Steroid-induced reduction of surgical stress

The stress response as induced by myocardial cellular damage during cardiac
surgery may lead to myocardial stunning and apoptosis, and could therefore
impair postoperative patient recovery. Surgical trauma typically induces the
liberation of cytokines. Some of these cytokines are strongly associated with
the initiation of intracellular proapoptotic pathways through activation of
tyrosine kinases and integrins. The latter are known for their deteriorating
effects on cardiac function and are strongly involved in cardiac remodeling.
Dexamethasone is typically administered prior to cardiac surgery in order to
especially reduce the release of proinflammatory cytokines. It has however
never been investigated whether this additionally reduces proapoptotic
signaling in the human heart, thereby eliminating risk factors for the
induction of cardiac dysfunction. In the present study, we therefore aim to
investigate whether dexamethasone inhibits proapoptotic pathways in patients
undergoing cardiac surgery. Furthermore, we would like to elucidate whether
this proposed effect of dexamethasone is related to the reduction of the stress
response in the heart or indirectly by suppression of cytokine release. For
this purpose we will obtain cardiac biopsies and plasma from patients, who are
randomly assigned to placebo or dexamethasone treatment and undergo on and
off-pump coronary artery bypass grafting (CABG) surgery.

Does dexamethason reduce the levels of plasma inflammatory proteins in patients
undergoing coronary artery bypass graft (CABG) surgery who have a normal or
disturbed ejection fraction such that proapoptotic pathways are inhibited?

Does a dexamethasone-induced alteration in plasma inflammatory markers lower
proapoptotic signaling in atrial biopsies of CABG patients?

Single-blinded, placebo controlled, randomized single center clinical trial.
The study will be performed in the VUmc.
Patients will be randomly assigned into two study groups:
(A) Placebo
(B) High dose of dexamethasone

In both the following patients will be included:
(a) Use of cardiopulmonary bypass (on-pump), ejection fraction > 50%
(b) Use of cardiopulmonary bypass (on-pump), ejection fraction < 50%
(c) No use of cardiopulmonary bypass (off-pump), ejection fraction > 50%
(d) No use of cardiopulmonary bypass (off-pump), ejection fraction < 50%

0.05 ml/kg dexamethason, i.v. (20 mg/ml, clear fluid) or placebo

Dexamethasone: By suppression of the inflammatory response by dexamethasone the
occurrence of postoperative infections and postoperative hyperglycemia is
slightly increased. These risks are however minimal. Moreover, the attending
anesthetist has the possibility to treat all possible complications and may
start any treatment that is necessary to guarantee an optimal patient health
condition.

Blood sampling from an intravenous catheter: Peripheral intravenous catheter
placement is standard perioperative procedure in all surgical patients, and
will therefore not add up to patient discomfort in the present study. Patients
with anemia will be excluded from the present study (Hb < 5 mmol/l).

Atrial biopsies: Atrial biopsies will be taken from the right atrial appendage
during on-pump surgery. Since part of the appendage will be removed for
cannulation of the right atrium, the biopsy will not increase patient risk.