Blood pressure and cardiac output - the influence on cerebral perfusion during cardiopulmonary bypass.

A jeopardized cerebral blood flow (CBF) for a few minutes* results in
irreversible cerebral tissue damage. Therefore, the CBF is autoregulated
implying that CBF remains constant despite changes in cerebral perfusion
pressure. Since the 1970s, Near Infra-Red spectroscopy (NIRS) derived frontal
lobe oxygenation (rSO2) and flow velocity of the middle cerebral artery (Vmca)
measured by transcranial doppler (TCD) can be used continuously and
non-invasively, as a derivative for CBF. These monitoring techniques are used
extensively and in the case of a decreasing rSO2, various algorithms have been
proposed to optimize rSO2. One of the first steps in the algorithm is to
increase blood pressure by administrating an *1*receptor mediated vasopressor
like phenylephrine. However, several studies recently described that the rSO2
decreased after phenylephrine administration. It remains unknown why rSO2
decreased, but it could be a result of the *1*receptor mediated decline in
cardiac output (CO). This hypothesis is supported by the finding that in
patients on CardioPulmonary Bypass (CPB), i.e. with constant Cardiac Output
(CO), the rSO2 only decreased with 3% after administering phenylephrine in
comparison to a 10% decline in rSO2 in non-cardiac surgery. It therefore still
remains unclear whether rSO2 is (more) dependent on blood pressure or on CO.
Our aim is to determine whether cerebral blood flow and cerebral tissue
oxygenation is most dependent on cardiac output or on mean arterial pressure in
patients undergoing cardiac surgery with the use of CPB.

To study the influence of systemic blood flow and mean arterial pressure on
cerebral blood flow and cerebral tissue oxygenation in patients undergoing
on-pump cardiac surgery.

This is a randomised cross-over study.

Interventions pre-cardiopulmonary bypass
(1) Determination of changes in cerebral tissue oxygenation and cerebral blood
flow when both blood pressure and blood flow can vary.

In this intervention we will administer 50-100 *g phenylephrine to the patient
before CPB is started. This intervention will take place when the patient shows
hypotension (MAP <60mmHg, according to protocol22). Administering phenylephrine
will increase the MAP by increasing Peripheral Vascular Resistance (PVR).
Because of the increase in PVR there will be a baroreceptor-reflex-mediated
decrease in CO. On-line, we will quantify the percentage decrease in systemic
blood flow (i.e. CO) by using the Modelflow algoritm incorporated in a
non-invasive beat-to-beat finger blood pressure monitor. This will allow us to
obtain a reference for the decrease in CO to use in the next interventions. Our
hypothesis is that CO will decrease because of the baroreceptor-reflex18,19.

Interventions during cardiopulmonary bypass
(2) Determination of changes in cerebral tissue oxygenation and cerebral blood
flow when only systemic blood pressure is varied.

In this intervention we will induce only 1 component of the changes at
intervention (1), being the increase in MAP of approximately 20 mmHg by
administrating 50-100 *g phenylephrine. The CPB enables us to maintain a
constant CO and thus eliminating the baroreceptor-reflex.

(3) Determination of changes in cerebral tissue oxygenation and cerebral blood
flow when only systemic blood flow is varied.

With this intervention we will only create a change in CO, which enables us to
eliminate the effect of blood pressure. We will modify CPB flow to achieve the
CO decrease (in %) measured at intervention (1) meaning: pre-CPB after the
bolus of 50-100 *g phenylephrine. In the case of unexpected increase (in %) of
CO measured at intervention (1), we will still decrease CPB flow so we will be
able to analyse decrease as well as increase in CPB flow.

(4) Determination of changes in cerebral tissue oxygenation and cerebral blood
flow when both the systemic blood pressure and the CO are varied as observed
during intervention (1).

In this intervention we will simulate the *normal* physiological state when
administering phenylephrine. We will modify CPB flow to achieve the percentage
change CO as observed during intervention (1) as well as administrate 50-100 *g
phenylephrine. We expect to see similar outcomes as in intervention (1).

(5) Determination of changes in cerebral tissue oxygenation and cerebral blood
flow when CPB flow is raised.

In this last intervention we will create an increase in MAP without using
phenylephrine but only by increasing CO. This enables us to eliminate a
possible direct *1-adrenergic effect on the cerebral vasculature. MAP will be
raised approximately 20 mmHg by increasing CPB flow 20%.

The burden and risks of participating in this study are negligible because all
modifications will be in the physiological range. Phenylephrine used in this
study will be used within its indication. There will be no time burden since
all the investigations can be done just before and during cardiopulmonary
bypass. There will be no follow up.