To study the cardiovasculair effects of vasodilatation by nifedipine (Adalat gastrointestinal therapeutic system) with or without plasma volume expansion with Voluven (colloid) in women with preeclampsia

Nifedipine is a calciumantagonist used in obstetrics off-label as an
anti-hypertensive drug as well as for premature labour.
Despite its frequent use the hemodynamic effects in pregnancy are only
partially known.
In preeclampsia the maternal circulation is characterized by an increased
bloodpressure and an increased systemic vascular resistance, a decreased
cardiac output and a decreased circulating plasma volume. Correction of the
circulating volume by plasma volume expansion only, does not result in a
significant bloodpressure drop or other improvement of the maternal or foetal
condition.
Reduction of the arterial systemic resistance by nifedipine leads to a
substantial reduction of the bloodpressure en increase of the cardiac output.
An uncontrolled reduction of the bloodpressure can lead to uterine
hypoperfusion and foetal distress. The combination of both strategies, plasma
volume expansion together with vasodilatation by dihydralazine, has been used
succesfully for years. In the UMCN and other hospitals, nifedipine has been
used extensively as capsules as well as in the longacting GITS formulation.
However the pharmacodynamics of Adalat GITS have not been extensively studied
during pregnancy with or without plasma volume expansion. In view of the daily
use of Adalat GITS in pregnancy we think it is necessary to do so. Also there
is a lack of pharmacokinetic data on Adalat GITS think in pregnancy .

The first aim is to study the cardiovascular effects of nifedipine in pregnancy
in patients with preeclampsia.

Our second aim is to answer the following questions:
Does Adalat GITS with plasmavolume expansion in patients with preeclampsia,
lead significantly more often to a desired (ca 20%), controlled, reduction of
the peripheral vascular resistance (calculated from the mean arterial pressure
and the cardiac output) than without plasmavolume expansion?

Secundairy aims:
1. Does Adalat GITS with plasmavolume expansion in patients with preeclampsia
lead less often to a change in the doppler flow profiles of the uterina artery,
the variability of the foetal hartrhythm, as a sign of changed uterine
perfusion?
2. Characterization of the pharmocokinetics in patients with preeclampsia of
Adalat GITS with or without plasmavolume expansion?

Prospective randomised, unblinded study in pregnant women with preeclampsia in
whom vasodilatation is established by Adalat GITS with or without plasmavolume
expansion by 500 ml Voluven.

It is comparable with a routine hospital admission.
the extra burden consists mainly of the more frequent registration of the
bloodpressure, saturation and pulse. The bloodpressure will be measured
invasively via an intraarterial catheter. The cardiac output will be measured
with Innocor, an apparatus that uses the measurement of sulfahexafluoride, an
insoluble gas that is harmless, during inspiration and expiration, using the
Fick principle. The cardiovascular measurements will be performed 10 times at
2, 4, 6, 8, 12, 16, 24, 36, 48 hours.
There will be two additional ultrasound examinations apart from the routine
ultrasound examination.
Regarding the plasma volume measurement: routine intravenous excess; 20 cc of
dextraan 70 will be administered and at different times a serumsample will be
drawn from the arterial line at 10, 20 and 30 minutes. This test will be
repeated at 24 hours. At the protocol-times of (0), 2, 4, 8, 16, 24, 48 hours a
bloodsample will be taken for determination the nifedipine serumconcentration.
Instead of a cardiotocogram twice in 48 hours, an additional 8 ctg's will be
performed for 30 minutes each