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Einsatz eines Zytokinfilters in die Herz-Lungen-Maschine

Modifikation der postoperativen Entzündungsreaktion

Use of cytokine filters in cardiopulmonary bypass machines

Modification of postoperative inflammatory responses

  • Kardiotechnik/EKZ
  • Published:
Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Hintergrund

Herzchirurgische Eingriffe mit der Herz-Lungen-Maschine (HLM) induzieren durch die Aktivierung multipler Entzündungskaskaden eine systemische Entzündungsreaktion. Diese kann in der postoperativen Phase das systemische inflammatorische Response-Syndrom (SIRS) auslösen. Die Aktivierung verschiedener Entzündungsmediatoren (Interleukin-6 [IL-6], Tumor-Nekrose-Faktor-α [TNF-α] etc.) kann postoperativ zu Komplikationen, Organdysfunktionen, Morbidität und Mortalität führen.

Ziel der Arbeit

Der Effekt der Adsorption von Zytokinen durch CytoSorb® an der HLM bei kardiochirurgischen Eingriffen soll evaluiert werden.

Material und Methode

In 3 Vergleichsgruppen von je 100 Patienten, die sich einer elektiven Myokardrevaskularisation unterziehen, werden insgesamt 300 Patienten verglichen: Myokardrevaskularisation mit Einsatz von HLM und CytoSorb® (Cytosorb-Gruppe), mit Einsatz der HLM („On-pump“-Gruppe) und ohne HLM („Off-pump“-Gruppe). Primärer Studienendpunkt ist die Entzündungsreaktion, gemessen im Serum mithilfe von IL-6, IL-8, TNF-α, C3/C4-Komplement, Leukozytenzahl und C‑reaktivem Protein. Sekundäre Endpunkte sind Dauer des Krankenhaus-/Intensivstationaufenthalts, Beatmungszeit, Dauer der Katecholamintherapie, Nierenfunktionsstörungen sowie „major adverse cardiac and cerebrovascular events“ (MACCE: Mortalität, Myokardinfarkt und zerebrovaskuläre Ereignisse).

Ergebnisse

Eine Interimsanalyse nach 60 % des geplanten Patientenkollektivs zeigt die ausgeglichene Verteilung der Patienten in die Gruppen. In der Cytosorb-Gruppe sind die IL-6-Spiegel reduziert, während die TNF-α-Spiegel vergleichbar sind. Tendenziell scheinen in dieser Gruppe Infektionen seltener aufzutreten.

Schlussfolgerung

Der Filter CytoSorb® ist gegenüber dem Standardverfahren sicher und ohne technische Schwierigkeiten anwendbar. CytoSorb® reduziert die Zytokinlast und scheint die Entzündungsreaktion abzumildern. Erste positive Tendenzen in klinischen Endpunkten müssen in weiteren Studien bestätigt werden.

Abstract

Background

Cardiac surgical interventions using a cardiopulmonary bypass (CPB) machine induce a systemic inflammatory reaction due to activation of multiple inflammatory cascades. In the postoperative phase this can result in systemic inflammatory response syndrome (SIRS). The activation of various mediators of inflammation, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) can lead to postoperative complications, organ dysfunction, morbidity and mortality.

Aim

The effect of adsorption of cytokines using CytoSorb® with a CPB machine during cardiac surgery is evaluated.

Material and methods

This study is being conducted as a prospective, observational pilot study to determine the clinical impact of the use of an adsorption filter (CytoSorb®) on the serum levels of IL-6, IL-8 and TNF-alpha using a CPB machine. This pilot study includes 300 patients planned for elective surgical myocardial revascularization, partitioned into 3 groups each with 100 patients with on-pump myocardial revascularization with CytoSorb®, on-pump myocardial revascularization without CytoSorb® and off-pump myocardial revascularization. Primary outcome measures are the inflammatory response serum parameters IL-6, IL-8, TNF-alpha, complement C3/C4, leucocyte counts and C‑reactive protein. Secondary outcome measures are length of intensive care unit (ICU) and total hospital stay, duration of ventilation, duration of catecholamine therapy, kidney injury as well as major adverse cardiac and cerebrovascular events (MACCE, mortality, myocardial infarction and cerebrovascular events).

Results

An interim analysis after concluding 60 % of the planned patients revealed a well-balanced group allocation of patients. In the group with CytoSorb® the IL-6 values are decreased, whereas TNF-alpha values are comparable between the three groups. There seems to be a tendency for less infections in this group.

Conclusion

The use of the CytoSorb® filter during CPB is safe compared with the standard procedure and applicable without technical difficulties. CytoSorb® reduces the cytokine load and seems to attenuate the inflammatory response. Initial positive tendencies in improved clinical endpoints need to subsequently be confirmed in continuing studies.

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Authors and Affiliations

  1. Klinik und Poliklinik für Herz- und Thoraxchirurgie, Herzzentrum, Uniklinik Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    A.-C. Deppe, C. Weber, Y.-H. Choi & T. Wahlers

  2. Cardiovascular Research Center Cologne, Uniklinik Köln, Köln, Deutschland

    Y.-H. Choi

Authors
  1. A.-C. Deppe
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  2. C. Weber
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  3. Y.-H. Choi
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  4. T. Wahlers
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Corresponding author

Correspondence to A.-C. Deppe.

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Interessenkonflikt

A.-C. Deppe, C. Weber, Y.-H. Choi und T. Wahlers geben an, dass kein Interessenkonflikt besteht.

Alle teilnehmenden Patienten wurden vor Einschluss in die Studie ausführlich aufgeklärt und willigten schriftlich ein. Die Studie wurde von der Ethikkommission der Uniklinik zu Köln genehmigt (13-230) und bei clinical.gov (NCT02213939) registriert. Die Studie wird unter Einhaltung aller geltenden Gesetze GCP konform [14] und den Prinzipien der Deklaration von Helsinki [15] entsprechend durchgeführt.

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Deppe, AC., Weber, C., Choi, YH. et al. Einsatz eines Zytokinfilters in die Herz-Lungen-Maschine. Z Herz- Thorax- Gefäßchir 30, 254–259 (2016). https://doi.org/10.1007/s00398-016-0075-4

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  • DOI: https://doi.org/10.1007/s00398-016-0075-4

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