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Ist die pharmakologische Therapie der Obstipation in der Palliativmedizin evidenzbasiert?

Eine systematische Literaturübersicht

Is the pharmacological treatment of constipation in palliative care evidence based?

A systematic literature review

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Zusammenfassung

Material und Methoden

Zur Untersuchung der Evidenz klinisch etablierter Therapien zur medikamentösen Behandlung der Obstipation bei palliativmedizinischen Patienten wurde eine systematische Literatursuche in unterschiedlichen Datenbanken (Cochrane Library, Embase, PubMed, Ovid MEDLINE, CINAHL) sowie in Literaturangaben von Publikationen und Lehrbüchern durchgeführt.

Ergebnisse

Während zur medikamentösen Therapie der Obstipation bei Patienten, die sich nicht in einer palliativen Situation befinden, z. B. bei einer primären Obstipation, 130 randomisierte, kontrollierte Studien (RCT) gefunden wurden, konnten nur 10 kontrollierte Studien an Patienten in palliativer Situation identifiziert werden: In 3 RCT zu Methylnaltrexon und einer Studie zur Kombination Naloxon/Oxycodon, die in Palliativeinrichtungen durchgeführt wurden, konnte die Wirksamkeit von Opiatantagonisten bei der opioidinduzierten Obstipation bei Patientengruppen gezeigt werden, die kein erhöhtes Risiko für eine gastrointestinale Perforation tragen. Keine Studie prüfte die Anwendung von Opiatantagonisten gegen eine Optimierung der Therapie mit herkömmlichen Laxanzien. In 6 weiteren kontrollierten Studien, deren Aussagekraft aufgrund einer geringen Patientenzahl oder Einschränkungen in Studiendesign und -durchführung stark limitiert ist, wurden Naloxon, Senna, Lactulose, Codanthramer, ein Ayurvedapräparat (Misrakasneham), Magnesiumhydroxid, flüssiges Paraffin, Natriumpicosulfat und Docusat geprüft, ohne statistisch signifikante Unterschiede zwischen diesen Substanzen in Wirkung und Nebenwirkungen nachweisen zu können. Nur 2 Studien über Senna und Lactulose bzw. Senna und Docusat schlossen wenige Patienten mit ein, die keine Opioide einnahmen. Die Mehrzahl der in allen Studien eingeschlossenen Patienten waren Tumorpatienten. Zu Neostigmin, Meglumin und anderen o. g. Substanzen fanden sich für palliativmedizinische Patienten nur einzelne Fallserien.

Schlussfolgerungen

Die studienbasierte Evidenz zur Behandlung der Obstipation bei Patienten in einer palliativen Situation ist somit als gering einzustufen, sodass Therapieempfehlungen in vielen Fällen auf Evidenz aus dem nichtpalliativen Bereich bzw. auf Expertenmeinungen zurückgreifen müssen. Ergebnisse aus Studien mit nichtpalliativmedizinischen Patienten sind nur begrenzt auf die in der Regel polymorbiden Patienten aus der Palliativmedizin übertragbar. Diese Patienten leiden unter einer erhöhten Anfälligkeit für potenzielle Nebenwirkungen, z. B. unter der erhöhten Gefahr für gastrointestinale Perforationen bei abdominalem Tumorbefall. Die begrenzte Datenlage erfordert daher weitere Studien, die den multifaktoriellen Ursachen für Obstipation bei palliativmedizinischen Patienten gerecht werden und ihren Schwerpunkt auf die Lebensqualität und klinische Anwendbarkeit legen.

Abstract

Materials and methods

To evaluate the evidence for clinically established pharmacological therapies for constipation in palliative care, a systematic literature review was performed in different databases (Cochrane Library, Embase, PubMed, Ovid MEDLINE, CINAHL), textbooks, and publications.

Results

Whereas 130 randomized controlled trials were found with patients outside of palliative care settings, only 10 controlled studies with patients in end-of-life situations were identified: three RCTs with methylnaltrexone and one with the combination of oxycodone and naloxone showed the effect and safety of opiate antagonists for patients who are not at risk of gastrointestinal perforation. There have been no studies which test methylnaltrexone against the optimization of therapy with conventional laxatives. Six other controlled studies of limited quality in design and execution and with only few participants tested naloxone, senna, lactulose, Co-danthramer, an Ayurvedic preparation (Misrakasneham), magnesium hydroxide, fluid paraffin, sodium picosulfate and docusate without finding statistically significant differences in efficacy or side effects. Most patients in these studies had cancer. Only case studies with few patients in palliative care were found for meglumine, neostigmine, and other substances mentioned above.

Conclusion

Evidence on medical treatment of constipation in palliative care is sparse and guidelines have to refer to evidence from outside the palliative care setting and to expert opinions. Results from studies with other patient groups can only be transferred with limitations to very ill patients at the end of life who might have a higher risk for potential side effects such as gastrointestinal perforation in case of abdominal tumor manifestation. Therefore further studies are required to evaluate the medical treatment of multiple reasons for constipation in these patients. These studies should focus on feasibility, clinical relevance and quality of life.

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Danksagung

Die Arbeit wurde nach den Vorgaben der Steuerungsgruppe für Therapieempfehlungen Palliativmedizin der Arzneimittelkommission der Deutschen Ärzteschaft (Lukas Radbruch, Friedemann Nauck, Bernd Alt-Epping, Roman Rolke, Mariam Ujeyl, Rainer Lasek) durchgeführt. Wir danken Sabine Buroh, Bibliothekarin am Universitätsklinikum Freiburg, für ihre Hilfe bei der Durchführung der Datenbankrecherchen.

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Bader, S., Weber, M. & Becker, G. Ist die pharmakologische Therapie der Obstipation in der Palliativmedizin evidenzbasiert?. Schmerz 26, 568–586 (2012). https://doi.org/10.1007/s00482-012-1246-1

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