Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation

Study Overview
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Brief Summary
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There are several factors initiating cytokine storm and dysregulated systemic inflammatory response during cardiac transplantation. This may lead to serious perioperative complications: circulatory collapse, respiratory insufficiency, acute renal and liver failure, multi-organ dysfunction etc. On the other hand the high level of cytokines may play an important role in the development of graft rejection which is still a relevant problem in this patient group. There are some new data showing that the use of extracorporeal cytokine adsorber during long cardiopulmonary bypass time (>120min) may be beneficial to prevent SIRS (Systemic Inflammatory Response Syndrome) with decreasing the level of cytokines in patients undergoing elective cardiac surgery. However there is lack of data and studies regarding the effect of extracorporeal cytokine adsorption during cardiac transplantation. The aim of the study is to investigate the effect of extracorporeal cytokine adsorber built in the cardiopulmonary bypass circle during heart transplantation. The hypothesis is that removal of cytokines during heart transplantation prevents the development of extreme systemic inflammatory response, hemodynamic collapse dominated by vasoplegia, and contribute to reduce the incidence of severe perioperative complications and early graft rejection.

Detailed Description
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Patients undergoing cardiac transplantation will be enrolled in the study after giving a written, signed informed consent. The participants will be randomized into two groups: intervention group (30 patients): a cytokine adsorber (CytoSorb®) will be installed into the cardiopulmonary bypass circle during the operation control group (30 patients): no cytokine adsorber will be used during cardiopulmonary bypass The investigators will collect demographic, clinical and laboratory data about patients before, during and after the operation. The the use of vasopressors and inotropes in the perioperative period, length of mechanical ventilation, ICU and hospital stay, and incidence of perioperative complications, early cellular or humoral graft rejection, and survival will be documented. The level of cytokines (IL-1, IL-6, IL-10, IL-17, tumor necrosis factor-alfa) and complements before, during and after the use of cardiopulmonary bypass will be determined if the investigators find relevant difference between the two groups in clinical variables.

Official Title
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The Impact of Pre-emptive Intraoperative Use of Extracorporeal Cytokine Adsorption During Orthotopic Heart Transplantation

Conditions
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Cardiac Transplantation, Cardiopulmonary Bypass

Intervention / Treatment
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* Device: CytoSorb®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients undergoing heart transplantation no medical or mechanical circulatory support straight before transplantation age > 18 years Exclusion Criteria: age < 18 years septic condition (controlled infection) before transplantation prolonged hospital stay straight before transplantation use of positive inotropes or vasopressors straight before transplantation use of mechanical circulatory support straight before transplantation acute liver or kidney failure straight before transplantation high urgency transplantation retransplantation the patient declines participating in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CytoSorb®<br>The CytoSorb® filter will be installed into the cardiopulmonary bypass circle during cardiac transplantation in this study group (30 patients) | Device: CytoSorb®<br>* CytoSorb® is a biocompatible, high adsorptive polymer indicated in conditions where cytokine levels are extremely elevated.<br>|
| No Intervention: Control<br>No filter will be installed into the cardiopulmonary bypass circle in this group (30 patients). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early postoperative hemodynamic instability | Hemodynamic instability described by Vasoactive Inotropic Score and calculated for the first two postoperative days. Vasoactive Inotropic Score is considered as 'high' if values ≥ 30 points, representing higher risk for worse outcomes. | 24-48 hours | 
| Postoperative vasoplegia syndrome | Severity of postoperative vasoplegia based on criteria of vasoplegia syndrome: Norepinephrine reqirements ≥ 0.3 μg/kg/min AND arginine vasopressin requirements at any dose | 24-48 hours | 
| Cytokine and complement levels | Level of pro- and anti-inflammatory cytokines (IL-1, IL-6, IL-10, IL-17, tumor necrosis factor-alfa) and complements immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB | 24-48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory reaction | Level of C reactive protein (CRP), white blood cells and procalcitonin immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB | 24-48 hours | 
| Mechanical ventilation | Length of mechanical ventilation | up to 6 months | 
| Hospital stay | Length of ICU and hospital stay | up to 6 months | 
| Length of survival | Length of survival after heart transplantation | 1 year | 
| Medical circulatory support | Use and dosage of vasopressors and inotropes immediately after induction of anesthesia, before initiation of cardiopulmonary bypass (CPB), 2 hours after initiation of CPB, at termination of CPB, 6-12-24 hours after initiation of CPB, on 2nd and 3rd postoperative day | 72 hours | 
| Perioperative complications | Incidence of perioperative complications after heart transplantation during ICU stay (sepsis, SIRS, respiratory failure, acute renal failure, acute liver failure, postoperative cognitive dysfunction, graft failure) | up to 1 month | 
| The incidence of early rejection | The incidence of early (< 1 month) cellular or humoral rejection after heart transplantation | 1 month |