Population PK/PD of propofol and nadroparin in extreme morbidly obese patients

There is an increasing incidence of obese patients in Western countries of 20%
in men and 25% in women in the United States, respectively. As studies on the
influence of (morbid) obesity on the pharmacokinetics and pharmacodynamics of
commonly used drugs are scattered, there is a need for systematic
pharmacokinetic and pharmacodynamic studies in this special group of patients.
Therefore we recently evaluated the pharmacokinetics and pharmacokinetics of
both propofol and nadroparin in morbidly obese patients (POP study (VCMO
registration number R-06.42A) and POP-2 study (VCMO registration number
R-09.13A)). For propofol, a pharmacokinetic and pharmacodynamic model based
dosage regimen in morbidly obese patients up to a total body weight of 170 kg
was developed. This dosage regimen is nowadays common practice for anaesthesia
of morbidly obese patients up to total body weight of 170 kg in our hospital.
For nadroparin, a pharmacodynamic model was developed using anti-Xa levels. The
results of this analysis showed similar clearance values in patients with a
total body weight lower than 170 kg while in three patients with a total body
weight higher than 170 kg, increased clearance values were observed.

This study is performed in order to study the population pharmacokinetics and
pharmacodynamics of propofol and nadroparin in morbidly obese patients with a
total body weight higher than 170 kg. The recently developed and published
pharmacokinetic and pharmacodynamic models will serve as a basis and a
covariate analysis will be performed on all available data in order to account
for variability in pharmacokinetic and/or pharmacodynamic parameters.

A therapeutic and non-invasive study.

A maximum amount of 50 millilitres of blood will be sampled from an indwelling
arterial line during and after surgery. The patient will be asked to count
slowly during induction of anaesthesia. The arterial line will be kept in place
4 hours longer than usual. One week after surgery the patient will be checked
for thrombosis using ultrasonography. During surgery cardiac output will be
measured using two different monitoring systems, the NICOM® (Cheetah Medical)
and Vigileo (Edwards Lifesciences). These non-invasive cardiac output
measurements do not represent additional burden of the patient.