Extracorporeal Cytokine Adsorption in Cardiac Surgery

Summary

The modern era of cardiac surgery began in early 1950s with the introduction of cardiopulmonary bypass (CPB). Although it has been clearly shown that CPB is almost unavoidable for most open heart operations, an undesirable systemic inflammatory response syndrome (SIRS) is associated with its use. This complex chain of events has strong similarities with sepsis and may contribute to the development of postoperative complications and multiple organ failure (MOF). It has been shown that an excessive compensatory anti-inflammatory response (CARS) after SIRS can lead to immune paralysis and increased rate of hospital acquired infection. The balance of pro-inflammatory and anti-inflammatory mediators determines the inflammatory response and the clinical outcome. Accordingly, great efforts have been focused on therapeutic interventions aimed at reducing the inflammatory reactions during CPB, including pharmacologic strategies and modification of surgical techniques or mechanical devices. Such therapies may provide improvements in patient outcome after open heart operations. Among pharmacologic strategies is the prophylaxis with corticosteroids, which have been used during open heart surgery for more than 30 years. Many studies, both experimental and clinical, failed to produce evidence in favor of steroid treatment. As far as medical devices are concerned, the use of extracorporeal cytokine filter CytoSorb looks promising in cardiac surgery. It was recently approved by European Medicines Agency as an active treatment to fight cytokine storm.

Serum paraoxonase 1 (PON1) is a lipo-lactonase, being associated with HDL that has an anti-inflammatory role and protects against atherosclerosis. Low levels of PON1 are associated with venous graft occlusion in patients with coronary artery bypass grafting. PON1 reduces monocyte chemotaxis and adhesion to endothelial cells, leading to inhibition of the differentiation of monocytes into macrophages. The effects of cytokine adsorption therapy on PON1 are unknown.

The aim of the study is to explore the effects of extracorporeal immunoadsorption during CPB on pro-inflammatory and anti-inflammatory protective mediators and cellular immune status in cardiac surgery.

Conditions

• Cardiopulmonary Bypass

Interventions

DEVICE

CytoSorb

CytoSorb is a first-in-class extracorporeal cytokine adsorber, now approved in the European Union, and broadly indicated for use in any clinical situation where cytokines are elevated.

DRUG

Methylprednisolone

Sponsors & Collaborators

• Slovenian Research Agency

  collaborator OTHER

• University Medical Centre Ljubljana

  lead OTHER

Principal Investigators

• Maja Sostaric, MD, PhD · University Medical Centre Ljubljana

• Matej Podbregar, MD, PhD · University Medical Centre Ljubljana

• Gordana Taleska, MD, MSc · University Medical Centre Ljubljana

• Tomislav Klokocovnik, MD, PhD · University Medical Centre Ljubljana

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-02-01

Primary Completion

2017-12-31

Completion

2018-06-30

Countries

• Slovenia

Study Locations