., those closely resembling plasma) also has been suggested as an alternative for diluting albumin human for use in plasmapheresis or plasma exchange.136

If sterile water is used for other situations to dilute albumin human (e.g., when only small volumes are to be infused) and unless other diluents are used concomitantly to raise the final tonicity to a clinically acceptable level, the resultant tonicity of the solution must be considered and any potential risks (e.g., hemolysis, acute renal failure) weighed carefully.37,128,129,130,133

Aluminum Content

Aluminum has been detected as a contaminant in albumin human solutions, and aluminum accumulation and associated toxicity (e.g., hypercalcemia, osteodystrophy with associated fracturing osteomalacia, severe progressive encephalopathy) have been reported in some patients with renal failure receiving albumin human (e.g., via plasmapheresis procedures).101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,140,141,144,145,215

The possibility that aluminum could accumulate in patients with impaired renal function should be considered.101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,140,141,142,143,144,145

Aluminum concentrations in albumin human solutions have varied widely from brand to brand and lot to lot, and reportedly may range up to 323-1830 mcg/L.101,106,141,144,145

Because of the risk of aluminum accumulation, the manufacturer states that Buminate^® 25% should not be used in patients with chronic renal impairment.215

Certain commercially available albumin human preparations are labeled as containing no more than 200 mcg/L of aluminum (AlbuRx^® 5 or 25%, Albutein^® 5 or 25%, Plasbumin^® 5, 20, or 25% [low aluminum formulations]).206,211,212,214,247,248,249 It has been suggested that preparations containing no more than 200 mcg/L of aluminum may be preferred in patients at high risk for aluminum toxicity (e.g., neonates, premature infants, geriatric adults, dialysis patients and others with impaired renal function, patients receiving total parenteral nutrition, burn patients).246

Pediatric Precautions

The manufacturers of Albuminar^® and Plasbumin^® state that safety and efficacy of albumin human have not been established in pediatric patients.204,205,207,213

The manufacturers of Buminate^® and Flexbumin^® state that, although specific pediatric safety studies have not been performed, the safety of albumin human has been demonstrated in children receiving dosages appropriate for the child's body weight.208,210,215

Some manufacturers state that data regarding use of albumin human in pediatric patients, including premature infants, are limited.254,255,256 Clinicians should weigh the benefits and risks206,212 and use albumin human in pediatric patients only when clearly needed.254,255,256

Albumin human has been used as an adjunct to exchange transfusions in the treatment of neonatal hyperbilirubinemia, including hemolytic disease of the newborn (erythroblastosis fetalis),187,204,205,206,208,214,215 but should not be used if neonatal hyperbilirubinemia is treated using phototherapy without exchange transfusion.134,187 (See Uses: Neonatal Hyperbilirubinemia.) Albumin human should be used with caution in hypervolemic infants .204,205,214

Some clinicians state that albumin human 25% solution is contraindicated in preterm infants because of the risk of intraventricular hemorrhage.311

If albumin human is used in neonates or premature infants, a preparation with low aluminum may be preferred246 because of the risk of aluminum accumulation and associated toxicity.141,142,143 (See Aluminum Content under Cautions: Precautions and Contraindications.)

Geriatric Precautions

Clinical studies of albumin human did not include sufficient numbers of geriatric patients 65 years of age or older to determine whether they respond differently than younger patients.254,255,256

Pregnancy, Fertility, and Lactation

Pregnancy

Animal reproduction studies have not been performed with albumin human.204,205,206,207,208,210,211,212,213,214,215,254,255,256 It is not known whether albumin human can cause fetal harm when administered during pregnancy204,205,206,207,208,210,211,212,213,214,215,254,255,256 or during labor or delivery.254,255,256 Potential risks and benefits for the specific patient should be considered,208,210,215 and albumin human should be used in pregnant women or during labor and delivery only if clearly needed.204,205,206,207,208,210,211,212,213,214,215,254,255,256 One manufacturer states that there is no evidence for any contraindications specifically associated with reproduction, pregnancy, or the fetus.211,214

Fertility

It is not known whether albumin human can affect reproductive capacity.204,205,206,207,208,210,211,212,213,214,215,254,255,256

Lactation

It is not known whether albumin human is distributed into milk.254,255,256 Albumin human should be used with caution in breast-feeding women and only when clearly needed.254,255,256

Specific drug interaction studies have not been performed using albumin human.208,210,215,254,255,256

Angiotensin-converting Enzyme Inhibitors

Patients receiving angiotensin-converting enzyme (ACE) inhibitors are at increased risk of atypical reactions (e.g., flushing, hypotension) to the drugs if they undergo therapeutic plasma exchange with albumin human replacement.182 It has been suggested that this interaction may result from prekallikrein activator (PKA, a metabolite of factor XII) present in albumin human, which activates prekallikrein to bradykinin; metabolism of bradykinin is inhibited by ACE inhibitors, thus resulting in accumulation of this naturally occurring vasoactive peptide.182 Because of the risk of atypical reactions, ACE inhibitors should be withheld for at least 24 hours prior to plasma exchange in which large volumes of albumin human are administered.182

Pharmacology

Serum albumin is an important factor in the regulation of plasma volume and tissue fluid balance through its contribution to the colloid oncotic pressure of plasma.204,205,206,207,208,210,211,212,213,214,215 Albumin, a highly soluble globular protein with a relatively low molecular weight (66,500), exerts 70-80% of the colloidal oncotic pressure of normal plasma.206,208,210,211,212,215

Albumin human 5% solution is iso-oncotic with normal human plasma and will expand circulating blood volume by an amount approximately equal to the volume infused.210,211,212,213 IV administration of concentrated albumin human solutions causes a shift of fluid from the interstitial spaces into the circulation.204,205,206,207,208,214,215 When used for the treatment of hypovolemia, albumin human solutions are most effective in well-hydrated patients.208,215,254,255,256 When administered IV to a well-hydrated patient, each volume of albumin human 20 or 25% solution draws about 2.5 or 3.5 volumes of additional fluid, respectively, into the circulation within 15 minutes, reducing hemoconcentration and blood viscosity.204,205,206,207,208,215 The extent and duration of volume expansion produced by albumin human is dependent on the initial blood volume.204,205,206,207,208,210,212,215 In patients with reduced circulating blood volumes (as from hemorrhage or loss of fluid through exudates or into extravascular spaces), hemodilution persists for many hours, but in patients with normal blood volume, excess fluid and protein are lost from the circulation within a few hours.204,205,206,207,208,210,212,215

Although albumin is a protein, it provides only modest nutritive effect.21

Albumin binds and functions as a carrier of intermediate metabolites (including bilirubin), trace metals, some drugs, dyes, fatty acids, hormones, and enzymes, thus affecting the transport, inactivation, and/or exchange of tissue products.20,21,204,205,208,213,230,231

Chemistry and Stability

Chemistry

Albumin human, a protein colloid, is a sterile solution of serum albumin prepared by fractionating pooled plasma from healthy human donors.36,37,133,139,204,205,206,207,208,210,211,212,213,214,215,254,255,256 Albumin human commercially available in the US meets standards established by the US Food and Drug Administration (FDA).36,37,204,205,207,213 No less than 96% of the total protein in the product is albumin.139,254,255,256

Depending on the manufacturer, albumin human solutions occur as clear to slightly opalescent, pale straw to amber or brownish fluids which may have a slight greenish tint.208,210,215,254,255,256 The pH of albumin human solutions is adjusted to 6.4-7.4 with sodium carbonate, sodium bicarbonate, sodium hydroxide, and/or acetic acid.206,207,208,210,212,215 The commercially available preparations contain no preservatives or antimicrobial agents, but do contain stabilizers (e.g., caprylic acid, sodium caprylate, sodium acetyltryptophanate).36,37,204,205,206,207,208,210,211,212,213,214,215,254,255,256

In the US, albumin human is commercially available as 5, 20, or 25% solutions;204,205,206,207,208,210,211,212,213,214,215,254,255,256 other concentrations (e.g., 4% solutions) are commercially available in other countries.250 Because of the risks associated with administration of hypotonic solutions, commercially available 5, 20, and 25% solutions of albumin human contain 130-160 mEq of sodium per liter.36,37,139 (See Oncotic, Osmotic, and Tonicity Considerations under Cautions: Precautions and Contraindications.) Albumin human 5% solutions are approximately isotonic and iso-oncotic with normal human plasma;210,211,212,213,255 albumin human 20 and 25% solutions are oncotically equivalent to approximately 4 and 5 times the volume of normal human plasma, respectively.204,205,206,207,208,214,215,254,256

Plasma used for preparation of albumin human undergoes viral screening procedures, and albumin human is pasteurized at 60°C for 10-11 hours to reduce the viral infectious potential of the preparation.204,205,206,207,208,210,211,212,213,214,215,254,255,256 However, no method has been shown to be totally effective in removing the risk of viral infectivity from plasma-derived preparations.204,205,206,207,208,210,211,212,213,214,215,254,255,256 (See Risk of Transmissible Agents in Plasma-derived Preparations under Cautions: Precautions and Contraindications.)

Stability

Albumin human solutions should be stored in tight containers at the temperature recommended by the manufacturer or indicated on the label and should be protected from light.204,205,206,207,208,210,211,212,213,214,215,254,255,256 Most commercially available 5, 20, or 25% solutions of albumin human should be stored at 30°C or less.204,205,206,208,210,211,212,213,214,215

Albumin human solutions should not be frozen;204,205,206,207,208,210,211,212,213,214,215,254,255,256 solutions that have been frozen should not be used.204,205,210,213 Albumin human solutions should not be used if they appear turbid or contain sediment.37,135,139,204,205,206,207,208,210,211,212,213,214,215,254,255,256 The solutions do not contain preservatives and should not be used if more than 4 hours have elapsed since the vial or container was first entered.37,135,139,204,205,206,207,208,210,211,212,213,214,215

Albumin human solutions may be used in conjunction with whole blood or plasma, or with dextrose, sodium lactate, or sodium chloride injections.135,204,205,206,207,208,210,211,212,213,214,215 However, albumin human solutions should not be mixed with parenteral nutrient solutions,257 protein hydrolysates,204,205,206,208,210,212,213,214,215 amino acid solutions,204,205,213,214 or solutions containing alcohol204,205,206,208,210,212,213,214,215 since protein precipitates may occur.206,212,213

When albumin human 25% is diluted with 0.9% sodium chloride injection or 5% dextrose injection, resulting 5% dilutions are approximately isotonic and iso-oncotic with citrated plasma; therefore, these diluents are preferred for such dilutions.133,136,137,204,205,208 Sterile water for injection must not be used to dilute albumin human solutions.125,126,127,128,129,130,133,134,135,136,137,138,184,204,205,206,207,208,210,214,215,254,255,256 Depending on the relative proportions of albumin human and diluent, dilutions prepared with sterile water may be dangerously hypotonic, carrying the risk of life-threatening hemolysis, particularly if large volumes of markedly hypotonic dilutions are inadvertently administered.37,124,125,126,127,128,129,130,131,132,133,138,184,207 (See Oncotic, Osmotic, and Tonicity Considerations under Cautions: Precautions and Contraindications.) Sterile water is compatible with albumin human and can be a suitable diluent in non -clinical situations (e.g., for preparing dilutions to be used in in vitro laboratory procedures).128

There are conflicting reports of the compatibility of albumin human with other IV infusion fluids; specialized references should be consulted for specific compatibility information.135

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