The effect on cerebral oxygenation of retrograde autologous priming of the CPB circuit in cardiac surgery patients: a Randomized Controlled Trial

In cardiac surgery, prolonged intraoperative cerebral desaturation is
associated with postoperative cognitive dysfunction (POCD) (1, 2),
characterised as impairment in attention, cognition, recognition, orientation,
memory and learning. It may result in prolonged hospitalisation, increased
morbidity and mortality, while it has an adverse impact on quality of life
after surgery.
We also know that cerebral perfusion during cardiopulmonary bypass (CPB) is
influenced by a numbers of factors, including hemodilution.
Retrograde autologous priming (RAP) is a technique where, the patient*s own
circulating blood partially replaces the priming solution in the CPB, which
results in less hemodilution and less transfused red blood cells compared to
the conventional CPB priming method in cardiac surgery patients. In their
retrospective study Hwang et al. assessed the regional cerebral oxygenation
(rSO2) by near-infrared spectroscopy (NIRS) and concluded that RAP limited the
degree of hemodilution and limits the deterioration in the rSO2 with a mean
difference of 5% points during CPB, compared to the conventional priming method
(4).
Different studies have shown a significant association between intraoperative
oxygen desaturation, assessed by rSO2 desaturation score, and POCD (1). Slater
et al. showed that patients with an rSO2 desaturation score50 > 3000 had a
significantly higher risk of postoperative cognitive decline (OR = 2.22, p
=0.024) (1). However, because of the absence of prospective studies, the effect
on regional cerebral oxygenation by RAP still remains unclear. We therefore
hypothesize that RAP limits the degree of hemodilution and thereby limits the
prolonged intraoperative cerebral desaturation, assessed by the incidence of
rSO2 desaturation score50 > 3000.

Primary Objective:
The primary objective of this study is to determine whether RAP limits the
degree of hemodilution and limits prolonged intraoperative cerebral
desaturation during during CPB, compared to the conventional priming method.
Prolonged intraoperative cerebral desaturation will be assessed by rSO2
desaturation score50. rSO2 desaturation score50 > 3000 is associated with
increased risk of cognitive decline (1). We hypothesize that RAP limits the
degree of hemodilution and thereby limits the incidence of rSO2 desaturation
score50 > 3000 with a relative difference of 50%. Formula described by Slater
et al. : rSO2 score = 50% rSO2 - current rSO2 (%) x time (s) will be used to
calculate the rSO2 score; from the intraoperative cerebral oximetry data.

Secondary Objective(s):
The secondary objective is to compare the amount of cerebral oxygenation
desaturation episodes (CODE) and their duration. CODE will be defined by a
reduction of 20% baseline value of at least one minute or an absolute reduction
of 50%.
Also, the difference in rSO2 will be assessed at six time points (from a
period of 5 minutes): T1 before induction of general induction of general
anesthesia; T2 after induction of general anesthesia when vital signs are
stable; T3 after initiation CPB; T4 after cross clamping the aorta; T5 after
removal of cross-clamp; T6 after weaning of CPB.
Furthermore, cognition will be evaluated at baseline (one day preoperatively),
three and six months after randomization by the Subjective Cognitive Failure
Questionnaire (CFQ).
As secondary objective, Hematocrit (Ht) during CPB, haemoglobin level (Hb)
during CPB, fluid balance, administration of vasoactive drugs, surgical
re-explorations, length of intensive care unit (ICU) stay, time to detubation,
mixed venous oxygen saturation (sVO2) during CPB, and postoperative
neurological events will be compared.

Design of the study is a Randomized Controlled Trial. By means of a
computer-generator 1:1 randomization table, subjects will be divided in the RAP
group or the Control group. In the RAP group, the patient*s own circulating
blood will partially replace the priming solution in the CPB (which can be
exactly measured). In the Control group the conventional priming method will be
used.

The subjects who are divided in the RAP group, the retrograde autologous
priming technique will be used, where the patient*s own circulating blood
partially will be replaced by the priming solution in the CPB. In the Control
group the conventional priming method will be used.
The RAP method is based on the study of Hwang et al. In RAP, the priming
solution is partially replaced by the patient*s own circulating blood, before
initiation of CPB. After arterial cannulation of the aorta ascendens (DLP®
arterial cannula straight or curved, Medtronic Inc®, Minneapolis, MN, USA) the
priming volume in the arterial line is replaced by the patient*s own blood
through gravity drainage, the priming solution is pushed in a blood transfer
bag. After venous cannulation (Dual-stage venous drainage cannula 36/51 fr,
Medtronic Inc® MC2) a clamp is placed on the arterial line. After starting
venous drainage, the priming volume of the venous line is pumped into the blood
transfer bag and replaced by patient*s own blood. When approximately 400 ml of
priming volume is displaced into the bag, the line to the bag will be closed
and the clamp will be removed from the arterial line. Thereafter, de
cardiopulmonary bypass is started. After initiation of cardiopulmonary bypass
the priming volume is approximately 900 ml.
In case of the conventional priming method, the priming volume of the arterial
and venous line will not be replaced by patient*s own blood. The priming volume
of cardiopulmonary bypass is 1300 ml in the conventional method

As there are no risks involved there will be no intermediate security check.