Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c20 CUFX213A/Peck 9780521618168 December 28, 2007 14:10

20 Intravenous fluids

ischaemia and ultimately renal failure. This hyperoncotic acute renal failure is

particularly likely in the severely dehydrated patient who receives large volumes

of colloid.


Accumulation–the reticuloendothelial system takes up HES and stores it. The

degree of substitution and the total dose administered are the determining factors.

Ithas been reported that following administration of large doses of HES, patients

occur an itch, which may develop weeks later.


Anaphylaxis–the incidence is in the order of 1 in 20 000.

Hydroxyethyl starch is clearly a very heterogenious group. Some of the older products

have been associated with significant problems, but there is hope that the newer

medium molecular weight products in balanced preperations may provide fewer

problems.

Albumin

Albumin accounts for∼50% of the 5 available plasma proteins, the other 50% com-

prisingα1-,α2-,βglobulin andγglobulin. It is made up of 585 amino acids, has a

molecular weight of 69 000 Da and is folded into a series ofαhelices, which form 3

domains each with a hydrophobic core and a polar outer exterior.

Hypoalbuminaemia in the critically ill has traditionally been corrected with infu-

sions of albumin. However its use has become less widespread following work that

showed no benefit over other colloids. Further research is required to clarify the

situation.

Functions

Albumin exerts a greater colloid osmotic effect than its molecular weight alone might

suggest due to its highly negative charge.

Albumin binds and transports drugs and endogenous molecules in the plasma.

Acidic drugs (warfarin, aspirin, furosemide and amiodarone) tend to bind to albumin

while basic drugs bind toα1- acid glycoprotein. Reductions in albumin concentration

can increase the effects of drugs such as warfarin by increasing the free fraction.

Albumin carries bilirubin, fatty acids, calcium and magnesium. Despite a low binding

affinity, a significant amount of steroid is carried by albumin due to its abundance.

Kinetics

Albumin is synthesized in the liver and has a half-life of 20 days. Just under 50% is

intravascular the remainder being present in the skin and muscle with lesser amounts

in the gut, liver and subcutaneous tissue. In health albumin synthesis is balanced

to match metabolism. Where metabolism or loss (renal or gastrointestinal) are sig-

nificantly increased synthesis may not be able to keep up and hypoalbuminaemia

ensues.