Anticoagulation therapy advisor: a decision-support system for heparin therapy during ECMO.
We present a case study describing our development of a mathematical model to control a clinical parameter in a patient--in this case, the degree of anticoagulation during extracorporeal membrane oxygenation (ECMO) support. During ECMO therapy, an anticoagulant agent (heparin) is administered to prevent thrombosis. Under- or over-coagulation can have grave consequences. To improve control of anticoagulation, we developed a pharmacokinetic-pharmacodynamic (PK-PD) model that predicts activated clotting times (ACT) using the NONMEM program. We then integrated this model into a decision-support system, and validated it with an independent data set. The population model had a mean absolute error of prediction for ACT values of 33.5 seconds, with a mean bias in estimation of -14.3 seconds. Individualization of model-parameter estimates using nonlinear regression improved the absolute error prediction to 25.5 seconds, and lowered the mean bias to -3.1 seconds. The PK-PD model is coupled with software for heuristic interpretation of model results to provide a complete environment for the management of anticoagulation.
Peverini
R L
RL
Section on Medical Informatics, Stanford University, CA 94305-5479.
Sale
M
M
Rhine
W D
WD
Fagan
L M
LM
Lenert
L A
LA
D001778:Blood Coagulation Disorders / Q000209:etiology / Q000517:prevention & control*; D004360:Drug Therapy, Computer-Assisted; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000628:therapy; D008171:Lung Diseases / Q000151:congenital / Q000628:therapy; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D014914:Whole Blood Coagulation Time
D006493:Heparin