Albumin is the most abundant protein in the blood and accounts for about 50% of all plasma proteins. It gets synthesized by the liver and secreted immediately without storage. The physiological regulators of albumin are the colloid osmotic pressure and nutritional status. The metabolism of albumin depends on the synthesis, distribution over interstitium and intravascular compartment, and excretion. Normal blood plasma concentration is between 3.5 to 5 g/dL, and 60% of the total albumin is in the interstitial space.[1][2] The mean half-life is about 28 to 36 days.[3]

The chief medical uses are pharmacological therapy, serum marker to monitor diseases, biomaterials, and vaccines.

FDA-Approved Indications

• Hypovolemia with or without shock: During fluid resuscitation in patients with hypovolemia, intravenous albumin is suggested as a second-line therapy if there is an inadequate response to crystalloids. In critical-ill patients, the survival rate at 90 days showed no significant difference when treated with albumin or crystalloids as first-line therapy (RR 0.98; 95% CI, 0.92-1.04).[4] Albumin group had more free days of ventilation and vasopressor therapy than the crystalloid group (mean difference 1.10 and 1.04, respectively).[5] The recommended dosage is 500 ml of albumin 5% and repeats every 30 minutes if necessary.
• Prevention of central volume depletion after paracentesis due to cirrhotic ascites: In a study by Runyon et al., albumin infusion has shown to improve cardiovascular function after large-volume paracentesis (over 5 liters) in patients with cirrhosis and tense ascites. [6] A meta-analysis by Bernardi et al. reported an overall decrease in mortality (OR 0.64; 95% CI, 0.41-0.98).[7] It also prevents hyponatremia, the elevation of BUN, aldosterone, and renin.[8] The recommended dosage is one dose of albumin 25%, 5 to 10 g/L of ascites, for more than 5 liters fluid drained.[7] When ascites drainage volume is less than 5 liters albumin infusion lack of benefit, however,  based on consensus more than facts, the International Ascites Club recommends the use of plasma expanders for less than 5 L fluid drained.[9][10]
• Hypoalbuminemia is a common clinical finding in critically ill patients, malnutrition, and other diseases. The mainstay of therapy is to treat the underlying cause. Data are insufficient to recommend albumin in hypoalbuminemia patients. In a few cases, albumin 25% can be used to relieve symptoms due to hypoalbuminemia, but there is a high risk of fluid overload. One meta-analysis evaluated mortality as an outcome in hypoalbuminemia patients receiving Albumin infusions. They concluded that there was no significant effect on mortality if hypoalbuminemia was corrected, relative risk 1.59 (0.91–2.78).[11] A clinical trial by Dubois et al. evaluated the effect of albumin infusion in organ function in critically ill patients with hypoalbuminemia. They reported an improvement in organ function and a higher caloric intake in those who received albumin versus placebo.[12] Supplementation of albumin to malnourished patients with hypoalbuminemia is not a recommended therapy.[13]
• Ovarian hyperstimulation syndrome is a serious complication of assisted reproduction technologies, leading to an increase in vascular permeability and a shift of intravascular volume into the third space. It can cause thromboembolic events or ischemia. Albumin 25% is indicated as a plasma volume expansion in addition to crystalloids (Grade C recommendation). Studies have not shown strong evidence of its efficacy.[14] Dosage recommended: 15 to 20 mL/hr for 4 hours.[15] Albumin administration is not indicated to prevent ovarian hyperstimulation syndrome.[16]
• Acute Respiratory Distress Syndrome (ARDS): It is used with loop diuretics in the treatment of ARDS when pulmonary overload and hypoalbuminemia are present. A small clinical trial demonstrated improvement in oxygenation, total fluid balance, and hemodynamic function in patients who received albumin plus furosemide versus those with furosemide only, resulting in a reduction of organ failure.[17] The recommended dosage is albumin 25 g plus furosemide over 30 minutes that may be repeated every 8 hours for up to 3 days.There is no improvement in long term outcome of critically ill patients like mortality or Ventilator free days.[18]
• Acute nephrosis: This recommendation has, as its basis, a review article from 1977. Indicated to treat edema in patients with nephrotic syndrome refractory to cyclophosphamide and corticosteroids. Such cases may respond with loop diuretics and 100 mL of albumin 25% solution daily for 7 to 10 days.[19] Newer small clinical trials have shown a good resolution of edema with loop diuretics and albumin infusion vs. diuretics alone in children with nephrotic syndrome. Despite low samples, there was a statistical difference.[20][21]
• Hemolytic disease of the newborn: Albumin is indicated as an adjunct therapy to treat neonatal hyperbilirubinemia during exchange transfusions. The efficacy is believed due to its ability to bind unconjugated bilirubin. The recommended dose is 1 g/kg per dose of albumin 25% during the exchange transfusion.[22] A significant difference in the reduction of total bilirubin levels at 6 and 12 hours was seen in patients treated with albumin 1 hour before exchange transfusion versus those with only exchange transfusion (p < 0.001).[23] The combined use of albumin with phototherapy is not indicated because it may cause detrimental effects.[24]
• Burn hypovolemia: Previously, albumin infusion was recommended in conjunction with crystalloids 24 hours after thermal injury if burns had covered more than 50% of the body surface or crystalloid therapy has failed.[22] The current recommendation suggests it may be useful in terms of decreasing fluid volume requirements. A recent meta-analysis showed that albumin solutions for acute resuscitation in burn-injured patients have no benefit on mortality (RR 1.6; 95% CI, 0.63 to 4.08) but the total volume used during resuscitation was less (RR -1; 95% CI, -1.42 to 0.48) compared to non-albumin solutions.[25]
• Extensive hemodialysis: About 20% to 55% of patients on hemodialysis develop hypotension during their hemodialysis session. High rate or excessive volume ultrafiltration are the main causes. Albumin 5% is used as second-line therapy when hypotension does not respond to crystalloids.[26] One study compared the use of albumin versus crystalloids in hypotension during hemodialysis. The results showed no significant differences in the main and secondary outcomes, the achievement of the ultrafiltration volume target, and time to restore blood pressure or treatment failure, respectively.[27]
• Cardiopulmonary bypass: Albumin is useful as a colloid for priming extracorporeal circuit and for volume expansion in cardiopulmonary bypass. These recommendations have their basis in a study by Wilkes that showed a reduction of acute postoperative mediastinal hemorrhage after cardiopulmonary bypass in patients exposed to albumin solutions compared to another colloid.[28] Moreover, another study reported a favorable result in the preservation of platelet counts and maintaining the colloid osmotic pressure during cardiopulmonary bypass compared to crystalloids.[29]

Non-FDA-Approved Indications

• Spontaneous bacterial peritonitis (SBP) is a significant cause of mortality in cirrhotic patients. Administration of albumin 1.5 g/kg within 6 hours and 1 g/kg on day three along with antibiotics have a better effect in preventing renal impairment and reducing mortality from 29% to 10% in cirrhotic patients with SBP compared to those receiving antibiotics only.[30] Another clinical trial confirmed the benefit of this therapy with laboratory, cardiac, and Doppler parameters. Improvement in portal vein flow volume (p = 0.01) and reduction of inflammatory marker TNFa in ascites (p = 0.04) were reported.[31]
• Albumin as Marker of Preoperative nutrition status and postoperative outcome in elderly general surgery patients-Serum albumin is the most used preoperative nutrition parameter. Low serum albumin was a significant preoperative predictor of postoperative complications and postoperative mortality. Low serum albumin predicted the prolonged length of stay in the hospital. Serum albumin can be a reliable predictor of postoperative outcome in elderly general surgery patients.It is questionable whether serum albumin is a good representative of nutrition status. In general, it is advocated that serum albumin should not be seen as a nutrition parameter but rather as a "marker of inflammatory metabolism". Serum albumin might be used to identify the sickest patients, who, as a consequence, are also at risk for nutrition deterioration.Weight loss in the previous 6 months might be an indicator of postoperative outcome, but the current evidence is not very strong.[32]
• Albumin Dialysis (Molecular adsorbent recirculating system also called as MARS) has been used as an extracorporeal liver replacement device for the treatment of Acute Liver failure secondary to toxin ingestion, trauma or as a bridge to transplantation for massive hepatic necrosis.[33]

The regular price of intravenous albumin solution is around $0.5 to $6 per milliliter. Compared to saline solutions $0.01 to $0.1 per milliliter, albumin solutions are 60-times more expensive. Price takes place when saline solutions and albumin infusions have the same efficacy in the treatment of a disease.

Albumin has two essential physiologic functions[2]: 

• Contribute to colloid osmotic pressure
• Aid in the transport, distribution, and metabolism of endogenous and exogenous molecules (fatty acids, thyroid hormones, metals, oxide nitric, peptides, and drugs)

The principal mechanism of action of albumin infusion is to increase the colloid osmotic pressure. It drives the interstitial fluid into the intravascular compartment and increases the effective volume of the circulatory system.[3]

The only mode of administration of albumin is by intravenous (IV) infusion. There are two formulations available that differ on the albumin concentration; albumin 5% and 25%. In general terms, albumin 25% is the therapeutic choice when either sodium or fluid is restricted or in cases of oncotic deficiencies. Albumin 5% use is more common in situations of volume loss as dehydration. However, concentration, the rate of infusion, and dosage depend on the clinical situation, as stated above.

Since albumin solution is a human-derived blood product, adverse effects are rare. In less than 0.1%, anaphylactoid reactions, flushing, urticaria, fever, chills, nausea, vomiting, tachycardia, and hypotension can occur. These reactions normally disappear when the infusion rate is slowed or stopped. Edema and fluid overload are common adverse effects, which depend on the volume, speed of the infusion, and the clinical scenario. In very rare cases, anaphylactic shock may occur. (Pharmaceutical prescribing information).

• Hypersensitivity to any component in albumin preparations or excipients is a contraindication.
• Contraindications include clinical situations that present with volume overload, for example, severe anemia, congestive heart failure, or renal insufficiency, are at high risk of hemodynamic instability when treated with albumin solutions.
• Do not dilute any albumin solution with sterile water because it may cause hemolysis and acute kidney injury (AKI) in the recipient.[34] (Pregnancy Category C).