Albumin

(BANM, rINNM)

💊 Chemical information

Albümin; Albúmina; Albumine; Albuminum.
ATC — B05AA01.
ATC Vet — QB05AA01; QV08DA01 (microspheres of human albumin).

Pharmacopoeias.

Many pharmacopoeias have monographs, including Eur. and US.

Ph. Eur. 6.2

(Human Albumin Solution; Albumini Humani Solutio). An aqueous solution of protein obtained from the plasma of healthy donors; the plasma is tested for the absence of hepatitis B surface antigen and antibodies against HIV-1 and HIV-2 and hepatitis C virus. It is prepared as a concentrated solution containing 15 to 25% of total protein or as an isotonic solution containing 3.5 to 5% of total protein; not less than 95% of the total protein is albumin. A suitable stabiliser, such as sodium octanoate or N-acetyltryptophan or a combination of the two, may be added but no antimicrobial preservative is added. It contains not more than 160 mmol of sodium per litre and not more than 200 micrograms of aluminium per litre. The solution is sterilised by filtration and distributed aseptically into containers which are sealed to prevent contamination and maintained at 59° to 61° for not less than 10 hours. Finally, the containers are incubated for not less than 14 days at 30° to 32° or for not less than 4 weeks at 20° to 25° and examined visually for signs of microbial contamination. It should be stored in a colourless glass container and protected from light. A clear, almost colourless, yellow, amber, or green slightly viscous liquid. A solution in sodium chloride 0.9% containing 1% protein has a pH of 6.7 to 7.3. The BP 2008 gives Albumin and Human Albumin as approved synonyms.

USP 31

(Albumin Human). A sterile, nonpyrogenic, preparation of serum albumin obtained by fractionating material (blood, plasma, serum, or placentas) from healthy human donors, the source material being tested for the absence of hepatitis B surface antigen. It is made by a process that yields a product that is safe for intravenous use. It contains 4, 5, 20, or 25% of serum albumin and not less than 96% of the total protein is albumin. It may contain sodium acetyltryptophanate with or without sodium caprylate as a stabilising agent; it contains no added antimicrobial agent. It contains 130 to 160 mmol of sodium per litre. It is a practically odourless, moderately viscous, clear, brownish fluid. It should be stored in airtight containers.

💊 Adverse Effects and Precautions

Adverse reactions to albumin infusion occur rarely and include nausea and vomiting, increased salivation, flushing, urticaria, hypotension, tachycardia, and febrile reactions. These effects usually respond to slowing or stopping the infusion. Allergic reactions, including severe anaphylactic shock, are possible. Rapid increases in circulatory volume can cause vascular overload, hypertension, haemodilution, and pulmonary oedema. Solutions containing albumin 20 or 25% are hyperosmotic and draw fluid from the extravascular compartment. Infusion of albumin solutions is contra-indicated in patients with severe anaemia or heart failure. They should be given with caution to patients with hypertension or low cardiac reserve. Dehydrated patients may require additional fluids. Injured or postoperative patients should be observed carefully when given albumin as the rise in blood pressure may result in bleeding from previously undetected sites. Human albumin preparations carry a risk of viral transmission. Manufacturing processes, including heating to about 60°, have reduced the risk of transmitting some viral infections.

Aluminium toxicity.

Albumin solutions may contain appreciable amounts of aluminium. Marked increases in plasma-aluminium concentrations have been demonstrated in patients receiving large volumes by infusion and accumulation of aluminium may occur in patients with renal impairment.1-3 In the UK albumin solutions with an aluminium content of less than 200 micrograms/litre are available for use in premature infants and patients undergoing dialysis.
1. Milliner DS, et al. Inadvertent aluminum administration during plasma exchange due to aluminum contamination of albuminreplacement solutions. N Engl J Med 1985; 312: 165–7
2. Maher ER, et al. Accumulation of aluminium in chronic renal failure due to administration of albumin replacement solutions. BMJ 1986; 292: 306
3. Maharaj D, et al. Aluminium bone disease in patients receiving plasma exchange with contaminated albumin. BMJ 1987; 295: 693–6.

Critically ill patients.

Volume expansion with albumin (a colloid) has been widely used in critically ill patients, although its use had never been formally tested in large controlled studies. A systematic review based on available studies up to March 1998 (relatively small, old trials that recorded only a small number of deaths) suggested that albumin was of no benefit in critically ill patients with hypovolaemia, burns, or hypoalbuminaemia, and that it might be linked to increased mortality.1 The authors of the review stressed that these results should be treated with caution but nevertheless called for an urgent reconsideration of the use of albumin in critically ill patients. The review was severely criticised2 and while it was recognised that albumin had probably been overused in the past it was considered that more studies were required to define the effect of albumin on mortality.3-5 Another review6 found that the use of albumin did not significantly affect mortality; this meta-analysis had broader criteria and included studies that were considered to be relevant but that had been excluded by the other review. In response to this debate, albumin 4% was compared with sodium chloride 0.9% for resuscitation in a study of 6997 hypovolaemic patients in intensive care (the SAFE study).7 This large, randomised, double-blind study found equivalent rates of death from any cause during the 28-day study period. Survival-time during the 28 days, length of stay in the intensive care unit and in hospital, time on mechanical inhalation or renal replacement therapy, and development of organ failure were also similar. Although these two fluids seem clinically equivalent in a heterogeneous population of patients in intensive care, further study of selected groups, such as those with trauma or severe sepsis, is required. An update to the original 1998 review included the results of SAFE. The authors maintained that patients with burns (a group excluded from the large trial) or hypoproteinaemia might still be at risk of increased mortality, and although no longer suggesting a generally increased risk, concluded that there was no evidence that albumin reduced mortality in patients with hypovolaemia. Whether highly selected groups of critically ill patients might benefit is as yet unclear.8 Pharmacovigilance data reported to albumin suppliers over 3 years (1998 to 2000) has also been analysed.9 During this period of heightened awareness about possible adverse effects of albumin, due to the publication of the 1998 review, a total of 1.62 × 107 doses of 40 g had been distributed. Serious adverse effects possibly or probably related to albumin were found to be rare, and no death was classified as probably related to albumin use. On a broader level, debate continues about the relative merits and risks of such colloid solutions, compared with those of crystalloids such as glucose or sodium chloride solutions, in the management of hypovolaemia and shock.
1. Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. BMJ 1998; 317: 235–40
2. Various. Human albumin administration in critically ill patients. BMJ 1998; 317: 882–6. [Letters.
3. Tomlin M. Albumin usage in the critically ill. Pharm J 1998; 261: 193
4. McClelland B. Albumin: don’t confuse us with the facts. BMJ 1998; 317: 829–30
5. Committee on Safety of Medicines/Medicines Control Agency. The safety of human albumin. Current Problems 1999; 25: 11. Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=GET_ FILE&dDocName=CON2023234&RevisionSelectionMethod= LatestReleased (accessed 08/06/06
6. Wilkes MM, Navickis RJ. Patient survival after human albumin administration: a meta-analysis of randomized, controlled trials. Ann Intern Med 2001; 135: 149–64
7. The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350: 2247–56
8. The Albumin Reviewers. Human albumin solution for resuscitation and volume expansion in critically ill patients. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2004 (accessed 27/10/05)
9. Vincent J-L, et al. Safety of human albumin—serious adverse events reported worldwide in 1998–2000. Br J Anaesth 2003; 91: 625–30.

Dilution.

If concentrated albumin solutions are to be diluted before use, a suitable solution such as sodium chloride 0.9% or glucose 5% must be used. Albumin 25% that was erroneously diluted with water to produce a hypo-osmolar albumin 5% solution has produced severe haemolysis and renal failure in patients undergoing plasmapheresis,1,2 including a fatality in one patient.3
1. Steinmuller DR. A dangerous error in the dilution of 25 percent albumin. N Engl J Med 1998; 338: 1226
2. Pierce LR, et al. Hemolysis and renal failure associated with use of sterile water for injection to dilute 25% human albumin solution. Am J Health-Syst Pharm 1998; 55: 1057,1062, 1070
3. Anonymous. Hemolysis associated with 25% human albumin diluted with sterile water—United States, 1994–1998. MMWR 1999; 48: 157–9.

Transmission of infections.

There has been concern that albumin preparations may carry a potential risk of transmission of viral and subviral particles, notably Creutzfeldt-Jakob disease. In 1993, Pasteur-Mérieux (one of the largest producers of blood products) withdrew all products containing albumin derived from placental blood1 due to uncertainty regarding the adequacy of screening procedures for placentas as a source. It was considered that the agent responsible for Creutzfeldt-Jakob disease might be contained in placentas from women who have been treated with growth hormone derived from cadaver pituitaries. More recently, the production of blood products (including albumin) using plasma from UK donors has been phased out due to the possible risk of transmission of new variant Creutzfeldt-Jakob disease.
1. Anonymous. Placental-derived albumin preparations withdrawn. WHO Drug Inf 1994; 8: 29–30.

💊 Uses and Administration

Albumin is the major protein involved in maintaining colloid osmotic pressure in the blood. It also binds a number of endogenous and exogenous substances including bilirubin, steroid hormones, and many, mainly acidic, drugs. Albumin solutions are used for plasma volume replacement and to restore colloid osmotic pressure. They have been used in conditions such as burns, severe acute albumin loss, and acute hypovolaemic shock. They are also used as an exchange fluid in therapeutic plasmapheresis. Concentrated albumin solutions are used in neonatal hyperbilirubinaemia associated with haemolytic disease of the newborn. They have also been suggested for short-term management of hypoproteinaemia in hepatic disease and in diuretic-resistant patients with nephrotic syndrome but are of little value in chronic hypoproteinaemias. Albumin may be included in diagnostic preparations such as those labelled with technetium-99m for use as radiopharmaceuticals in scanning of the heart, lung, liver, spleen, bone marrow, veins, and lymphatic system. Albumin labelled with iodine-125 is used to measure blood and plasma volumes, blood circulation, and cardiac output. A suspension of albumin microspheres with perflutren is available for enhancing cardiac ultrasound imaging. Recombinant forms of human albumin have been developed as excipients for vaccines and other drug products, and for the treatment of hypoalbuminaemia and hypovolaemic shock. Albumin solutions are usually available as 4.5% or 5% solutions, which are iso-osmotic with plasma, and as 20% or 25% solutions which are hyperosmotic with respect to plasma, and cause a movement of fluid from the extravascular to the intravascular compartment. These concentrated solutions may be used undiluted or may be diluted with a suitable solution, commonly sodium chloride 0.9% or glucose 5%. Adequate hydration should be maintained and electrolytes monitored in patients receiving hyperosmotic solutions of albumin. The amount of albumin solution given will depend upon the clinical condition of the patient and the response to treatment. The following doses have been suggested:
acute hypovolaemic shock: an initial dose of 25 g for adults (for example, 500 mL of a 5% solution or 100 mL of a 25% solution) and up to about 1 g/kg for children
hypoproteinaemia: a maximum of 2 g/kg daily
neonatal hyperbilirubinaemia: 1 g/kg before exchange transfusion The rate of infusion should be adjusted according to the indication and patient response, but in general, suggested rates of infusion are up to 5 mL/minute (5% solution) or 1 to 2 mL/minute (20% solution). In plasmapheresis the albumin infusion rate should be adjusted according to the rate of removal. Albumin solutions should not be used for parenteral nutrition.
1. Nicholson JP, et al. The role of albumin in critical illness. Br J Anaesth 2000; 85: 599–610
2. Matejtschuk P, et al. Production of human albumin solution: a continually developing colloid. Br J Anaesth 2000; 85: 887–95
3. Haynes GR, et al. Albumin administration–what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol 2003; 20: 771–93
4. Mendez CM, et al. Albumin therapy in clinical practice. Nutr Clin Pract 2005; 20: 314–20
5. McLeod BC. Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange. Best Pract Res Clin Haematol 2006; 19: 157–67
6. Kobayashi K. Summary of recombinant human serum albumin development. Biologicals 2006; 34: 55–9.

💊 Preparations

Ph. Eur.: Human Albumin Solution; USP 31: Albumin Human.

Proprietary Preparations

Arg.: Buminate; Zenalb†; Austral.: Albumex; Austria: Albuminativ; Braz.: Albumax†; Albuminar; Beribumin; Blaubimax; Blaubumin†; Plasbumin; Zenalb†; Canad.: Plasbumin; Chile: Plasbumin; Cz.: Flexbumin; Denm.: Octalbin; Fin.: Albuminativ; Octalbin; Fr.: Octalbine; Vialebex; Ger.: Humanalbin; Gr.: Zenalb; Hong Kong: Albuminar; Albutein; Biseko; Buminate; Kamapharm; Plasbumin; Indon.: Albapure; Alburaas; Albutein; Farmin; Fimalbumin; Octalbin; Plasbumin; Israel: Albuminar; Egg Plus; Plasbumin†; Ital.: Albital; Albuman†; Alburex; Albutein; Plasbumin; Jpn: Medway; Malaysia: Albutein; Buminate; Plasbumin†; Zenalb; Mex.: Albital†; Albumar†; Albumyn†; Biomina†; Buminate†; Hi-Bumin†; Octalbin; Probialbumin†; Seralbumin†; Vanderbumin; Neth.: Albuminativ†; Cealb; Octalbine; NZ: Albumex; Philipp.: Albumax; Albuminar; Albutein; Plasbumin; Pol.: Biseko; Port.: Flexbumin; Rus.: Plasbumin (Плазбумин); S.Afr.: Albusol; Singapore: Albutein; Plasbumin†; Zenalb; Spain: Octalbin; Plasbumin; Swed.: Albuminativ; Switz.: Albuman; Thai.: Alburaas; Albutein; Buminate; Zenalb; Turk.: Alba; Albuman; Albuminar; Cealb; Plasbumin; Zenalb; UK: Alba†; Albutein; Zenalb; USA: Albumarc; Albuminar; Albutein; Buminate; Plasbumin. Multi-ingredient: Denm.: Pharmalgen Albumin; Swed.: Tisseel Duo Quick.
Published October 09, 2018.