The effect of haemoadsorption in relation to the cytokine concentration during cardiothoracic surgery procedures while using extracorporeal circulation.

Many attempts have been made to reduce the inflammatory activation during
coronary bypass surgery (CABG procedure) using extracorporeal circulation
(ECC), however without much success.
The inflammatory activation process takes place, both locally in the organs, as
in the systemic circulation. Surgical trauma and the contact of blood with
non-endothelial surfaces such as the heart-lung machine disposables, activates
the cellular and humoral defense mechanism.
In addition, aberrant organ perfusion during ECC, the duration of the ECC and
the restore of normal organ perfusion (ischemia/reperfusion =) after ECC leads
to activation of the humoral and cellular defense mechanism with numerus
pathways. These pathways consist of activation/generation or expression of
thrombin, complement, cytokines, adhesion molecules, mast cells and
neutrophils, different inflammatory mediatore.
Some patients have to deal with organ dysfunction and hemodynamic instability
after ECC.
Inflammatory processes and ischemic-reperfusion injury also triggers the
development of vascular dysfunctions and activation of the complementsystem. As
result pro-and anti-inflammatory mediators (cytokines) wil be released in the
circulation. In the worst case systemic inflammatory syndrome (SIRS) wil be
developed, by initiation of the inflammatory cascades and profound
amplification. The duration of ECC is considered as a risk, but it is not
necessary to develop SIRS.
Complement activation with increased cytokine release in cardio surgery may
also be caused by the following factors:
chronic immune activation (it is associated with atherogenesis and/or
progression of atherosclerosis) whith the inflammatory activation already
activated before the surgical procedure. Patients older (> 65 Jr.) have a
higher complement concentration at the decline of the aortic clamp, by an
increased IL-6 production.
So far one tried a number of methods/techniques to decrease the excessive
release of cytokines related to ECC, namely:
* Cardio surgery procedures without the use of heart-lung machine, but this
also leads to increased release of cytokines and other mediators.
* ECC without cardioplegic arrest.
* Leukocyte filter.
* Administration of corticosteroids.
* Hemofiltatrion strategys such as: Balanced ultrafiltration, high volume
Hemofiltration (HVHF), high cut-off (HCO) Hemofiltration and other
ultrafiltration (UF) techniques related to extracorporeal circulation.

In the fight against excessive cytokine production is the CytoSorb *
haemoadsorber developed. The operation of this haemoadsorber is based on
adsorption of particles with a low molecular weight (5-60 kDa).
Previous study(s) with CytoSorb (at non-homogeneous groups) are promising,
other(s) showed no clinical relevance and the literature does not provide a
consistant start value for the cytokines during ECC. We want to analyze the
effect of the Cytosorb during CABG-surgery and describe the effect on cytokine
level in this pilot study. A pilot study is necessary because it is still
unclear what initial cytokine concentration we may expect.
Depending on the results, the Cytosorb may be used in the future by indication
during heart surgery.

The aim of the study is, to analyze the effect of the haemoadsorption device
Cytosorb in relation to the inflammatory parameters IL-6, IL-8, IL-10,TNF-* and
CRP at six different time points during conventional CABG procedures.
We assess whether the haemoadsorption device Cytosorb can relevantly reduce
cytokine levels to the normal start concentration.

In this single (patient) blind randomized pilot study 30 patients planned for
elective CABG surgery with ECC support will be asked/informed, they will be
included after signing the informed consent.
The subjects are randomized into 2 groups.
* Group 1: CABG group without the haemoadsorber in the ECC circuit: control
group (CECC).
* Group 2: CABG group with the haemoadsorber in the ECC circuit: intervention
group (HECC).

The intervention consists of leading blood through the Cytosorb adsorber the
ECC.
Extend of the research: on arrival at the operating room up to 4 hours post
surgically.
Subject inclusion starts as soon as RTPO approval issued is received. The end
of the study is achieved when data of all 30 subjects is analyzed.

In the intervention group, the haemoadsorber in the extra cannon system behind
the oxygenator. The blood flow over the adsorber is 350-400 ml/min.

During this survey, bloodsamples will be collected according to the schedule
below.
T0: pré anaesthesiological induction
T1: 5 min after start ECC
T2: at 60 min ECC and or slightly before the end of the ECC.
T3: on ICU arrival (aproximately 30 min after surgery)
T4:2 hours after ICU arrival.
T5:4 hours after ICU arrival.

T3, T4 and T5: will be collected according to: the sample protocol at the ICU.

The intervention consists of the leading blood through the Cytosorb adsorber
during CABG-surgery.

The only load for the patient consists of filling the informed consent, this
covers about 15 minutes.
There is no risk of burden with the participation, the entire CABG-procedure
will be performed as normal. The cytokines will not be completely removed but
they will be reduced.
During the investigation bloodsamples will be collected at six times from the
test subjects, this total is less than 60 ml. The bloodsample collection is
chosen simultaneously with the regular blood collection associated with the
surgery. The blood will be collected from a already placed infusion line.
This haemoadsorber adsorbs possibly certain types of antibiotics as with
dialysis or haemofiltration. These are not the antibiotics which are
administered to the test subjects during the standard heart surgery.
There is a possibility of hypersensitivity to (polystyrene / divinylbenzene,
polycarbonate, polypropylene, silicone and polyester). With known
hypersensitivity to these substances, the test subjects will not be included.