ALBUMIN
Indications and clinical benefits
The package inserts of albumin solutions for restoration and maintenance of circulating blood volume and volume deficiency in Europe follow the SPCs developed by the EMA and endorsed by the national health authorities that came into effect on 1 February 2019
Christian Wiedermann MD FACP Research Associate , University of Health Sciences , Medical Informatics and Technology Hall in Tyrol , Austria ; Professor of Internal Medicine , Medical University of Innsbruck , Austria
Albumin is the most abundant plasma protein in the human body , alone constituting about 55 % of the total protein content of plasma . lt comprises a single polypeptide chain of 585 amino acids with a molecular weight of 66,500 Daltons , and is synthesised entirely by the liver . Of the total content of albumin ( about 250 – 350g for a healthy 70kg adult ), approximately 40 % is located in the intravascular compartment , and its half-life is about 20 days . 1
Albumin is a multi-functional protein with both colloidal and pharmacological activity . The exchange of fluids between the intravascular and extravascular compartments is basically governed by the levels of hydrostatic and oncotic pressure and the degree of capillary membrane permeability . Albumin ‘ s colloidal activity is essential in maintaining fluid balance between the intravascular and interstitial compartments . Because it is the predominant plasma protein , albumin accounts for approximately 75 – 80 % of plasma colloid osmotic pressure ( COP ). Due to the presence of several histidine residues with an acid dissociation constant very similar to the plasma pH , albumin is an excellent buffer in plasma as well as the main extravascular buffer able to donate positive and negative charges in case of alkalosis and acidosis , respectively ( see Table 1 ). In addition , albumin is endowed with diverse biologically specific capabilities such as ligand binding , antioxidant , free radical-scavenging and anti-inflammatory activity , inhibition of apoptosis and cell signalling . 1
Albumin specifically binds to a wide array of endogenous ligands , including metabolites , lipids , hormones , metal ions and high-affinity endothelial cell albumin receptors . 2 Ligand binding itself may serve multiple purposes such as transport ,
TABLE 1
The main physiological functions of albumin
• Regulation of oncotic pressure of the plasma
• Regulation of the acid – base balance
• Binding , transport and metabolism of organic compounds , metabolic degradation products , drugs and protection from exogenous toxins
• Effects on haemostasis
• Integrity of the microcirculation and capillary permeability
• Antioxidant reserves and extracellular sulfhydryl groups sequestration and transcytosis . Additionally , albumin binds numerous administered drugs and in many cases can modify their bioavailability and pharmacokinetics . 3 For example , albumin administration results in increased effects of loop diuretics by augmenting drug delivery to the renal tubule . 4 Evidence concerning these non-oncotic pharmacological properties of albumin continues to accumulate rapidly . Albumin plays a modulating role in haemostasis due to binding between sulfhydryl groups of albumin and nitric oxide ( NO ), thus slowing the inactivation of NO , which exhibits anti-aggregating effects on platelets and has vasodilator properties . 5 Albumin contributes to the maintenance of normal permeability of capillaries to macromolecules and solutes and restricts the increase in the course of inflammation . This function is due to the presence of albumin within the capillary wall and might be directly derived both from its high negative charge , resulting in electrostatic repulsion of negatively charged molecules , and from space-occupying effects . 6 Indirect action on the microcirculation could be mediated by binding with arachidonic acid , a molecule that increases capillary permeability . Furthermore , albumin inhibits the adhesion of human neutrophils to endothelial cells . 7
Fluid therapy In general , fluid therapy is used for replenishing fluid losses , to restore effective circulation as well as to correct acid-base and electrolyte disturbances . This is accomplished with two categories of substance : crystalloid and colloids . The crystalloid solutions distribute easily into the extracellular space , are used for maintenance as well as replacement of blood volume and serve as a vehicle for drug delivery . Crystalloids should have a composition similar to extracellular fluid . A disadvantage is that they have a short duration of action . Colloids are solutions that contain larger and heavier molecules , which procure an increase in COP and are able to increase the volume of plasma by attracting water from the extracellular spaces . Colloids in clinical use are classified as natural ( plasma and human albumin ) or artificial or semi-synthetic solutions . The individual coiloids differ in their abilities to expand plasma volume depending on the COP of each fluid . Human albumin solutions are available both at low ( 4 %, 5 %) and high concentrations ( 20 %, 25 %) and exert a COP of about 20 and 70 mmHg , respectively , the latter being the highest COP solution available . Synthetic colloids have been proposed as an alternative to crystalloids but they may have serious side effects .
12 | 2019 | hospitalpharmacyeurope . com