Optimal cerebral perfusion after an extracranial-intracranial bypass: should we increase blood pressure or cardiac output?

In patients undergoing surgical cerebral revascularization with a bypass, the
brain is at risk of ischemia. It is of great importance to maintain adequate
cerebral tissue perfusion. Currently, emphasis is placed on blood pressure
ranges to maintain tissue perfusion: high blood pressure levels are realized
using vasopressors, but does this ensure adequate cerebral perfusion, since
perfusion does not only depend on perfusion pressure but also on cardiac
output? We hypothesize that cardiac output rather than blood pressure is
essential for adequate cerebral perfusion during and after cerebral
revascularization.

We aim to study what the mean change in graft flow rate is when the cardiac
output is increased with 10% and what the mean change in graft flow rate is,
when the blood pressure is increased with 10% to enable further research to
establish whether an increase in cardiac output results in a higher graft
perfusion than an increase in blood pressure in patients undergoing cerebral
revascularization surgery with a bypass.

A randomized cross-over pilot study where patients randomly and sequentially
receive dobutamine to increase cardiac output, and phenylephrine to increase
blood pressure. Graft perfusion is measured with an ultrasonographic flow meter
placed on top of the graft.

Patients will receive, randomly and sequentially, dobutamine (2-15 µg/kg/min)
to increase the cardiac output and phenylephrine (0.15-1 µg/kg/min) to increase
the blood pressure.

The burden and risks of this study are negligible. This study will take place
during the hemostasis phase of bypass surgery and does not significantly
increase the length of the procedure and exposure to general anesthesia. Both
phenylephrine and dobutamine are commonly and safely used in anesthetized and
critically ill patients to maintain hemodynamic paramaters within a normal
physiological range. Both drugs have a short duration of action and potential
side-effects disappear within minutes after discontinuation. Routine
hemodynamic monitoring, including 5-leads electrocardiogram and invasive blood
pressure measurements will be used to titrate the dosage and to detect
potential side-effects at an early stage. No further postoperative follow-up is
required for this study. Although both drugs may increase the oxygen
consumption of the myocardium, these effects are limited at the proposed
dosages. Still, as a precaution, patients with a history of a recent
myocardial infarction (<30 days), unstable angina, severe hyperthyroidism,
severe, untreated, ventricular arrhythmia's, hypersensitivity to dobutamine or
phenylephrine, hypertrophic cardiomyopathy and obstruction of the left
ventricular outflow tract will be excluded. As an additional precaution,
patients with a mean arterial blood pressure < 60 mmHg and/or a systolic blood
pressure > 180 mmHg prior to start of one of the interventions will be
excluded.