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DOI: 10.1055/s-2008-1027720
© Georg Thieme Verlag KG Stuttgart · New York
Neues aus der Cochrane Library: µ-Opioidantagonisten für die Behandlung der opioidinduzierten Magen-Darm-Störungen
News from the Cochrane Library: µ-opioid Antagonists for Opioid-Induced Bowel DysfunctionPublikationsverlauf
Manuskript eingetroffen: 10.7.2008
Manuskript akzeptiert: 21.7.2008
Publikationsdatum:
22. September 2008 (online)

Zusammenfassung
Obstipation und andere Magen-Darm-Störungen stellen eine häufige Nebenwirkung einer kurzfristigen postoperativen oder auch chronischen Opioidtherapie dar. Zur Bedeutung von µ-Opioidantagonisten zur Vermeidung bzw. Behandlung dieser Komplikationen konnten die Review-Autoren 23 Studien identifizieren. Die Datenlage zur Sicherheit und Wirksamkeit der traditionellen Antagonisten wie Naloxon oder Nalbuphin ist unzureichend. Die Ergebnisse der Studien zu den neueren, selektiv peripher-wirksamen Antagonisten Alvimopan bzw. Methylnaltrexon sind vielversprechend. Durch Methylnaltrexon konnte in vier Studien an gesunden Probanden eine signifikante Verkürzung der gastrointestinalen Passagezeit um 52 min erreicht werden. Für Alvimopan konnte in fünf Studien eine signifikante Verbesserung der Hazard Ratio’s für unterschiedliche Endpunkte (Stuhlabgang, Verträglichkeit fester Nahrung) im postoperativen Setting gezeigt werden. Es bleibt abzuwarten, inwieweit sich diese Ergebnisse an verschiedenen Patientengruppen im größeren Umfang reproduzieren lassen. Auch steht die Einordnung dieser noch nicht zugelassenen Medikamente insbesondere im Hinblick auf andere pharmakologische (z. B. Lactulose) und nicht pharmakologische Interventionen aus.
Abstract
Constipation and other gastrointestinal symptoms are frequent adverse effects of either short-term postoperative or chronic opioid therapy. The review authors have identified 23 studies to evaluate the efficacy of µ-opioid antagonists for the prevention and treatment of these complications. The data on safety and efficacy of the traditional antagonists naloxone and nalbuphine are insufficient. The results of studies with the newer, peripherally-acting antagonists alvimopan and methylnaltrexone are promising. Methylnaltrexone resulted in four studies with healthy probands in a significant shortening of the gastrointestinal transit time (-52 min). In the postoperative setting, five studies showed a significant improvement of the hazard ratios for different outcomes (e. g., bowel movement, tolerance of solid food) in the alvimopan group. Future studies will be needed to show whether these results can be reproduced in different patient groups on a larger scale. Also, with regard to other pharmacological (e. g., lactulose) and non-pharmacological interventions, the role of the above-mentioned not yet approved medications needs to be defined.
Schlüsselwörter
Cochrane Library - Metaanalyse - systematische Übersichtsarbeit - µ-Opioidantagonisten - opioidinduzierte Magen-Darm-Störungen
Key words
Cochrane Library - meta-analysis - systematic review - µ-opioid antagonists - opioid-induced bowel dysfunction
Literatur
- 1 McNicol E D, Boyce D, Schumann R. et al .Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database of Systematic Reviews: Reviews. Cochrane Database of Systematic
Reviews 2008 Chichester (UK); John Wiley & Sons 2008 Issue 2
MissingFormLabel
- 2
Jadad A R, Moore R A, Carroll D. et al .
Assessing the quality of reports of randomized clinical trials: is blinding necessary?.
Control Clin Trials.
1996;
17
1-12
MissingFormLabel
- 3
Yuan C S, Foss J F, O’Connor M. et al .
Methylnaltrexone prevents morphine-induced delay in oral-cecal transit time without
affecting analgesia: a double-blind randomized placebo-controlled trial.
Clin Pharmacol Ther.
1996;
59
469-475
MissingFormLabel
- 4
Yuan C S, Foss J F, Osinski J. et al .
The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay
in oral-cecal transit time.
Clin Pharmacol Ther.
1997;
61
467-475
MissingFormLabel
- 5
Yuan C S, Foss J F, O’Connor M. et al .
Effects of enteric-coated methylnaltrexone in preventing opioid-induced delay in oral-cecal
transit time.
Clin Pharmacol Ther.
2000;
67
398-404
MissingFormLabel
- 6
Yuan C S, Wei G, Foss J F. et al .
Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated
side effects: a double-blind randomized placebo-controlled trial.
J Pharmacol Exp Ther.
2002;
300
118-123
MissingFormLabel
- 7
Liu S S, Hodgson P S, Carpenter R L. et al .
ADL 8 – 2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal
effects of intravenous morphine without affecting analgesia.
Clin Pharmacol Ther.
2001;
69
66-71
MissingFormLabel
- 8
Yuan C S, Foss J F, O’Connor M. et al .
Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized
controlled trial.
JAMA.
2000;
283
367-372
MissingFormLabel
- 9
Delaney C P, Weese J L, Hyman N H. et al .
Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist,
for postoperative ileus after major abdominal surgery.
Dis Colon Rectum.
2005;
48
1114-1125
MissingFormLabel
- 10
Herzog T J, Coleman R L, Guerrieri J P. et al .
A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan
in patients who undergo simple total abdominal hysterectomy.
Am J Obstet Gynecol.
2006;
195
445-453
MissingFormLabel
- 11
Taguchi Jr A, Sharma N, Saleem R M. et al .
Selective postoperative inhibition of gastrointestinal opioid receptors.
N Engl J Med.
2001;
345
935-940
MissingFormLabel
- 12
Viscusi E R, Goldstein S, Witkowski T. et al .
Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo
in postoperative ileus after major abdominal surgery: results of a randomized, double-blind,
controlled study.
Surg Endosc.
2006;
20
64-70
MissingFormLabel
- 13
Wolff B G, Michelassi F, Gerkin T M. et al .
Alvimopan, a novel, peripherally acting mu opioid antagonist: results of a multicenter,
randomized, double-blind, placebo-controlled, phase III trial of major abdominal surgery
and postoperative ileus.
Ann Surg.
2004;
240
728-734
MissingFormLabel
- 14
Paulson D M, Kennedy D T, Donovick R A. et al .
Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment
of opioid-induced bowel dysfunction – a 21-day treatment-randomized clinical trial.
J Pain.
2005;
6
184-192
MissingFormLabel
- 15
Liu M, Wittbrodt E.
Low-dose oral naloxone reverses opioid-induced constipation and analgesia.
J Pain Symptom Manage.
2002;
23
48-53
MissingFormLabel
- 16
Sykes N P.
An investigation of the ability of oral naloxone to correct opioid-related constipation
in patients with advanced cancer.
Palliat Med.
1996;
10
135-144
MissingFormLabel
- 17
Barr W H, Nguyen P, Slattery M. et al .
ADL 8 – 2698 reverses opioid induced delay in colonic transit.
Clin Pharmacol Ther.
2000;
67
91
MissingFormLabel
- 18
Freye E, Helle G.
The agonist-antagonist nalbuphine prolongs gastro-cecal transit time and induces short-term
pain following neuroleptanesthesia using fentanyl. A comparative study using a placebo.
Anaesthesist.
1988;
37
440-445
MissingFormLabel
- 19
Gonenne J, Camilleri M, Ferber I. et al .
Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled
study.
Clin Gastroenterol Hepatol.
2005;
3
784-791
MissingFormLabel
- 20
Hawkes N D, Richardson C, Evans B K. et al .
Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers
taking codeine.
Aliment Pharmacol Ther.
2001;
15
625-630
MissingFormLabel
- 21
Lee J, Shim J Y, Choi J H. et al .
Epidural naloxone reduces intestinal hypomotility but not analgesia of epidural morphine.
Can J Anaesth.
2001;
48
54-58
MissingFormLabel
- 22
Meissner W, Dohrn B, Reinhart K.
Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical
care patients during opioid analgesia.
Crit Care Med.
2003;
31
776-780
MissingFormLabel
- 23
Meissner W, Hartmann M, Kahler G. et al .
Effect of enteral naloxone on the incidence of gastritis and esophagitis in mechanically
ventilated patients.
Anasthesiol Intensivmed Notfallmed Schmerzther.
2004;
39
538-541
MissingFormLabel
- 24
Murphy D B, Sutton J A, Prescott L F. et al .
Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.
Anesthesiology.
1997;
87
765-770
MissingFormLabel
- 25
Nimmo W S, Heading R C, Wilson J. et al .
Reversal of narcotic-induced delay in gastric emptying and paracetamol absorption
by naloxone.
Br Med J.
1979;
2
1189
MissingFormLabel
Dr. Joerg J. Meerpohl
Deutsches Cochrane Zentrum, Institut f. Med. Biometrie u. Med. Informatik, Abteilung
f. Med. Biometrie und Statistik
Stefan-Meier-Str. 26
79104 Freiburg
Telefon: ++ 49/7 61/2 03 66 91
Fax: ++ 49/7 61/2 03 67 12
eMail: meerpohl@cochrane.de