Is there an improvement of microcirculation regarding propofol vs. sevoflurane anaesthetic regimen during coronary artery bypass grafting?

In general, anesthesia is conducted with intravenous agents or with volatile
agents which are delivered by inhalation. Each way has its advantage, as for
example volatile agents are usually administered to paediatric patients to
prevent mental distress by placing an intravenous line.
The purpose of this study is to investigate whether administration of
sevoflurane during coronary artery bypass grafting (CABG) will improve the
microcirculation when compared to propofol. Recent studies have emphasized that
halogenated volatile anesthetic agents, including sevoflurane (Sevorane®,
Abbott, Hoofddorp, The Netherlands), exert cardioprotective effects by means of
ischemic preconditioning (IPC)1-11. This reduces both the incidence of ischemia
and myocardial infarction size. In addition to the preconditioning effect,
volatile anesthetics suppress neutrophil-endothelium interaction and reduce the
inflammatory response after cardiopulmonary bypass (CPB)12,13,14,15 . Recent
studies show lower postoperative release of troponin I and an improvement of
cardiac output (CO) compared to patients receiving propofol for the same
procedure.10,11,16 Whether changes in the inflammatory response are solely
responsible for the difference observed between propofol and sevoflurane
remains unclear. Moreover, whether the microcirculation is changed during
sevoflurane regimen and whether this is a direct influence or a result of a
blunted inflammatory response, is our study of interest.
This study is an observational study. Our purpose is not to explain the
possible mechanism between inflammatory factors, microcirculation and
sevoflurane or propofol.

1.) First, we hypothesize that a reduction of myocardial damage explained by
lower levels of myocardial damage markers (e.g. troponin I, CK-MB) by
sevoflurane may be related to a reduction of inflammatory mediators (i.e.
TNF-α, CD11b/CD18 cells, and IL-6), which in turn may result in better
haemodynamic parameters (e.g. CO, stroke volume and CI)
2.) Second hypothesis is to ascertain the changes of the microcirculation with
the orthogonal polarization spectroscopy17 (OPS) (Cytometrics, Philadelphia,
USA) imaging device (see below) between sevoflurane and propofol.
3.) The third hypothesis is that a reduced inflammatory response to CPB with
sevoflurane will attenuate the generation of cytokines or reduce activation of
inflammatory cells explained by a reduction in the generation of TNF-α,
CD11b/CD18 cells, and IL-6. Attenuation of the inflammatory response by
sevoflurane may be translated in an improved microcirculation (as measured by
the OPS device, see below) compared to patients with a propofol regimen.

This study is a prospective singe-blinded randomised trial. Patients who are
scheduled to undergo elective CABG will be included. Approval of the study by
the hospital*s Medical Ethics Committee (St. Antonius hospital, Nieuwegein, The
Netherlands) is a pre-requisite. When approved, informed consent will be
obtained and adult patients undergoing CABG will be identified by a study-code.
The patients will be randomised to either the propofol or sevoflurane group,
meaning that after induction of anesthesia, throughout the procedure only
sevoflurane or propofol will be administered. Both agents are used as
anesthetic in our clinic for this procedure as local custom. The CABG will be
carried out routinely as planned. Fifty patients in total will be studied
At the end of the procedure, when transporting the patient to the ICU, propofol
continuous infusion will be administered as routine. On the ICU, propofol
infusion is applied until the patient is weaned from the ventilation.
When possible, operation and intensive care personnel will be blinded for
randomisation. It is however inevitable that the attending anaesthesiologist
cannot be blinded for administration of either sevoflurane or propofol. The
investigator who records the microcirculation cannot be blinded as well.
Therefore this is a single blinded study. Three images per imaging moment will
be recorded on digital videotape and analysed afterwards using a
semi-quantitative method19 for analysis of Microcirculatory Flow Index (MFI).
The device is gently applied without pressure on the lateral side under the
tongue after removal of saliva. Minimum duration of the images is 20 seconds.
For each measurement a new cap will be used over the lens for the sake of
hygiene. Subsequently, the images are captured in 5 to 10 seconds
representative video clips in AVI format. These video clips are analysed
blindly (by a different investigator) and at random to prevent coupling between
images. To score the MFI, two blinded investigators will asses the MFI
independently and the mean MFI will be used as the definitive score for that
particular image.

Linkage with the patient*s identity will only be possible by the researchers.
Patient*s identity will be handled discretely and patient*s data will be coded.
Published data will have no link with patient identity.
A pulmonary artery catheter (PAC) for measuring haemodynamic data will be
inserted. This is a world-wide routine procedure for patients undergoing
cardiac surgery, though in our hospital we do not insert a PAC for an elective
CABG, since we believe there are no additional advantages.
Also, extra blood samples will be taken to asses biochemical parameters (see
below). Assessments of microcirculation will be performed as described above.
Discomfort for the patients are extra blood samples, risks associated with
introduction and use of pulmonary artery catheter and OPS imaging (however,
most images will be taken when patients are anesthesized).
Patients will be able to stop their participation in this study at any time
they wish without consequences. Collected data at various intervals is
described below.

In accordance with Dutch law, an insurance policy covering all participating
patients has been effected with Medirisk insurance company. Since both propofol
and sevoflurane anesthesia are world wide used for providing anesthesia, no
extra risks are associated concerning anesthesia. OPS imaging performed
sublingually is a non invasive tool as described, thus no additional risks are
provided.
Patients participating in this study will receive a pulmonary artery catheter
in order to asses the haemodynamic parameters. Associated risks are
arrhythmias, ventricular fibrillation, right bundle branch block, complete
heart block, thromboembolism, pulmonary infarction, pulmonary artery rupture,
pulmonary artery pseudoaneurysm, endocardial damage, cardiac valve injury and
endocarditis.21 Furthermore, extra blood samples (maximal 100 ml) as described
above will be taken from patients participating in this study.