Immunmodulatorische Aspekte bei der Entstehung, Prophylaxe und Therapie des postoperativen Ileus

Zusammenfassung

Der postoperative Ileus (POI) ist definiert als ein vorübergehender Stillstand der koordinierten Darmperistaltik nach operativen Eingriffen, der eine ausreichende Passage des Darminhalts bzw. die Toleranz der oralen Nahrungsaufnahme verhindert. Dieses häufige Krankheitsbild ist verbunden mit einem Anstieg der perioperativen Morbidität, einer Verlängerung der Krankenhausverweildauer und einer Erhöhung der Kosten. Die Pathogenese des POI ist multifaktoriell: Neben einer Peristaltikhemmung durch inhibitorische neuronale Reflexbögen und der Gabe von Opioiden spielen, insbesondere bei der protrahierten und über Tage andauernden Form, immunologische Mechanismen eine entscheidende Rolle. Hierbei kommt es durch das chirurgische Trauma zu einer Aktivierung von residenten Makrophagen der Tunica muscularis (ME), was letztlich zu einer Freisetzung von proinflammatorischen Mediatoren und einer Ausbreitung der Entzündung auf den gesamten Gastrointestinaltrakt führt. Bis heute existieren weder eine Prophylaxe noch eine evidenzbasierte Therapie. Da die gängigen Konzepte (z. B. die Gabe von Prokinetika) in randomisierten Studien keinen signifikanten Vorteil erbringen konnten, erscheint nach aktueller Datenlage das frühe Eingreifen in die immunologischen Prozesse eine erfolgversprechende Option zur Prophylaxe des POI zu sein. Ziel dieses Manuskripts ist es, eine Übersicht über die dem POI zugrunde liegenden immunologischen Prozesse zu verfassen und nachfolgend einen Fokus auf aktuelle Therapiemaßnahmen und zukünftige potenzielle Optionen der Prophylaxe des POIs zu setzen.

Abstract

Postoperative ileus (POI) is defined as a transient episode of impaired gastrointestinal motility after abdominal surgery, which prevents effective transit of intestinal contents or tolerance of oral intake. This frequent postoperative complication is accompanied by a considerable increase in morbidity and hospitalisation costs. The aetiology of POI is multifactorial. Besides a suppression of peristalsis by inhibitory neuronal signalling and administration of opioids, particularly in the prolonged form, immunological processes play an important role. After surgical trauma, resident macrophages of the muscularis externa (ME) are activated leading to the liberation of proinflammatory mediators and a spreading of the inflammation along the entire gastrointestinal tract. To date, no prophylaxis or evidence-based single approach exists to treat POI. Since none of the current treatment approaches (i.e., prokinetic drug treatment) has provided a benefit in randomised trials, immunoregulatory interventions appear to be more promising in POI prevention or treatment. The present contribution gives an overview of immunological mechanisms leading to POI focusing on current and future therapeutic and prophylactic approaches.

Schlüsselwörter

chirurgische Forschung - experimentelle Chirurgie - Fast-Track-Rehabilitation - Komplikation - postoperativer Ileus - Muscularis externa

Key words

surgical research - experimental surgery - fast-track rehabilitation - complication - postoperative ileus - muscularis externa

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