Anticoagulation with nadroparin in continuous venovenous hemofiltration (CVVH): extracorporeal clearance and systemic effects of nadroparin

The low molecular weight heparin nadroparin is standard anticoagulation for
continuous venovenous hemofiltration (CVVH) in many intensive care units in the
Netherlands. The drug is administered intravenously in a fixed dose without
monitoring of anti-Xa acitivity. The drug is excreted by the kidneys for about
10%. Studies indicate that nadroparin acculmulates in renal insufficiency,
increasing the risk of bleeding. While older studies indicate that low
molecular weight heparins are not excreted with hemofiltration, a recent small
study shows that extracorporeal clearance of the low molecular weight heparin
enoxaparin is comparable to normal total plasma clearance.

Aim of the present study is to determine
· whether and to what extent nadroparin is excreted by CVVH
· whether the drug accumulates during CVVH as measured by anti-Xa activity and
endogenous thrombine potential (ETP)
· whether clearance of nadroparin is related to the dose of CVVH
· the relation between anti-Xa activity and ETP in plasma

Patients are randomized for CVVH at a rate of 2 L/h or CVVH at a rate of 4 L/h.
After one hour, CVVH dose is converted to 4 L/h or 2 L/h respectively. Blood
and ultrafiltrate is sampled according to the protocol.

There is no risk for the patient. Both modes of CVVH (2 L/h or 4 L/h) are
standard treatment. Burden: a total volume of 50 ml of blood is sampled. Blood
is sampled form the arterial line and from the CVVH circuit which are both in
situ for standard treatment.