HES: review of pharmacokinetics, dynamics, current products, etc. JVECC 2014 Flashcards
What is HES synthesized from?
amylopectin
- natural starch derived from corn/potatoes
What are the 3 numbers provided by the HES manufacturer?
average molecular weight (MW)
molecular substitution (MS)
pattern of substitution (C2/C6 ratio)
What are the names of HES with molecular substitutions of 0.4, 0.5, 0.6, or 0.7?
- tetrastarch
- pentastarch
- hexastarch
- hetastarch
What is the molecular weight of albumin in dogs?
64-67 kDa
What do these numbers represent?
Name the modified Starling’s equation
Jv = Kf (HPc - HPi) - ohm (COPc - COPg)
JV = net fluid movement across the capillary
Kf = filtration coefficient
Why was 6% hetastarch formerly labeled with a lower molecular weight average?
because the weight could be determined more accurately with a newer method (low-angle laser light scattering)
previous method: chromatography
What is the glomerular molecular weight filtration threshold?
45-60 kDa
If HES molecules’ size is above the glomerular filtration threshold
alpha-amylase breaks larger molecules down –> until small enough to be filtered through the glomerulus
What determines how long HES remain in the intravascular space? (MW, MS or C2/C6 ratio)
all
- larger molecules –> must be broken down into smaller parts before excretion
- higher molar substitution –> higher number of sites of substitution (e.g., hetastart compared to hexastarch) –> reduces access of alpha-amylase to the intermoleculalr bonds for degradation
- higher C2/C6 ratio –> HE groups positioned on the C2 atom block alpha-amylase more effectively
What characteristic of HES are the most important for determining pharmacokinetics?
molar substitution and pattern of substitution
Do dogs or people eliminate HES faster?
dogs - shorter half-life because of higher plasma alpha-amylase concentration
What are the mechanisms of HES elimination?
- renal - 70% (the smaller the molecule the faster, because of glomerular filtration)
- transient storage in the reticuloendothelial cells of liver, spleen, lymph nodes, IV and interstitial spaces (increased tissue storafe with increased molar substitution
- bile excretion
List 5 reported side effects of HES administration (including in people)
- volume overload
- coagulopathies
- AKI
- proinflammatory effects
- allergic reactions
What are the presumed mechanisms of AKI from HES administration?
- HES macromolecule reabsorbtion into proximal renal tubular cells –> osmotic nephrosis (vacuolization and swelling of cells)
- hyperoncotic AKI, i.e., increased intravascular COP reduces glomerular filtration
- backleak of filtrate across damaged tubular epithelium
- dilutional hypoalbuminemia - decreased levels of renoprotective albumin
According to a recent Cochrane review, what subcategory of critically ill patients is at a higher risk of AKI from HES administration?
Sepstic patients
After administering HES to dogs, what changes may occur on the urine analysis?
increased specific gravity - no changes to osmolality
List 4 coagulation abnormalities reported with HES administration
- platelet dysfunction (decreased adhesion)
- decreased vWF
- decreased FVIII
- hyperfibrinolysis
How does HES affect platelets?
HES molecules bind to platelet bindings sites (not the fibrinogen one)
How do coagulopathic effects of tetrastarch and hetastarch differ?
tetrastarch
* less PLT inhibition
* less vWF-VIII binding (because excreted faster)
* more hyperfibrinolysis
How does tetrastarch increased fibrinolysis?
disrupts the thrombin-TAFI relationship
What is the initial expansion volume of 450 mL of 6% Hetastarch in healthy normovolemic patients at time 0 and 30 min?
450 min time 0
>650 mL 30 min later
How did the initial and delayed plasma expansion compare between 0.9% NaCl and HES in Silverstein et al?
0.9% NaCl caused more plasma volume expansion initially but fell below HES 30 min later
What is the normal Colloid osmotic pressure in healthy dogs?
17.5 - 22.7 mm Hg
What is the reported colloid osmotic range in hypoalbuminemic dogs?
5.8 - 12.7 mm Hg
What are the two theories of how HES administration helps with capillarby hyperpermeability?
- plugging intercellular gaps
- immunomodulators
